hirudin and Hemorrhage

Bivalirudin has been suggested as an alternative to heparin for anticoagulation in patients receiving extracorporeal membrane oxygenation (ECMO). Nevertheless, there is limited evidence about the benefit of bivalirudin in ECMO patients compared with heparin. Hence, we conducted a meta-analysis to assess the effect of bivalirudin versus heparin on clinical outcomes in patients receiving ECMO.. PubMed, Embase, and the Cochrane Library were systematically searched from inception up to 1 April 2022 for cohort studies and randomized controlled trials comparing bivalirudin versus heparin in patients who received ECMO. The primary outcome was short-term death. Secondary outcomes included thrombotic events and bleeding events.. We selected 12 retrospective cohort studies with 1232 ECMO patients focusing on bivalirudin anticoagulation (n = 497) versus heparin anticoagulation (n = 735). Two hundred and one of 497 patients (40.4%) in the bivalirudin group versus 350 of 735 patients (47.6%) in the heparin group did not survive to hospital discharge. Compared with the heparin group, bivalirudin anticoagulation did not significantly decrease in-hospital mortality in patients receiving ECMO (RR, 0.95; 95% CI, 0.79-1.13;. Compared with heparin anticoagulation, bivalirudin did not decrease the rates of short-term mortality and thrombotic events, but reduced the incidence of bleeding events in patients receiving ECMO.

Topics: Anticoagulants; Extracorporeal Membrane Oxygenation; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombosis

The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI.. We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding.. In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombosis; Treatment Outcome

Our study sought to investigate the efficacy and safety of bivalirudin versus those of unfractionated heparin (UFH) in patients undergoing extracorporeal membrane oxygenation (ECMO).. PubMed, EMBASE and Cochrane Library were searched for studies enrolling ECMO patients on bivalirudin and UFH (from inception till July 2021). Meta-analysis was conducted. The I. Fourteen eligible retrospective observational studies with 1501 subjects were identified. Compared with UFH, bivalirudin significantly reduced the risk of in-circuit thrombosis (OR = 0.44, 95% CI [0.31-0.61], p = 0.000), thrombosis (OR = 0.61, 95% CI [0.45-0.83], p= 0.002) and hospital mortality (OR = 0.78, 95% CI [0.61-0.99], p = 0.04) and had a positive impact on survival ECMO (OR = 1.50, 95% CI [1.04-2.16], p= 0.032). Decrease in risk of bleeding (OR = 0.36, 95% CI [0.14-0.91], p = 0.031) associated with bivalirudin was observed. Sources of heterogeneity were identified, and sensitivity analysis revealed similar results.. Our meta-analysis suggested that bivalirudin was associated with the decreased risk of in-circuit thrombosis, thrombosis, hospital mortality and bleeding in patients on ECMO and improved survival ECMO, indicating the superiority of bivalirudin to UFH in terms of efficacy and safety.

Topics: Adult; Anticoagulants; Child; Extracorporeal Membrane Oxygenation; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombosis; Treatment Outcome

Bivalirudin and heparin are the principal anticoagulants used during primary percutaneous coronary intervention (PCI) for patients experiencing ST-elevation myocardial infarctions. Based on previous meta-analyses, bivalirudin improves 30-day mortality rates compared with heparin, especially when vascular access is predominantly femoral. However, no meta-analysis has yet reported whether this mortality benefit with bivalirudin persists beyond 30 days. Scientific databases and websites were searched to find randomized controlled trials, and risk ratios (RRs) were calculated using random effect models. Data from 4 trials were analyzed. Compared with heparin ± glycoprotein IIb/IIIa inhibitors, bivalirudin decreased all-cause mortality [RR, 0.81; 95% confidence interval (CI), 0.69-0.94; P = 0.008], cardiac mortality (RR, 0.72; 95% CI, 0.60-0.88; P = 0.001), and net adverse clinical events (RR, 0.83; 95% CI, 0.72-0.97; P = 0.016) at 1 year. In conclusion, a bivalirudin-based anticoagulation strategy during primary percutaneous coronary intervention significantly decreases the 1-year risks for all-cause mortality, cardiac mortality, and net adverse clinical events compared with heparin ± glycoprotein IIb/IIIa inhibitor.

Topics: Antithrombins; Evidence-Based Medicine; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome

This meta-analysis was performed to compare the safety, efficacy, and pharmacoeconomic of bivalirudin versus heparin in high-risk patients for percutaneous coronary interventions (PCI). Earlier meta-analysis comparing bivalirudin and heparin during PCI demonstrated that bivalirudin caused less bleeding with more stent thrombosis. However, little data were available on the safety of bivalirudin versus heparin in high-risk patients for PCI. Thus, we performed a meta-analysis to evaluate the efficacy and safety in the "high-risk" patients. A systematic search of electronic databases was conducted up to July 30, 2020. The Cochrane Risk of Bias assessment tool was used to assess the quality of included studies. The primary outcomes were all-cause death and major adverse cardiac events (MACE); secondary outcomes were major and minor bleeding, followed by a cost-minimization analysis comparing bivalirudin and heparin using a local drug and medical costs reported in China. Subgroup analysis was based on the type of disease of the high-risk population. Finally, a total of 10 randomized controlled trials involved 42,699 patients were collected. The Cochrane Risk of Bias Tool was employed to appraise the research quality. No significant difference was noted between bivalirudin and heparin regarding all-cause death and MACE. However, subgroup analysis showed that bivalirudin caused less major bleeding in female (OR:0.65, 95% CI:0.53-0.79), diabetes (OR:0.55, 95%CI:0.42-0.73), and CKD (OR:0.59, 95%CI:0.63-1.65). The scatterers of the included literature were approximately symmetrical, and no research was outside the funnel plot. Additionally, cost-minimization analysis showed that heparin was likely to represent a cost-effective option compared with bivalirudin in China, with potential savings of 2129.53 Chinese Yuan (CNY) per patient for one PCI. Overall, the meta-analysis showed that although bivalirudin appeared to have a lower risk of major bleeding rate, the overall effectiveness and safety between the two groups showed no significant difference in high-risk patients for PCI. But the results of the cost-minimization analysis showed that heparin could be a potential cost-saving drug than bivalirudin in patients for PCI in China.

Topics: Anticoagulants; Costs and Cost Analysis; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk; Treatment Outcome

Topics: Anticoagulants; Catheterization, Peripheral; Coronary Disease; Femoral Artery; Hemorrhage; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Punctures; Radial Artery; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

We sought to evaluate the efficacy and safety of bivalirudin versus heparin in patients with coronary artery disease undergoing transradial artery coronary intervention (TRI).. Bivalirudin and radial artery access are independently associated with improved cardiovascular outcomes. However, data supporting a strategy of combining both to achieve additive improvements in cardiovascular outcomes provide conflicting results.. A systematic search was performed to identify randomized controlled trials (RCTs) of bivalirudin, in which vascular access sites were reported. The primary outcome was net adverse clinical events (NACE) at 30 days. Secondary outcomes were long-term NACE, short-, and long-term major adverse cardiovascular events, all-cause mortality, myocardial infarction, unplanned revascularization, stent thrombosis, and major bleeding.. Among patients undergoing TRI, use of bivalirudin was associated with significantly reduced 30-day NACE compared with heparin. There was no significant difference in long term NACE, ischemic, or bleeding events compared with heparin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Catheterization, Peripheral; Coronary Artery Disease; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Punctures; Radial Artery; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The aim of this study was to explore the safety and efficacy of bivalirudin in elderly patients undergoing percutaneous coronary intervention (PCI).. An electronic search was conducted for randomized controlled trials with outcomes of interest in the elderly (≥ 65 years of age). Pooled risk ratios (RR) and 95% confidence interval (CI) using random effects Der Simonian-Laird models were calculated. Primary outcomes were net adverse clinical events (NACE) and major bleeding events at 30 days. Secondary outcomes were major adverse cardiac events (MACE) at 30 days. MACE, all-cause mortality, and NACE at 6-12 months were also examined.. Eleven trials that randomized a total of 15,895 elderly patients undergoing PCI to bivalirudin versus heparin were included. At 30 days, bivalirudin was associated with a reduced risk of NACE (0.86 [0.75-0.99], p = 0.04), mainly driven by reduction in major bleeding events (0.66 [0.54-0.80], p < 0.0001), as compared with heparin. On subgroup analyses based on the use of GPI in the heparin arm, benefit of major bleeding associated with bivalirudin appeared to be equally evident when GPI was used as a bailout (0.66 [0.46-0.94], p = 0.02) versus routine (0.67 [0.51-0.88], p = 0.004) adjunctive therapy with heparin. Subgroup analyses stratified by clinical presentation showed that benefit of bivalirudin in reducing NACE was even more obvious in the elderly group presenting with ST segment elevation myocardial infarction (STEMI) (0.76 [0.65-0.89], p = 0.0007), as compared with the overall (acute coronary syndrome or stable ischemic heart disease) group. No difference in MACE (0.94 [0.82-1.09], p = 0.42) was demonstrated between the two groups. Bivalirudin was associated with a similar risk of NACE (0.74 [0.39-1.42], p = 0.36) at 6 months and MACE (0.90 [0.68-1.19], p = 0.45) at 6-12 months, while a non-statistically significant trend toward lower all-cause mortality (0.70 [0.47-1.06], p = 0.09) at 1 year.. In elderly patients undergoing PCI, bivalirudin was associated with a lower risk of major bleeding events and the magnitude of benefit was not related to the use of GPI and irrespective of clinical presentation. Bivalirudin may reduce the NACE, particularly in elderly patients presenting with STEMI or in the setting of routine GPI use in the heparin arm, while no difference in MACE was demonstrated between the two groups.

Topics: Age Factors; Aged; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

Bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ), a direct thrombin inhibitor, has found increasing utilization as a heparin alternative in the pediatric population, most commonly for the treatment of thrombosis secondary to heparin-induced thrombocytopenia. Due to the relative rarity of heparin-induced thrombocytopenia as well as the lack of Food and Drug Administration-approved indications in this age group, much of what is known regarding the pharmacokinetics and pharmacodynamics of bivalirudin in this population has been extrapolated from adult data. This narrative review will present recommendations regarding the use of bivalirudin for procedural anticoagulation in the pediatric population based on the published literature.

Topics: Adolescent; Age Factors; Antithrombins; Blood Coagulation; Cardiac Catheterization; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child; Child, Preschool; Drug Administration Schedule; Drug Dosage Calculations; Hemorrhage; Hirudins; Humans; Infant; Infant, Newborn; Models, Biological; Peptide Fragments; Perioperative Care; Recombinant Proteins; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome

To evaluate the safety and efficacy of switching to bivalirudin during primary percutaneous coronary intervention (PCI) for patients who received preprocedure unfractionated heparin (UFH).. Current guidelines favor bivalirudin for primary PCI in patients at high risk of bleeding, particularly when femoral access is used. However, patients with ST-segment elevation myocardial infarction frequently receive UFH before arrival in the catheterization laboratory.. Scientific databases and websites were searched for randomized controlled trials. Patients were divided into those who received heparin with or without glycoprotein IIb/IIIa inhibitors (heparin group); those switched to bivalirudin during primary PCI from preprocedure UFH (switch group); and those who received bivalirudin without preprocedure UFH (Biv-alone group). Both traditional pairwise meta-analyses using moderator analyses and network meta-analyses using mixed-treatment comparison models were performed.. Data from five trials including13,547 patients were analyzed. In mixed-comparison models, switching to bivalirudin during primary PCI was associated with lower rates for all-cause mortality and major adverse cardiovascular events (MACEs) compared to the other strategies. Rates for all-cause mortality, MACEs, and net adverse clinical events (NACEs) were similar for the heparin and Biv-alone groups. Switching strategies was also associated with lower major bleeding rates compared to heparin alone. Similarly, in a standard pairwise model, both the switch and Biv-alone groups were associated with decreased bleeding risk compared to the heparin group. However, only the switch strategy was associated with decreased all-cause mortality (RR, 0.47; 95% CI, 0.30-0.75; P = 0.001), MACE (RR, 0.67; 95% CI, 0.49-0.91; P = 0.012), and NACE (RR, 0.61; 95% CI, 0.41-0.92; P = 0.019) compared with heparin alone.. During primary PCI, use of bivalirudin for those receiving preprocedure UFH was associated decreased rates for major bleeding, NACEs, MACEs, and all-cause mortality compared to heparin +/- GPI. This strategy was also associated with decreased rates for MACEs and all-cause mortality compared to bivalirudin alone without preprocedure UFH.

Topics: Anticoagulants; Antithrombins; Drug Substitution; Hemorrhage; Heparin; Hirudins; Humans; Network Meta-Analysis; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Bivalirudin may be an effective alternative anticoagulant to heparin for use in percutaneous peripheral interventions. We aimed to compare the safety and efficacy of bivalirudin versus heparin as the procedural anticoagulant agent in patients undergoing percutaneous peripheral intervention.. For this meta-analysis and systematic review, we conducted a search in PubMed, Medline, Embase, and Cochrane for all the clinical studies in which bivalirudin was compared to heparin as the procedural anticoagulant in percutaneous peripheral interventions. Outcomes studied included all-cause mortality, all-bleeding, major and minor bleeding, and access site complications.. Eleven studies were included in the analysis, totaling 20,137 patients. There was a significant difference favoring bivalirudin over heparin for all-cause mortality (risk ratio 0.58, 95% CI 0.39-0.87), all-bleeding (risk ratio 0.62, 95% CI 0.50-0.78), major bleeding (risk ratio 0.61, 95% CI 0.39-0.96), minor bleeding (risk ratio 0.66, 95% CI 0.47-0.92), and access site complications (risk ratio 0.66, 95% CI 0.51-0.84). There was no significant difference in peri-procedural need for blood transfusions (risk ratio 0.79, 95% CI 0.57-1.08), myocardial infarction (risk ratio 0.87, 95% CI 0.59-1.28), stroke (risk ratio 0.77, 95% CI 0.59-1.01), intracranial bleeding (risk ratio 0.77, 95% CI 0.29-2.02), or amputations (OR 0.75, 95% CI 0.53-1.05).. Our meta-analysis suggests that bivalirudin use for percutaneous peripheral interventions is associated with lower all-cause mortality, bleeding, and access site complications as compared to heparin. Further large randomized trials are needed to confirm the current results.

Topics: Aged; Anticoagulants; Antithrombins; Catheterization, Peripheral; Endovascular Procedures; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Peptide Fragments; Peripheral Arterial Disease; Recombinant Proteins; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome

In the review, we briefly describe antithrombotic drugs and the use evidence from evidence-based medicine to elucidate the optimal antithrombotic management for patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary stenting (PCI) at high risk of bleeding.. Mandatory use of intravenous anticoagulants and dual antiplatelet agents is the cornerstone strategy in acute and long-term antithrombotic management to optimize the clinical benefit of patients with STEMI undergoing PCI. Nevertheless, with the increasing occurrence of STEMI in old population with high risk of bleeding and renal insufficiency, as well as the specificity of high bleeding risk groups, the optimization of antithrombotic therapy still remains uncertain. Bivalirudin is the optimized intravenous anticoagulant agent for these patients based on the guideline recommendations and clinic data. Timely and potent ticagrelor and prasugrel with aspirin usage can increase the clinical benefit for the patients without increasing the clinical bleeding risk. At present, the multi-center, prospective clinical studies of EVOLVE short DAPT, MASTER DAPT, and POEM trials, targeting patients with high risk of bleeding, are in experimental stage. These clinical trials will provide more objective and optimal antithrombotic management strategy for the patients.

Topics: Anticoagulants; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recombinant Proteins; ST Elevation Myocardial Infarction; Stents; Ticagrelor

The direct thrombin inhibitor bivalirudin (BIV) was shown to be superior to unfractionated heparin (UFH) in percutaneous coronary interventions for reducing procedural blood loss. The aim of this study was to compare outcome profiles of BIV and UFH in peripheral endovascular procedures (PEPs) by synthesizing the currently available data.. Following the PRISMA statement, we conducted a comprehensive literature search using Medline, Cochrane CENTRAL, PubMed, EMBASE, CINAHL Google scholar, and clinicaltrials.gov. We recruited randomized, controlled trials and well-conducted observational studies that compared UFH and BIV in PEPs requiring anticoagulation, excluding endovascular cardiac procedures and coronary interventions. Random-effects meta-analyses were conducted to compare the outcome profiles of these two agents.. Thirteen articles containing 14 studies involving a total of 21,057 patients were enrolled. Of these, 2 were randomized controlled trials, 2 were prospective cohort studies, and 10 were retrospective studies. There were no significant differences between BIV and UFH in terms of procedural success rates, major and minor perioperative bleeding, transfusion, perioperative transient ischemic attack, or hemorrhagic strokes. However, compared with UFH, BIV had significantly lower odds ratios (OR) of perioperative mortality (OR, 0.58; 95% confidence interval [CI], 0.40-0.86), major adverse cardiovascular events (OR, 0.65; 95% CI, 0.51-0.83), net adverse clinical events (OR, 0.75; 95% CI, 0.63-0.88), perioperative myocardial infarction (OR, 0.73; 95% CI, 0.55-0.98), major vascular complications (OR, 0.59; 95% CI, 0.39-0.91), and minor vascular complications (OR, 0.58; 95% CI, 0.40-0.84).. Compared with UFH, PEPs using BIV had comparable procedural success rates and odds of perioperative transient ischemic attack and hemorrhagic stroke. However, procedures with BIV had a lower but nonsignificant odds of perioperative bleeding and transfusion. Depending on the procedures conducted, the patients who received BIV will have reduced or comparable odds of perioperative mortality, myocardial infarction, major adverse cardiovascular events, net adverse clinical events, and major and minor vascular complications. Therefore, BIV may be chosen solely as an alternative procedural anticoagulant to UFH for PEPs.

Topics: Anticoagulants; Antithrombins; Endovascular Procedures; Hemorrhage; Heparin; Hirudins; Humans; Ischemic Attack, Transient; Myocardial Infarction; Observational Studies as Topic; Patient Safety; Peptide Fragments; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Stroke; Treatment Outcome

Patients with chronic kidney disease (CKD) have elevated bleeding and ischemic outcomes. We aim to assess the short- and long-term efficacy and safety of bivalirudin compared to heparin plus glycoprotein IIb/IIIa inhibitors (GPIs) in coronary artery disease (CAD) patients with CKD.. Randomized trials were searched in PubMed, Cochrane, and Embase databases up to January 2017. Among the trials retrieved, efficacy endpoints were defined as mortality, myocardial infarction (MI), repeat revascularization, stent thrombosis, and major adverse cardiac events (MACEs). Safety endpoints were reported as non-coronary artery bypass grafting (CABG) related major bleeding and thrombolysis in myocardial infarction (TIMI) major bleeding. Risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome using a fixed effect model.. Five studies with a total of 3796 patients were included. In short-term follow up (30 days), bivalirudin significantly reduced non-CABG related major bleeding (p=0.0004) and TIMI major bleeding (p=0.007) compared to heparin plus GPIs. No significant differences were observed in rates of mortality, MI, repeat revascularization, stent thrombosis, and MACEs between the two groups in short- and long-term follow up (6 months to 3 years). In patients with ST elevated myocardial infarction (STEMI) with concurrent CKD, the decreased non-CABG related major bleeding (p=0.04) without increasing ischemic events was also observed after short-term follow up.. (1) Bivalirudin is safer than and as effective as heparin plus GPIs in CAD patients with CKD. (2) Impaired renal function does not affect the safety benefits of bivalirudin. (3) Similar efficacy profiles were identified between the two groups after both short- and long-term follow up in the CAD patients with CKD.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Kidney Function Tests; Male; Middle Aged; Myocardial Infarction; Patient Safety; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Insufficiency, Chronic; Thrombosis; Treatment Outcome

A number of studies suggest that bivalirudin (BIV) is associated with similar efficacy but reduced bleeding when compared with unfractionated heparin (UFH) in patients undergoing peripheral vascular interventions (PVI).. A comprehensive literature search was conducted with the electronic databases MEDLINE, EMBASE and CENTRAL. These were queried to identify studies comparing BIV with UFH in PVI. Study endpoints included total bleeding events, major and minor bleeding events and procedural success. Random-effects meta-analysis method was used to pool endpoint odds ratios (OR) for both UFH and BIV with 95% confidence intervals (CI).. A total of 12,335 patients (70.6 years; 59.7% male) were included from seven observational cohort studies (two prospective and five retrospective) comparing outcomes between BIV and UFH during PVI between January 2000 and May 2017. Compared with BIV, UFH was associated with significantly higher total bleeding, (OR 1.52 with 95% CI 1.11 to 2.09, p = 0.009), major bleeding (OR 1.38 with 95% CI 1.13 to 1.68, p = 0.002), and minor bleeding (OR 1.51 with 95% CI 1.09 to 2.08, p = 0.01). Procedural success rates were not different between the two groups (BIV vs HEP: OR 0.90 with 95% CI 0.49 to 1.64, p = 0.72) CONCLUSION: Compared with BIV, UFH was associated with more bleeding when used during PVI. There was no significant difference in procedural success between the two anticoagulation strategies.

Topics: Aged; Anticoagulants; Antithrombins; Endovascular Procedures; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Observational Studies as Topic; Peptide Fragments; Peripheral Vascular Diseases; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

This paper mainly focuses on the evidence above and gives brief discussion to the recent literature on anticoagulation in fibrinolytic therapy and advances in antiplatelet therapy.. To date, no robust evidence is available challenging unfractionated heparin as the primary choice for anticoagulation in patients presenting with ST-segment elevation myocardial infarction. Further research should include efforts to refine anticoagulation strategies on an individual patient level. For patients undergoing primary percutaneous coronary intervention, bivalirudin could be used as an alternative to unfractionated heparin, while enoxaparin or fondaparinux is an alternative agent for patients treated with fibrinolytic therapy.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Thrombosis; Treatment Outcome

We aimed to perform a gender-based meta-analysis of the outcome of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions (PCI).. Bivalirudin has been shown to decrease major bleeding when compared to heparin ± glycoprotein IIb/IIIa inhibitors (GPI) in patients undergoing PCI. It is unclear, however, if those differences in outcomes are the same for men and women.. We included randomized controlled trials (RCTs) that compared bivalirudin to heparin with or without GPI in patients undergoing PCI and reported outcome data that were stratified by gender. Random effect model was used to pool odds ratio (OR) and 95% confidence intervals (CI).. We included 9 trials with 33,224 patients. Bivalirudin decreased major bleeding when compared to heparin plus routine GPI in both men (OR: 0.51, P < 0.001) and women (OR: 0.55, P < 0.001). However, when GPI were used selectively with heparin, the bleeding lowering effect of bivalirudin was statistically significant in men (OR: 0.69, P = 0.02) but not in women (OR: 0.71, P = 0.21). When compared to heparin ± GPI, there was a nonstatistically significant trend toward lower all-cause mortality with bivalirudin in both men (OR: 0.76, P = 0.055) and women (OR: 0.79, P = 0.21). There were no significant differences in major adverse cardiovascular events between heparin and bivalirudin in both men and women.. Bivalirudin decreases major bleeding in both men and women when compared to heparin plus routine GPI. However, when compared to heparin alone, the bleeding lowering benefit of bivalirudin is less evident in women. © 2017 Wiley Periodicals, Inc.

Topics: Aged; Anticoagulants; Antithrombins; Coronary Artery Disease; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Sex Factors; Time Factors; Treatment Outcome

Transradial approach has significantly decreased the rate of access site bleeding in patients undergoing percutaneous coronary interventions (PCI), therefore potentially mitigating the benefits offered by bivalirudin in lowering major bleeding complications as compared to heparin. However, nonaccess site bleeding, that represent the majority of hemorrhagic complications, still carry negative prognostic consequences for these patients and no study has so far defined the exact impact of bivalirudin on nonaccess site bleeding, that was therefore the aim of present meta-analysis.. Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions were scanned comparing bivalirudin vs. heparin in patients undergoing PCI. Primary endpoint was the occurrence of nonaccess site bleeding within 30 days. Secondary endpoints were 30 days mortality and the occurrence of access-site bleeding.. The present meta-analysis shows that bivalirudin can provide a significant reduction of both access and nonaccess site bleeding in patients undergoing PCI. However, these hemorrhagic benefits did not impact on survival, and moreover, were significantly conditioned by the association of heparin with potent antithrombotic strategies, such as glycoprotein IIbIIIa inhibitors, rather than by heparin or bivalirudin alone. Therefore, we could not provide any clinical evidence for the routine use of bivalirudin as preferred anticoagulation strategy for PCI. © 2017 Wiley Periodicals, Inc.

Topics: Adolescent; Adult; Aged; Anticoagulants; Antithrombins; Chi-Square Distribution; Clinical Decision-Making; Coronary Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome; Young Adult

The first three hours after symptom onset hold the maximum potential for myocardial reperfusion and salvage in ST-elevation myocardial infarction (STEMI) patients. During this period timely primary percutaneous coronary intervention (PPCI) or, when PPCI is not promptly feasible, pre-hospital administration of fibrinolyis or a glycoprotein IIb/IIIa-inhibitor (GPI) have been shown to restore coronary patency and reperfusion and even result in myocardial infarction (MI) abortion. On the other hand, oral antiplatelet therapy may not yet guarantee sufficient platelet inhibition. Patients presenting after this golden time have less, if any, benefit from an aggressive antithrombotic treatment prior to PPCI. Antithrombotic treatment during primary angioplasty should be tailored on the basis of the coronary thrombotic burden, vascular approach and the patient's risk of bleeding complications. A GPI-based approach may be favourable in patients presenting early with large MI and high thrombus burden, whereas a bivalirudin-based approach without GPI may be preferred in patients with higher bleeding risk. There are no data to support the use of GPI in bailout conditions. The powerful oral P2Y

Topics: Angioplasty; Antithrombins; Emergency Medical Services; Hemorrhage; Hirudins; Humans; Meta-Analysis as Topic; Peptide Fragments; Recombinant Proteins; ST Elevation Myocardial Infarction

To compare the efficacies of various post-percutaneous coronary intervenetion (PCI) bivalirudin doses on net adverse clinical events (NACEs) and mortality.. In primary PCI, lower risk of bleeding with bivalirudin (vs. unfractionated heparin [UFH]) is counterbalanced by an increased risk of acute stent thrombosis (ST). Several randomized clinical trials (RCTs) and a recent meta-analysis suggest that acute ST risk may be eliminated without compromising the bleeding benefit, but only if the full dose, not a low dose, of bivalirudin is continued post-PCI. However, it is not known whether this improved risk leads to lower rates of NACEs and mortality.. Scientific databases and Web sites were searched for RCTs. Trials were included if study patients were undergoing primary PCI for acute ST-segment elevation myocardial infarction and were randomly assigned to bivalirudin or UFH treatment. The bivalirudin arm was divided based on post-PCI bivalirudin dosage: The Biv-Full group received 1.75 mg/kg/h, the Biv-Low group, 0.25 mg/kg/h, and the Biv-No group, none.. Six RCTs involving 16,842 patients were found. In pairwise meta-analysis, bivalirudin improved 30-day all-cause mortality by 35% and cardiac mortality by 32%, but did not yield a NACE rate better than that achieved with UFH. Subgroup analysis showed the Biv-Full group had a 46% lower NACE rate and 47% lower all-cause mortality than UFH. These effects were not seen in the other two groups. Network meta-analysis yielded similar results. At treatment ranking, the Biv-Full group yielded the best treatment efficacy.. In primary PCI, full-dose bivalirudin infusion for 3-4 hr after PCI appeared to improve NACE rates compared to UFH. It also seemed to be the most effective strategy for improving cardiac mortality and all-cause mortality. © 2016 Wiley Periodicals, Inc.

Topics: Anticoagulants; Antithrombins; Coronary Thrombosis; Hemorrhage; Heparin; Hirudins; Humans; Infusions, Intravenous; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; ST Elevation Myocardial Infarction; Stents; Time Factors; Treatment Outcome

To evaluate the impact of bivalirudin versus heparin on efficacy and safety outcomes of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (bailout vs. routine) of glycoprotein IIb/IIIa inhibitors (GPI).. Five randomized controlled trials encompassing 10,350 patients were included. Primary efficacy and safety endpoints were all-cause death and major bleeding, respectively. All-cause death at 30 days did not significantly differ with bivalirudin compared to heparin (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.74-1.28; P=0.84). Major bleeding was significantly reduced by bivalirudin compared to heparin (OR 0.58, 95% CI 0.40-0.85; P=0.005). Bivalirudin use was associated with non-significantly different rates of 30-day definite stent thrombosis (ST) (OR 1.71, 95% CI 0.84-3.49; P=0.14), albeit with higher rates of acute ST (OR 3.55, 95% CI 1.67-7.56; P=0.001) and non-significantly different rates of subacute ST (OR 0.86, 95% CI 0.46-1.61; P=0.64). There were non-significant differences in the 30-day rates of reinfarction (OR 1.47, 95% CI 0.94-2.30; P=0.10) and cardiovascular death (OR 0.76, 95% CI 0.56-1.02; P=0.07). There were no significant interactions between bailout versus routine GPI use in the heparin arm for any of the safety or efficacy outcomes (all Pinteraction>0.10).. Bivalirudin compared with heparin was associated with comparable 30-day rates of mortality with reduced major bleeding, at the price of an increased risk of acute ST, with non-significant differences in the overall 30-day rates of ST and reinfarction. Intended use of GPI in the heparin arm did not significantly modify the treatment effects of bivalirudin. Given the important differences between trials, as well as evolution in technique and adjunct pharmacotherapy, further randomized trials are warranted to discriminate whether there are substantial safety and efficacy differences between these agents during primary PCI in STEMI.

Topics: Aged; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; ST Elevation Myocardial Infarction

To evaluate direct comparisons of bivalirudin versus unfractionated heparin (UFH) as anticoagulants during ST-segment elevation myocardial infarction (STEMI) in patients undergoing primary percutaneous coronary intervention (PPCI).. Relevant information was identified through a search of MEDLINE (1966-September 2015), International Pharmaceutical Abstracts (1960-September 2015), and Cochrane Databases (publications archived until September 2015) using the terms bivalirudin, unfractionated heparin, ST-segment elevation myocardial infarction, and primary percutaneous coronary intervention.. English-language randomized controlled trials and meta-analyses were eligible for inclusion for data review of STEMI where PPCI was performed.. Either bivalirudin or UFH is recommended in the setting of STEMI where PPCI is to be performed. Bivalirudin is touted for its predictable pharmacokinetics, effects on thrombin-mediated platelet inhibition, and favorable outcomes with regard to adverse bleeding profiles, whereas UFH, the gold standard anticoagulant during PPCI, remains a viable treatment strategy. Only recently have direct comparisons of UFH and bivalirudin during PPCI become available. The evidence available is complicated by variances in use of glycoprotein IIb/IIIa inhibitors (GPIs), P2Y12 inhibitors, access sites, and anticoagulant dosing strategies. We provide a review of contemporary trials and advancements in this area.. When compared to UFH with limited use of GPI, available evidence demonstrates that bivalirudin reduces bleeding at the expense of increasing risk for acute stent thrombosis. Further randomized studies are needed to determine the potential benefits of a post-PCI infusion of bivalirudin to reduce the risk for acute stent thrombosis, long-term follow-up beyond 30 days, and mortality.

Topics: Anticoagulants; Antithrombins; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins

The aim of this study was to evaluate the efficacy of various doses of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion to prevent acute stent thrombosis (AST).. In several recent randomized controlled trials, bivalirudin infusion was continued post-PCI as either a full PCI dose (Biv-Full) or a reduced dose (Biv-Low) to reduce the risk for AST. The results of these trials varied, so the authors performed a meta-analysis of RCTs to determine whether the risk for AST is dose dependent.. Scientific databases and Web sites were searched for RCTs. A traditional meta-analysis was performed using moderator analyses and network meta-analysis using mixed-treatment comparison models to compare the efficacy of various bivalirudin doses in reducing AST.. Data from 5 trials including 16,294 patients were analyzed. Compared with heparin, bivalirudin increased AST risk 2-fold, but this was ameliorated by continuing Biv-Full (risk ratio: 0.90, 95% confidence interval: 0.32 to 2.54; p = 0.852). This effect was not seen with Biv-Low. Similarly, in mixed-treatment models, no difference in AST rate was found between heparin and Biv-Full (odds ratio: 0.97; 95% confidence interval: 0.36 to 2.21). After 30 days, bivalirudin decreased the risk for major bleeding by 47% compared with heparin; this benefit persisted even with continued Biv-Full post-PCI (risk ratio: 0.29; 95% confidence interval: 0.16 to 0.53; p < 0.001).. Although bivalirudin is associated with a greater risk for AST than heparin post-primary PCI, this limitation may be mitigated by continuing Biv-Full (not Biv-Low) 3 to 4 h post-operatively. The decrease in bleeding risk with bivalirudin compared with heparin is not compromised by this strategy.

Topics: Acute Disease; Anticoagulants; Antithrombins; Coronary Thrombosis; Dose-Response Relationship, Drug; Evidence-Based Medicine; Hemorrhage; Heparin; Hirudins; Humans; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; ST Elevation Myocardial Infarction; Stents; Time Factors; Treatment Outcome

Recent randomized control trials (RCTs) showed conflicting efficacy and safety between bivalirudin and heparin during percutaneous coronary intervention (PCI). We aimed to perform an updated meta-analysis, including real-world and trial data to examine the factors affecting their risk-benefit ratio.. We searched Medline, the Cochrane library, and meeting abstracts for studies comparing bivalirudin versus heparin during PCI. Random-effect meta-analyses for MACE (major adverse cardiovascular events), stent thrombosis (ST) and major bleeding were performed. p-Value <0.05 was considered statistically significant.. Meta-analysis of 20 RCTs and 31 observation studies (n=165,835) showed that bivalirudin and heparin were similar in the risk of MACE in RCTs (OR 1.05, 95% CI 0.97-1.13) and observational studies (OR 0.94, 95% 0.81-1.10). Major bleeding was lower with bivalirudin in both RCTs (OR 0.60, 95% CI 0.51-0.70) and observational studies (OR 0.56, 95% CI 0.47-0.68). However, in the metaregression analysis, every 10% increase of transradial access decreased the bleeding benefit of bivalirudin by 4.9% (p=0.046, adjusted for GPI and heparin loading dose). ST with bivalirudin was higher with ST-segment elevation myocardial infarction (STEMI) in RCTs (OR 1.51, 95% CI 1.15-1.99) but not in observational studies (p=0.65).. In this large meta-analysis, bivalirudin is associated with a lower risk of bleeding compared to heparin in both RCTs and observational studies, however, transradial PCI mitigated most of this bleeding benefit. Heparin should be the preferred agent in transradial PCI given its lower cost and comparable outcomes.

Topics: Anticoagulants; Comparative Effectiveness Research; Coronary Occlusion; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk Assessment

The optimal antithrombotic therapy in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) remains a matter of debate. This updated meta-analysis investigated the impact of (1) bivalirudin (with and without prolonged infusion) and (2) prolonged PCI-dose (1.75 mg/hg per hour) bivalirudin infusion compared with conventional antithrombotic therapy on clinical outcomes in patients undergoing primary PCI.. Eligible randomized trials were searched through MEDLINE, EMBASE, Cochrane database, and proceedings of major congresses. Prespecified outcomes were major bleeding (thrombolysis in myocardial infarction major and Bleeding Academic Research Consortium 3-5), acute stent thrombosis, as well as all-cause and cardiac mortality at 30 days. Six randomized trials (n=17 294) were included. Bivalirudin compared with heparin (+/- glycoprotein-IIb/IIIa inhibitor) was associated with reduction in major bleeding (odds ratio [OR]: 0.65, 95% CI: 0.48-0.88, P=0.006, derived from all 6 trials), increase in acute stent thrombosis (OR: 2.75, 95% CI: 1.46-5.18, P=0.002, 5 trials), and lower rate of all-cause mortality (OR: 0.81, 95% CI: 0.67-0.98, P=0.03, 6 trials) as well as cardiac mortality (OR: 0.69, 95% CI: 0.55-0.87, P=0.001, 5 trials). The incidence of acute stent thrombosis did not differ between the prolonged PCI-dose bivalirudin and comparator group (OR: 0.81, 95% CI: 0.27-2.46, P=0.71, 3 trials), whereas the risk of bleeding was reduced despite treatment with high-dose bivalirudin infusion (OR: 0.28, 95% CI: 0.13-0.60, P=0.001, 3 trials).. Bivalirudin (with and without prolonged infusion) compared with conventional antithrombotic therapy in ST-segment-elevation myocardial infarction patients undergoing primary PCI reduces major bleeding and death, but increases the rate of acute stent thrombosis. However, prolonging the bivalirudin infusion at PCI-dose (1.75 mg/kg per hour) for 3 hours eliminates the excess risk of acute stent thrombosis, while maintaining the bleeding benefits.

Topics: Antithrombins; Hemorrhage; Hirudins; Humans; Infusions, Intravenous; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; ST Elevation Myocardial Infarction; Stents; Thrombosis

The aim of this meta-analysis was to study the relation between access site and bivalirudin use on outcomes in patients with acute coronary syndrome (ACS).. Bivalirudin and radial access use are 2 strategies that are increasingly used to lower major bleeding in patients with ACS undergoing invasive approaches. The interaction between these 2 strategies and the benefit of using them in combination are unclear.. This analysis included randomized controlled trials that compared bivalirudin to heparin with or without glycoprotein IIb/IIIa inhibitors in patients with ACS and reported outcomes stratified by arterial access site. Meta-analyses of outcome data were performed on the basis of access site and anticoagulation regimen. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from event rates using random-effects models.. Eight trials with a total of 27,491 patients were included. Bivalirudin reduced major bleeding risk in patients with femoral access (OR: 0.51; 95% CI: 0.46 to 0.6; p < 0.001) but not in patients with radial access (OR: 0.75; 95% CI: 0.45 to 1.26; p = 0.28). Moreover, radial access reduced major bleeding risk in patients treated with heparin (OR: 0.57; 95% CI: 0.43 to 0.77; p < 0.001) but not in patients treated with bivalirudin (OR: 0.96; 95% CI: 0.65 to 1.41; p = 0.83). There were no differences in major adverse cardiovascular events or all-cause mortality between bivalirudin and heparin, regardless of access site.. Bivalirudin reduces bleeding risk only with femoral access, and radial access reduces bleeding risk only with heparin anticoagulation. Therefore, there is no additional benefit to the combined use of bivalirudin and radial access strategies in patients with ACS.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Catheterization, Peripheral; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Radial Artery; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Treatment Outcome

Numerous GPIs are available for PCI. Although they were tested in randomized controlled trials, a comparison between the different GPI strategies is lacking. Thus, we performed a Bayesian network meta-analysis to compare different glycoprotein IIb/IIIa inhibitor (GPI) strategies with heparin and bivalirudin for percutaneous coronary intervention (PCI).. MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched by two independent reviewers for randomized controlled trials comparing high-dose bolus tirofiban, abciximab, eptifibatide, heparin with provisional glycoprotein IIb/IIIa inhibitors, and bivalirudin with provisional GPI that reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare between different anticoagulation strategies for all-cause mortality, myocardial infarction, major adverse cardiovascular events, major bleeding, minor bleeding, need for transfusion, and thrombocytopenia.. A total of 41 randomized controlled trials with 38,645 patients were included in the analysis, among which 2654 were randomized to high-dose bolus tirofiban, 6752 to abciximab, 1669 to eptifibatide, 16,500 to heparin, and 11,070 to bivalirudin. Mean age was 64±11years, 75% were male, 91% were treated with stenting, 71% with clopidogrel, and 74% for acute coronary syndrome. High-dose bolus tirofiban was associated with a significant reduction in all-cause mortality compared with heparin (OR 0.57 [credible intervals 0.37, 0.9]) and eptifibatide (OR 0.44 [credible intervals 0.19, 1.0]). GPI regimens had less myocardial infarction and major adverse cardiovascular events but greater bleeding compared with heparin and bivalirudin. There was no difference among the GPI therapies for other outcomes, including myocardial infarction, major adverse cardiovascular events, and major bleeding.. Our network meta-analysis of 38,645 patients demonstrated that GPI regimens were associated with a reduction in recurrent myocardial infarction or major adverse cardiovascular events for PCI, while bivalirudin was associated with the lowest risk of bleeding.

Topics: Aged; Anticoagulants; Bayes Theorem; Blood Transfusion; Coronary Thrombosis; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Risk Factors; Thrombocytopenia; Time Factors; Treatment Outcome

Current recommendations on the use of bivalirudin in patients treated with percutaneous coronary intervention (PCI) are mostly based on trials comparing bivalirudin versus heparin plus planned glycoprotein IIb/IIIa inhibitor (GPI). Whether bivalirudin is also superior to heparin alone is still not well established. This meta-analysis investigates the efficacy and safety of bivalirudin versus heparin in patients treated with PCI without planned use of GPI.. Scientific databases and websites were searched for randomised controlled trials. The primary efficacy and safety outcomes were the 30-day incidence of death and major bleeding, respectively. The secondary outcomes were the 30-day incidence of myocardial infarction (MI), definite stent thrombosis (ST), urgent target vessel revascularisation (TVR), and overall death at the longest available follow-up. Odds ratio (OR) and 95% confidence interval (95% CI) served as summary statistics. Ten trials were identified including a total of 18,065 PCI patients randomised to bivalirudin (n=9,033) versus heparin (n=9,032). At 30 days, bivalirudin versus heparin showed a comparable risk of death (1.09 [0.83-1.41], p=0.54), and MI (1.10 [0.83-1.46], p=0.50) with a trend towards a higher risk of urgent TVR (1.37 [0.96-1.96], p=0.08). The risk of major bleeding was lower with bivalirudin (0.57 [0.40-0.80], p=0.001) and the bleeding reduction was more evident when high doses of heparin were used as comparator (p for interaction <0.001). The risk of definite ST (2.09 [1.26-3.47], p=0.005) and, in particular, the risk of acute ST (3.48 [1.66-7.28], p<0.001) was increased by bivalirudin.. Patients undergoing PCI randomised to therapy with either bivalirudin or heparin display a similar mortality. Bivalirudin as compared to heparin appears to reduce the risk of major bleeding at the expense of a higher risk of acute ST.

Topics: Aged; Anticoagulants; Antithrombins; Databases, Factual; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins

Bivalirudin is a valuable anticoagulant option in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention. Advantages over heparin as a parenteral anticoagulant include more predictable pharmacokinetics and pharmacodynamics, shorter half-life, no need for cofactors, some degree of antiplatelet effect, and the ability to inhibit clot-bound thrombin. Clinical evidence supporting the use of bivalirudin over heparin in current ACS guidelines, however, derives mostly from early randomised trials that may no longer reflect current management patterns, now including the use of oral antiplatelet agents more potent than clopidogrel (i.e. prasugrel or ticagrelor) and a broader implementation of strategies to reduce bleeding (i.e. radial access for percutaneous coronary intervention, and use of glycoprotein IIb/IIIa inhibitors only in bailout situations). Defining the fine balance between bivalirudin efficacy and safety over heparins in the context of other antithrombotic treatments remains a challenge in clinical practice, particularly in a fast-evolving scenario, such as ACS, where numerous new trials have been presented in very recent times. Here we provide an up-to-date overview of the evidence on the use of bivalirudin in ACS, with focus on new data, open issues, and future directions.

Topics: Acute Coronary Syndrome; Anticoagulants; Cost-Benefit Analysis; Drug Costs; Hemorrhage; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

The use of extracorporeal membrane oxygenation (ECMO) support for cardiac and respiratory failure has increased in recent years. Improvements in ECMO oxygenator and pump technologies have aided this increase in utilization. Additionally, reports of successful outcomes in supporting patients with respiratory failure during the 2009 H1N1 pandemic and reports of ECMO during cardiopulmonary resuscitation have led to increased uptake of ECMO. Patients requiring ECMO are a heterogenous group of critically ill patients with cardiac and respiratory failure. Bleeding and thrombotic complications remain a leading cause of morbidity and mortality in patients on ECMO. In this review, we describe the mechanisms and management of hemostatic, thrombotic and hemolytic complications during ECMO support.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Cardiac Output, Low; Cardiac Tamponade; Extracorporeal Membrane Oxygenation; Hemolysis; Hemorheology; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Respiratory Insufficiency; Thrombosis; von Willebrand Diseases

The aim of this meta-analysis was to compare the 30-day safety and efficacy of bivalirudin with those of heparin with or without routine administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute coronary syndrome (ACS).. Bivalirudin has been a mainstay of anticoagulation in patients with ACS compared with heparin. The extent to which trial results have been affected by the coadministration of heparin with a GPI, however, remains unclear.. A total of 13 randomized, controlled trials involving 24,605 patients were included.. There was no significant difference in 30-day mortality or myocardial infarction rate with bivalirudin compared with heparin with or without routine GPI administration. A reduction of 30-day major bleeding was observed with bivalirudin compared with heparin that was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally administered GPI (OR: 0.66, 95% CI: 0.33 to 1.32; p = 0.24). The occurrence of stent thrombosis (ST) at 30 days was significantly increased with bivalirudin compared with heparin plus routinely administered GPI (OR: 1.67, 95% CI: 1.13 to 2.45, p = 0.02), but not compared with heparin plus provisionally administered GPI (OR: 2.08, 95% CI: 0.35 to 12.32, p = 0.42). The rate of acute ST (≤ 24 h), however, was almost 4.5-fold higher with bivalirudin compared with heparin with or without GPI, whereas the rate of subacute ST (24 h to 30 days) did not differ significantly.. Overall, bivalirudin in ACS patients is associated with a significant reduction of major bleeding compared with heparin plus routinely administered GPI, but with a marked increase in ST rates compared with heparin with or without GPI.

Topics: Acute Coronary Syndrome; Anticoagulants; Blood Platelets; Chi-Square Distribution; Coronary Thrombosis; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Odds Ratio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

Our aim was to compare the efficacy and safety of bivalirudin (Biv) versus heparin (Hep) with or without similar usage rate of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI). The PubMed and EMbase were searched. Randomized trials comparing Biv versus Hep were eligible for inclusion. With imbalanced GPI use, Biv had significantly lower major bleeding (pooled risk ratio [RR], 0.67; 95% confidence interval [CI], 0.54-0.83) without difference in mortality (pooled RR, 0.95; 95% CI, 0.80-1.14). With comparable GPI use, no significant difference was observed in major bleeding (pooled RR, 0.95; 95% CI, 0.82-1.10) and mortality (pooled RR, 1.13; 95% CI, 0.85-1.50). With no GPI use, Biv was associated with numerically higher mortality (pooled RR, 1.17; 95% CI, 0.83-1.65) without significant difference in major bleeding (pooled RR, 0.81; 95% CI, 0.64-1.02). In conclusion, when comparing different anticoagulants during PCI, the effect of GPIs should not be underestimated. Heparin as such was found noninferior to Biv.

Topics: Anticoagulants; Antithrombins; Chi-Square Distribution; Coronary Thrombosis; Hemorrhage; Heparin; Hirudins; Humans; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

Although bivalirudin has been shown to reduce bleeding events in patients undergoing percutaneous coronary intervention, residual concerns remain about a possible higher risk of early (within 30 days) stent thrombosis (ST). Therefore, we performed a meta-analysis of randomised trials reporting ST events with bivalirudin compared to other antithrombotic therapies (heparins ± glycoprotein IIb/IIIa inhibitors). A systematic literature search of electronic resources was performed through May, 2014. The primary endpoint was definite early ST, according to Academic Research Consortium criteria. Secondary endpoints included: all-cause death, myocardial infarction and major bleeding. A total of 11 trials, including 16,415 patients, were accrued. Compared to other regimens, bivalirudin significantly increased the risk of early ST (odds ratio [OR]=1.80; 95 % confidence interval [CI], 1.28-2.52; p=0.0007) and reduced the risk of major bleeding (OR [95 %CI]=0.64 [0.51-0.82], p=0.0003), with a comparable risk of mortality or myocardial infarction. The higher risk of early ST was mainly attributable to acute (OR [95 % CI] =4.33 [2.33-8.05], p < 0.001) than subacute (OR [95 % CI] =0.89 [0.53-1.50], p =0.67) ST events (p for interaction < 0.001). Non-fatal myocardial infarction was the most common presentation (83 %) of early ST events, while death occurred infrequently (about 5 %). In conclusion, in patients undergoing PCI, bivalirudin compared to heparins is associated with a higher risk of early ST, which is mainly related to more frequent acute events. Further studies are required to evaluate alternative strategies to mitigate this risk, without hampering the benefits derived from the reduction in bleeding events with bivalirudin.

Topics: Acute Disease; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Multicenter Studies as Topic; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk; Stents; Thrombosis; Treatment Outcome

Bivalirudin has gained ground against unfractionated heparin (UFH) in percutaneous coronary interventions (PCI), due to a reported better safety profile. However, whether bivalirudin may provide also advantages in clinical outcome beyond the known benefits in major bleedings, is still a debated matter and was, therefore, the aim of present meta-analysis of randomized trials, evaluating efficacy and safety of bivalirudin as compared with UFH in PCI.. Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions were scanned. Primary endpoint was overall mortality. Secondary endpoints were: 1) mortality within 30-days; 2) overall and within 30-days non fatal myocardial infarction; 3) overall and within 30-days stent thrombosis. Safety endpoints were major bleedings (per protocol definition or TIMI classification). A prespecified analysis was conducted according to clinical presentation (Elective, ACS, STEMI).. A total of 22 randomized clinical were finally included, involving 40156 patients randomized to bivalirudin (52.9%) or to UFH (47.1%). Death occurred in 1100 (2.8%) of patients, with no difference between bivalirudin and UFH (2.7% vs 2.8% OR[95%C]=0.94[0.83,-.06], p=0.32, phet=0.48). The results did not change according to clinical presentation. By meta-regression analysis, the effects on mortality were not related to patients risk profile (r=-0.38(-0.89-0.14), p=0.15) or the reduction in bleeding complications (r=-0.008(-0.86-0.85), p=0.98). A significant increase in short-term stent thrombosis was observed with bivalirudin (OR[95%CI]=1.42 [1.10-1.83], p=0.006). However, Bivalirudin significantly reduced bleedings according to both study protocol definition (OR[95%CI]=0.62[0.56-0.69],p<0.00001; phet=0.0003) or TIMI major criteria (OR[95%CI]=0.65[0.53-0.79],p<0.0001, phet=0.95).. In present meta-analysis, among patients undergoing PCI, bivalirudin, as compared with UFH, is associated with a significant reduction in major bleeding complications that, however, does not translate into mortality benefits. Furthermore, bivalirudin is associated with higher rate of 30-days stent thrombosis and recurrent MI among STEMI patients.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombosis

Diabetes mellitus (DM) is a pro-thrombotic state with enhanced thrombin generation and platelet reactivity. For most patients undergoing percutaneous coronary intervention (PCI), bivalirudin demonstrates efficacy comparable with that of heparin and glycoprotein IIb/IIIa inhibitors (GPIs). Yet, because of their pro-thrombotic condition, we hypothesized that patients with DM may benefit from more aggressive dual antithrombin and antiplatelet therapy. The aim of this paper was to provide a systematic review comparing outcomes of PCI with bivalirudin versus heparin plus GPI in patients with DM using meta-analytical techniques. Eligible studies needed to have reported a subgroup analysis of outcomes among diabetic patients. Six trials comprising 5924 diabetic patients were eligible. At 30 days, bivalirudin was associated with a reduction in net adverse cardiac events [relative risk (RR) 0.81, 95 % confidence interval (CI) 0.70-0.93, p = 0.002] and major bleeds (RR 0.68, 95 % CI 0.49-0.95; p = 0.02), with no difference in composite ischemia (RR 0.92, 95 % CI 0.74-1.14; p = 0.43) or mortality (RR 0.71, 95 % CI 0.45-1.13; p = 0.15). At 1 year, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.73, 95 % CI 0.54-1.00, p = 0.05) despite similar composite ischemia (RR 1.02, 95 % CI 0.56-1.21, p = 0.811). In conclusion, thrombin inhibition with bivalirudin alone was associated with reduced 30-day major bleeding and 1-year all-cause mortality compared with heparin plus GPI in diabetic patients undergoing PCI.

Topics: Antithrombins; Blood Coagulation; Coronary Restenosis; Diabetes Complications; Drug Therapy, Combination; Hemorrhage; Heparin; Hirudins; Humans; Outcome Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins

For decades, unfractionated heparin (UFH) has been widely used in catheterization laboratories for anticoagulation for percutaneous coronary intervention (PCI). The direct thrombin inhibitors, bivalirudin, has emerged as an alternative to UFH for PCI procedures, due to its lower bleeding risk. More recently, randomized trials and meta-analyses questioned the efficacy of bivalirudin, and demonstrated that bivalirudin might be associated with a higher incidence of ischemic events and in particular stent thrombosis. In this review, we discuss the pharmacology of bivalirudin along with the clinical evidence comparing bivalirudin versus UFH in patients undergoing PCI for various indications.

Topics: Acute Coronary Syndrome; Animals; Anticoagulants; Coronary Thrombosis; Cost-Benefit Analysis; Drug Costs; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

Percutaneous coronary intervention can lead to vascular access complications that prolong patient hospital stay and costs as well as increase patient morbidity and mortality. Given its ease of use and familiarity, transfemoral access is still the preferred method of approach by many operators. The transfemoral approach is used when large bore access is required or if transradial access is not feasible due to variations in the anatomy of the upper extremity artery. The use of fluoroscopy, ultrasonography, and femoral angiography can help the operator obtain proper arteriotomy of the common femoral artery. Measures to decrease vascular access complications include proper technique, optimal pharmacotherapy, and avoiding the use of arterial sheaths >6 Fr. Optimal pharmacotherapy includes the use of bivalirudin and weight-based unfractionated heparin to avoid supratherapeutic activated clotting times, and to avoid glycoprotein IIb/IIIa inhibitors. When used appropriately, vascular closure devices can decrease the risk of bleeding complications. Randomized trials are needed to confirm these recommendations.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Vessels; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Radiography; Recombinant Proteins; Vascular Closure Devices

Both ST-segment elevation myocardial infarction and percutaneous coronary intervention (PCI) are associated with a highly prothrombotic state, and thrombin plays a critical role during occlusive clot generation and subsequent occurrence of an ischemic event. Therefore, a strategy of anticoagulation plus dual antiplatelet therapy has been regarded as de facto standard therapy during primary PCI (pPCI). Recently, there has been great controversy surrounding the role of bivalirudin versus unfractionated heparin in pPCI. Earlier, the results of the HORIZONS-AMI trial, particularly those regarding the long-lasting mortality benefit, provided a strong rationale for recommending bivalirudin therapy in pPCI. However, the mortality benefit of bivalirudin observed in HORIZONS-AMI has not been repeated in more contemporary studies or demonstrated in recent meta-analyses. The current report will provide a concise review of the controversy surrounding the optimal anticoagulant therapy for pPCI. Recent evidence suggests that unfractionated heparin deserves strong reconsideration despite the reports of pharmacologic weaknesses, particularly when used with a strategy of selective glycoprotein IIb/IIIa therapy, and it appears that a strategy of bivalirudin therapy in pPCI should be reserved for patients at high bleeding risk.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

Percutaneous coronary intervention with bivalirudin plus bail-out glycoprotein IIb/IIIa inhibitors has been shown to be as effective as unfractionated heparin plus routine glycoprotein IIb/IIIa inhibitors in preventing cardiac ischemic events, but with a lower bleeding risk. It is unknown whether bivalirudin would have the same beneficial effects if compared with heparin when the use of glycoprotein IIb/IIIa inhibitors was similar between treatment arms. We searched the MEDLINE, Web of Science, and Cochrane databases from inception until March 2015 for randomized trials that compared bivalirudin to heparin in patients undergoing percutaneous coronary intervention. We required that the intended use of glycoprotein IIb/IIIa inhibitors was similar between the study groups. Summary estimates were principally constructed by the Peto method. Fifteen trials met our inclusion criteria, which yielded 25,824 patients. Bivalirudin versus heparin was associated with an increased hazard of stent thrombosis (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.15-1.92, P = .002, I2 = 16.9%), with a similar hazard of myocardial infarction (OR 1.09, 95% CI 0.98-1.22, P = .11, I2 = 35.8%), all-cause mortality (OR 0.88, 95% CI 0.72-1.08, P = .21, I2 = 31.5%) and major adverse cardiac events (OR 1.04, 95% CI 0.94-1.14, P = .46, I2 = 53.9%). Bivalirudin was associated with a reduced hazard of major bleeding (OR 0.80, 95% CI 0.70-0.92, P = .001, I2 = 63.5%). The dose of heparin in the control arm modified this association; when the dose of unfractionated heparin in the control arm was ≥ 100 units/kg, bivalirudin was associated with a reduction in major bleeding (OR 0.55, 95% CI 0.45-0.68, P < .0001), but when the dose of unfractionated heparin was ≤ 75 units/kg, bivalirudin was not associated with reduction in bleeding (OR 1.09, 95% CI 0.91-1.31, P = .36). Among patients undergoing PCI, bivalirudin was associated with an increased hazard of stent thrombosis. Bivalirudin may be associated with a reduced hazard of major bleeding; however, this benefit was no longer apparent when compared with a dose of unfractionated heparin ≤ 75 units/kg.

Topics: Acute Coronary Syndrome; Dose-Response Relationship, Drug; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Stents; Thrombosis; Treatment Outcome

Bivalirudin is commonly used for patients undergoing percutaneous coronary intervention (PCI), but there have been recent concerns that it may be associated with an increased risk of stent thrombosis and provide no benefit regarding major bleeding compared with active control.. We searched PubMed, clinicaltrials.gov, and conference proceedings for randomized controlled trials of bivalirudin versus active control in patients undergoing PCI. The main outcomes of interest were definite stent thrombosis, myocardial infarction, major bleeding, and mortality. We used random-effects modeling to pool the data. We included 25 trials involving 41,243 patients. Overall, use of bivalirudin compared with active control was associated with an increased risk of definite stent thrombosis (11 trials; 16,864 patients; RR, 1.73; 95% CI, 1.24-2.40; P<0.001; I(2)=0%), similar risk of acute myocardial infarction (22 trials; 40,578 patients; RR, 1.00; 95% CI, 0.87-1.16; P=0.96; I(2)=43%), decreased risk of major bleeding (25 trials; 41,243 patients; RR, 0.59; 95% CI, 0.49-0.72; P<0.001; I(2)=31%) and of cardiac death (6 trials; 6,956 patients; RR, 0.72; 95% CI, 0.53-0.99; P=0.05; I(2)=0%), but no change in all-cause mortality (24 trials; 41,058 patients; RR, 0.96; 95% CI, 0.81-1.15; P=0.69; I(2)=0%). Results were consistent across a wide set of subgroup and sensitivity analyses.. Compared with active control, bivalirudin is associated with increased risk of stent thrombosis but lower risk of major bleeding, with no discernible impact on all-cause mortality.

Topics: Antithrombins; Hemorrhage; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk; Stents; Thrombosis

Patients treated with bivalirudin in randomized clinical trials of percutaneous coronary intervention generally have less bleeding but more acute stent thrombosis (ST) than do patients treated with heparin, but differences have varied among trials.. We modeled the risk of major hemorrhage and ischemic outcomes 30 days after percutaneous coronary intervention by treatment assignment and the use of adjunctive therapies in 18 randomized clinical trials enrolling 41,871 patients. Overall bivalirudin caused less major bleeding (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53-0.76), more ST (OR, 1.58; 95% CI, 1.19-2.09), and no difference in mortality (OR, 0.93; 95% CI, 0.77-1.14) than heparin. A risk-benefit analysis identified 19 fewer bleeds and 5 more STs for every 1000 patients treated with bivalirudin in place of heparin. No significant bleeding advantage of bivalirudin over heparin could be identified in randomized clinical trials when transradial access (OR, 0.89; 95% CI, 0.57-1.41) and planned glycoprotein IIb/IIIa inhibitors were used with bivalirudin in the majority of patients (OR, 1.07; 95% CI, 0.87-1.31). The use of prasugrel or ticagrelor eliminated bleeding differences (OR, 0.80; 95% CI, 0.63-1.03) but did not reduce the risk of ST after bivalirudin (OR, 2.20; 95% CI, 1.48-3.27).. Substituting bivalirudin for heparin conferred a tradeoff between bleeding and ST. Transradial access, adjunctive glycoprotein IIb/IIIa inhibitors, and potent P2Y12 inhibitors attenuated the bleeding advantage of bivalirudin over heparin but had no apparent effect on early ST. New approaches to reduce bleeding and ischemic complications during percutaneous coronary intervention warrant further investigation.

Topics: Clinical Trials as Topic; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Stents; Thrombosis

Bleeding complications are among the most common complications of percutaneous coronary intervention (PCI) procedures. A multitude of studies carried out over the last decade have confirmed that bleeding complications after PCI have a negative impact on patients' outcome (dissatisfaction, morbidity, and mortality) and hospital indices (length of stay and costs). Apart from better recognition and classification of bleeding, recent research has helped to device several risk stratification tools that have markedly improved prediction of peri-PCI bleeding. Moreover, parallel with the recognition of the deleterious effects of peri-PCI bleeding, several strategies (pre-PCI risk stratification for bleeding, the use of bivalirudin as an antithrombotic/anticoagulant strategy, the radial artery route for vascular access and vascular closure devices) that aim to reduce peri-PCI bleeding were developed and used. Their application has markedly reduced the incidence of bleeding and improved the clinical outcome. In this review, we focus primarily on the bleeding complications occurring during PCI procedures. Specifically, we summarize recent research on the need for a consensus in bleeding definition, incidence of bleeding events, and their impact on outcome, factors associated with increased risk and risk stratification for bleeding, putative mechanisms through which bleeding impact on outcome, and bleeding-avoidance strategies to be used in the setting of PCI procedures.

Topics: Antithrombins; Hemorrhage; Hirudins; Humans; Incidence; Outcome Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Prognosis; Recombinant Proteins; Risk Adjustment; Risk Factors; Vascular Closure Devices

Bivalirudin significantly reduces 30-day major and minor bleeding compared with unfractionated heparin (UFH), while resulting in similar or lower rates of ischemic events in both patients with stable and unstable coronary disease undergoing percutaneous coronary intervention. We performed a meta-analysis of randomized trials to evaluate the impact of bivalirudin compared with UFH, with or without glycoprotein IIb/IIIa receptor inhibitors (GPI), on the rates of mortality, myocardial infarction (MI), and major bleeding.. We searched electronic databases for randomized controlled trials with >100 patients comparing bivalirudin (±provisional GPI) with UFH with either routine or provisional GPI in patients undergoing percutaneous coronary intervention. The principal efficacy end points were mortality and MI within 30 day, whereas major bleeding was the principal safety end point. We assessed the benefit of bivalirudin for each efficacy end point relative to the baseline bleeding risk, using the control (UFH) major bleeding rate as proxy for that risk.. A total of 12 randomized trials that enrolled 33,261 patients were included. Overall, there was no significant difference in mortality and MI between bivalirudin monotherapy and UFH (±GPI), whereas major bleeding was significantly lower with bivalirudin. Bivalirudin reduced major and minor bleeding across the entire bleeding risk spectrum.. Bivalirudin significantly reduces major and minor bleeding regardless of the estimated baseline hemorrhagic risk.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Regression Analysis; Treatment Outcome

Bivalirudin is an alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). We aimed to define the effects of a bivalirudin-based anticoagulation regimen compared with a heparin-based anticoagulation regimen on ischaemic and bleeding outcomes.. We searched Medline, the Cochrane Library, and relevant meeting abstracts (search done on April 9, 2014) for randomised trials that assessed bivalirudin versus heparin in patients planned for PCI. The primary efficacy endpoint was the incidence of major adverse cardiac events (MACE) up to 30 days. Secondary efficacy endpoints were death, myocardial infarction, ischaemia-driven revascularisation, and stent thrombosis. The primary safety endpoint was major bleeding up to 30 days. We calculated pooled risk ratios and 95% CIs using random-effects models.. We included data from 16 trials involving 33 958 patients, of whom 2422 experienced MACE and 1406 had a major bleed. There was an increase in the risk of MACE with bivalirudin-based regimens compared with heparin-based regimens (risk ratio 1·09, 95% CI 1·01-1·17; p=0·0204), which was largely driven by increases in myocardial infarction (1·12, 1·03-1·23) and seemingly also by ischaemia-driven revascularisation (1·16, 0·997-1·34) with bivalirudin compared with heparin, with no effect on mortality (0·99, 0·82-1·18). Bivalirudin increased the risk of stent thrombosis (risk ratio 1·38, 95% CI 1·09-1·74; p=0·0074), which was primarily due to an increase in acute cases in ST-segment elevation myocardial infarction (4·27, 2·28-8·00; p<0·0001). Overall, bivalirudin-based regimens lowered the risk of major bleeding (risk ratio 0·62, 95% CI 0·49-0·78; p<0·0001), but the magnitude of this effect varied greatly (p<0·0001) depending on whether glycoprotein IIb/IIIa inhibitors were used predominantly in the heparin arm only (0·53, 0·47-0·61; p<0·0001), provisionally in both arms (0·78, 0·51-1·19; p=0·25), or planned in both arms (1·07, 0·87-1·31; p=0·53).. Compared with a heparin-based regimen, a bivalirudin-based regimen increases the risk of myocardial infarction and stent thrombosis, but decreases the risk of bleeding, with the magnitude of the reduction depending on concomitant glycoprotein IIb/IIIa inhibitor use. Physicians should weigh the trade-off between ischaemic and bleeding events when choosing between different anticoagulant regimens.. None.

Topics: Anticoagulants; Antithrombins; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins

To investigate the relative benefits of unfractionated heparin, low molecular weight heparin(LMWH), fondaparinux, and bivalirudin as treatment options for patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI).. Mixed treatment comparison and direct comparison meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors.. A search of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) for randomized trials comparing unfractionated heparin plus glycoprotein IIb/IIIa inhibitor(GpIIb/IIIa inhibitor), unfractionated heparin, bivalirudin, fondaparinux, or LMWH plus GpIIb/IIIa inhibitor for patients undergoing primary PCI.. The primary efficacy outcome was short term (in hospital or within 30 days) major adverse cardiovascular event; the primary safety outcome was short term major bleeding.. We identified 22 randomized trials that enrolled 22,434 patients. In the mixed treatment comparison models, when compared with unfractionated heparin plus GpIIb/IIIa inhibitor, unfractionated heparin was associated with a higher risk of major adverse cardiovascular events (relative risk 1.49 (95% confidence interval 1.21 to 1.84), as were bivalirudin (relative risk 1.34 (1.01 to 1.78)) and fondaparinux (1.78 (1.01 to 3.14)). LMWH plus GpIIb/IIIa inhibitor showed highest treatment efficacy, followed (in order) by unfractionated heparin plus GpIIb/IIIa inhibitor, bivalirudin, unfractionated heparin, and fondaparinux. Bivalirudin was associated with lower major bleeding risk compared with unfractionated heparin plus GpIIb/IIIa inhibitor (relative risk 0.47 (0.30 to 0.74)) or unfractionated heparin (0.58 (0.37 to 0.90)). Bivalirudin, followed by unfractionated heparin, LMWH plus GpIIb/IIIa inhibitor, unfractionated heparin plus GpIIb/IIIa inhibitor, and fondaparinux were the hierarchy for treatment safety. Results were similar in direct comparison meta-analyses: bivalirudin was associated with a 39%, 44%, and 65% higher risk of myocardial infarction, urgent revascularization, and stent thrombosis respectively when compared with unfractionated heparin with or without GpIIb/IIIa inhibitor. However, bivalirudin was associated with a 48% lower risk of major bleeding compared with unfractionated heparin plus GpIIb/IIIa inhibitor and 32% lower compared with unfractionated heparin alone.. In patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of major adverse cardiovascular events, whereas bivalirudin was safest, with the lowest bleeding. These relationships should be considered in selecting anticoagulant therapies in patients undergoing primary PCI.

Topics: Anticoagulants; Antithrombins; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Integrin beta3; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Stents; Thrombosis; Treatment Outcome

A series of trials have shown that bivalirudin, a direct thrombin inhibitor that does not require the cofactor antithrombin III to be effective, is a reasonable alternative to unfractionated heparin (UFH) alone or associated with glycoprotein IIb/IIIa antagonists (GPI) in patients undergoing percutaneous coronary interventions (PCI). Particularly in patients with acute coronary syndromes (ACS), the effects of bivalirudin are striking. In the HORIZONS-AMI trial, patients with persistent ST-segment elevation (STEMI) had lower 30-day rates of net adverse clinical events and major bleeding, largely due to the significantly lower 30-day rate of non-coronary artery bypass grafting major bleeding. Bivalirudin also resulted in significantly lower rates of all-cause mortality and cardiac mortality, a benefit that extended up to 3-year follow-up. The beneficial effects of bivalirudin as compared to UFH associated with abciximab were also observed in 1721 non-ST elevation myocardial infarction (NSTEMI) patients undergoing PCI in the ISAR REACT 4 study. Although no difference was found between the two treatment strategies in the 30-day primary endpoint, bivalirudin use resulted in a lower rate of major bleeding. Despite the abundant evidence of benefit provided by bivalirudin in the treatment of ACS and the high level of recommendation received by the most recent Guidelines, its use is still low. The reasons for this underuse are multifactorial, the most likely being the preference of operators for the use of a low-cost agent, like UFH, that can be associated with a GPI. Countering platelet hyperreactivity is still the main goal of interventional cardiologists treating ACS patients invasively, apparently downplaying the pathogenetic role of thrombin in this clinical condition.

Topics: Acute Coronary Syndrome; Antithrombins; Coronary Artery Bypass; Drug Utilization; Evidence-Based Medicine; Hemorrhage; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Practice Patterns, Physicians'; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

Anticoagulant drugs belong to the group of antithrombotic agents and are successfully used in the prophylaxis and treatment of thromboembolic disorders. The use of anticoagulants in the prevention of deep venous thrombosis has significantly lowered the risk of venous thrombosis and fatal pulmonary embolisms even in high-risk situations such as orthopedic surgery. Anticoagulants play a central role in the treatment of acute venous thrombosis and in the prevention of recurrent events. Long-term anticoagulation therapy with orally active anticoagulants significantly reduces the risk of thromboembolic complications in patients showing cardiac arrhythmias. Whereas a few years ago heparins and vitamin K antagonists were the dominant anticoagulants, today a wide range of anticoagulants with improved pharmacological profiles are available. It remains an open question whether these new anticoagulants will improve the efficacy, safety, and acceptance of anticoagulant treatment approaches.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Arginine; Arrhythmias, Cardiac; Blood Coagulation Tests; Factor Xa Inhibitors; Hemorrhage; Heparin; Heparinoids; Hirudins; Humans; Infusions, Intravenous; Orthopedic Procedures; Peptide Fragments; Pipecolic Acids; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Risk Factors; Secondary Prevention; Sulfonamides; Thromboembolism; Treatment Outcome; Venous Thrombosis; Vitamin K

Bivalirudin (BVR) is a direct thrombin inhibitor used as an adjunctive antithrombotic agent in combination with aspirin and an ADP-receptor blocker in patients with acute coronary syndrome undergoing percutaneous coronary intervention. When compared to a strategy of heparin plus a glycoprotein IIb/IIIa inhibitor, BVR has been shown in a number of randomized clinical trials to be at least as effective at reducing ischemic endpoints and to have a consistently lower rate of bleeding complications. In addition, various economic analyses have shown it to be cost-effective compared to heparin plus a glycoprotein IIb/IIIa inhibitor and this, coupled with its proven clinical efficacy, has led to the incorporation of BVR into both EU and US clinical guidelines. Previous studies with BVR have mostly assessed its use in patients treated with aspirin and clopidogrel and further studies are ongoing to determine its role in combination with newer, more potent oral antiplatelet agents.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Cost-Benefit Analysis; Hemorrhage; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins

In-hospital mortality for ST-elevation myocardial infarction (STEMI) has declined thanks to a greater use of primary percutaneous coronary interventions (PCI) associated with more effective antiplatelet and anticoagulant drugs. In this regard, bivalirudin has been shown to decrease total and cardiac mortality as compared to unfractionated heparin (UFH).. The primary purpose of this analysis is to evaluate the hypothesis that the reduction of in-hospital bleeding is the most plausible explanation for the improved survival of STEMI patients treated with bivalirudin during primary PCI. The secondary objective is to reconsider the prognostic significance of the radial access alone or in association with bivalirudin on the basis of the published data.. We have done a comprehensive evaluation of the main and related publications of the HORIZONS-AMI trial in addition to an extensive research by Medline of randomized trials evaluating the prognostic impact of radial access as compared with the femoral one in primary PCI.. In the HORIZONS-AMI trial bivalirudin resulted in significantly lower rates of the 30 day primary endpoint (defined as major adverse ischemic outcomes plus major bleeding) over UFH plus GPI, largely due to the significantly lower rate of the protocol-defined major bleeding. All-cause and cardiac mortality were also reduced in the bivalirudin arm at 3 year follow-up. Recent studies have also shown that the use of the radial instead of the femoral approach for primary PCI is associated with reduced bleeding as well as reduced mortality.. Our research suggests that decreasing bleeding by either a pharmacologic strategy (use of bivalirudin) or a technical approach (the transradial access) improves survival in STEMI patients undergoing primary PCI. The validity of this hypothesis should be confirmed by specific randomized trials.

Topics: Anticoagulants; Antithrombins; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins

Various limitations of unfractionated heparin (UFH) have triggered a search for new antithrombotic therapies for patients with coronary artery disease (CAD). Bivalirudin is a direct thrombin inhibitor with several pharmacological advantages over UFH and is currently endorsed by practice guidelines, particularly in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). To maximize effectiveness of an antithrombotic regimen and reduce complications, both ischemic and bleeding risks should be known when an antithrombotic strategy is chosen.. This review focuses on the safety and tolerability of bivalirudin in patients with CAD in the setting of currently approved indications. Synthesis of evidence has been made from clinical trials, systematic reviews, meta-analyses and registries (1992 - 2011). The reader is provided with an overview of pharmacological properties of bivalirudin and its efficacy, with special emphasis on its safety in patients with CAD.. Bivalirudin has an impressive safety profile in CAD patients treated with PCI. Bivalirudin is the antithrombotic of choice in suspected or verified heparin-induced thrombocytopenia. For ST elevation myocardial infarction patients undergoing primary PCI, bivalirudin should become the preferred antithrombotic agent together with early institution of antiplatelet therapy.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Coronary Artery Disease; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Practice Guidelines as Topic; Recombinant Proteins; Thrombocytopenia

Cardiovascular disease is the leading cause of death in the US. For patients with ST-elevation myocardial infarction (STEMI), urgent reperfusion of the culprit arterial occlusion, often achieved via primary percutaneous coronary intervention (PCI), reduces post-MI mortality and other major adverse cardiovascular events (MACE). Adjunctive antithrombotic and antiplatelet therapies are used during PCI to reduce MACE rates. Currently, a variety of antithrombotic options are available for peri-procedural use. The most commonly used agents include unfractionated heparin or low molecular weight heparin ± glycoprotein IIb/IIIa inhibitors (GPI). These agents reduce the rates of peri-procedural ischemic and thrombotic events, though these benefits come at the cost of an increase in bleeding complications. Bivalirudin is a direct thrombin inhibitor with a short half-life and linear pharmacokinetics, which results in predictable serum concentrations and anticoagulant effect. Bivalirudin has emerged as an efficacious and safe alternative to heparin plus GP IIb/IIIa inhibitors in both stable coronary artery disease and acute coronary syndrome patients. In the HORIZONS-AMI trial, monotherapy with bivalirudin was compared with the combination of heparin and a GPI in a large population of patients with STEMI who underwent primary PCI. Bivalirudin treatment was associated with improved event-free survival at 30 days and reduced rates of major bleeding. Based on the results of the trial, the American College of Cardiology/American Heart Association and European Society of Cardiology guidelines have incorporated recommendations for bivalirudin use in the setting of STEMI. Recently, 3-year follow-up data from the HORIZONS-AMI cohort were published, demonstrating sustained benefits in patients treated with bivalirudin, including reduced rates of mortality, cardiovascular mortality, reinfarction, and major bleeding events. These results further support the use of bivalirudin in the setting of primary PCI for STEMI given that its benefits are maintained through long-term follow-up.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Disease-Free Survival; Drug Therapy, Combination; Evidence-Based Medicine; Hemorrhage; Heparin; Hirudins; Humans; Multicenter Studies as Topic; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Secondary Prevention; Time Factors; Treatment Outcome

To describe the hazard of in-hospital major bleeding after acute coronary syndromes.. Long-term complications of early bleeding can extend to over 3 years beyond the index event. Nonaccess-site bleeding accounts for much of the higher risk associated with major in-hospital bleeding.. Bleeding complications after percutaneous coronary intervention are a consistent and independent predictor of adverse clinical outcomes. The majority of complications associated with major bleeding are attributable to in-hospital early bleeds. Whether the link between bleeding and increased mortality is causal has not been established. Bleeding may simply be a marker of higher comorbidity. When possible, bleeding should be avoided, and strategies such as use of risk scores, bivalirudin, vascular closure devices and radial access may decrease major bleeding. In the highest-risk patients, however, bleeding avoidance strategies may not be effective.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Hemorrhage; Hirudins; Hospitalization; Humans; Peptide Fragments; Recombinant Proteins; Risk Factors; Treatment Outcome

The optimal antithrombotic therapy for patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention is not well defined. We investigated the efficacy and safety of bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment.. This study included 3798 clopidogrel-pretreated patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention, who were randomly assigned to receive bivalirudin (n=1928) or heparin (unfractionated heparin or enoxaparin; n=1870) plus a GPI in the setting of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) and Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 4 trials. Major end points were a composite of death, recurrent myocardial infarction or urgent target vessel revascularization (efficacy end point), major bleeding (safety end point), and the composite of death, recurrent myocardial infarction, urgent target vessel revascularization, or major bleeding (net adverse clinical events [NACE]) at 30 days. The incidence of the efficacy end point was 10.6% (n=205) in the bivalirudin group versus 10.2% (n=191) in the heparin plus a GPI group (OR, 1.04; 95% CI, 0.85-1.27; P=0.69). The incidence of safety end point was 3.4% (n=66) in the bivalirudin group versus 6.3% (n=117) in the heparin plus a GPI group (OR, 0.54 [0.40-0.72]; P<0.001). NACE occurred in 258 patients (13.4%) in the bivalirudin group versus 275 patients (14.7%) in the heparin plus a GPI group (OR, 0.90 [0.76-1.06]; P=0.21).. NACE rates were not significantly different between bivalirudin and heparin plus a GPI in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment. Although no significant difference in efficacy was seen in terms of suppression of adverse ischemic events, bivalirudin was superior to heparin plus a GPI in terms of reducing bleeding events.. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00093158 and NCT00373451.

Topics: Aged; Chi-Square Distribution; Coronary Thrombosis; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Risk Factors; Treatment Outcome

The aim of this study was to evaluate the relative frequency of access and nonaccess site bleeding, the association of these events with 1-year mortality, and the impact of randomized antithrombotic therapy.. Post-percutaneous coronary intervention (PCI) bleeding has been strongly associated with subsequent mortality. The extent to which access versus nonaccess site bleeding contributes to this poor prognosis and the role of antithrombotic therapies remains poorly understood.. The incidence and impact of Thrombolysis In Myocardial Infarction (TIMI) major/minor 30-day bleeding and randomized antithrombotic therapy were examined in a combined dataset from the REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events), Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY), and HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trials in 17,393 PCI patients.. The TIMI major/minor bleeding occurred in 5.3% of patients, 61.4% of which (3.3%) were nonaccess site bleeds. After multivariable adjustment, TIMI bleeding was associated with an increased risk of 1-year mortality (hazard ratio [HR]: 3.17, 95% confidence interval [CI]: 2.51 to 4.00, p < 0.0001). The HR of a nonaccess site bleed was approximately 2-fold that of an access site bleed: HR: 3.94, 95% CI: 3.07 to 5.15, p < 0.0001 versus HR: 1.82, 95% CI: 1.17 to 2.83, p = 0.008, respectively. Randomization to bivalirudin versus heparin + a glycoprotein IIb/IIIa inhibitor resulted in 38% and 43% relative reductions in TIMI major/minor and TIMI major bleeding, respectively (p < 0.0001 for both), with significant reductions in both access and nonaccess site bleeding.. Nonaccess site bleeding after PCI is common, representing approximately two-thirds of all TIMI bleeding events, and is associated with a 4-fold increase in 1-year mortality. Use of bivalirudin rather than heparin + a glycoprotein IIb/IIIa inhibitor significantly decreases both nonaccess site as well as access site bleeding events by approximately 40%.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Proportional Hazards Models; Punctures; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors

Recent studies have highlighted the critical importance of bleeding complications on prognosis in patients with acute coronary syndromes (ACS). In fact, the hazard for an adverse cardiovascular event associated with bleeding is similar to that of a myocardial infarction. Several bleeding risk scores are now available that reliably quantify the probability of an ACS patient experiencing a bleeding complication. Consistent and strong correlates of bleeding include older age, female sex, renal impairment, and an invasive management approach. Although patients who tend to bleed are usually more morbid compared with their non-bleeding counterparts, several lines of experimental and clinical evidence suggest an independent and causal pathway for bleeding-associated cardiovascular risk. Given the frequency and adverse prognosis associated with bleeding, interventions that might reduce such complications are now a major emphasis in the current era of ACS treatment. Recent trials have shown that several novel antithrombotics, bivalirudin and fondaparinux, reduce bleeding risk while maintaining efficacy in reducing ischemic events during ACS. Other promising strategies that continue to be tested include the use of vascular closure devices and transradial arterial access during percutaneous coronary intervention.

Topics: Acute Coronary Syndrome; Anticoagulants; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Hirudins; Humans; Incidence; Peptide Fragments; Platelet Aggregation Inhibitors; Polysaccharides; Prognosis; Recombinant Proteins; Risk Assessment; Risk Factors

Direct thrombin inhibitors (DTIs) are an emerging class of anticoagulants in routine clinical practice, although they have been under investigation for quite some time. Desirudin (Iprivask®, Canyon Pharmaceuticals™) is a recombinant hirudin derivative that directly inhibits free and fibrin-bound thrombin. Desirudin was the first DTI approved for deep vein thrombosis (DVT) prophylaxis in Europe (Revasc®) and is the newest injectable DTI commercially available in the USA. Desirudin is one of the few nonheparin subcutaneous drugs that has demonstrable efficacy for DVT prophylaxis. Subcutaneous desirudin has been shown to be more effective than both subcutaneous unfractionated heparin and enoxaparin, with comparable bleeding rates in the prevention of DVT in patients undergoing elective hip replacement. Desirudin also offers the advantage of a fixed dosing regimen while being less immunogenic than unfractionated heparin. However, owing to its pharmacokinetic properties, patients with renal dysfunction require dosing modifications. The favorable profile shown with desirudin thus far will allow its clinical use to grow and will promote further investigation into broadening its clinical applications.

Topics: Animals; Anticoagulants; Antithrombins; Dose-Response Relationship, Drug; Hemorrhage; Hirudins; Humans; Recombinant Proteins; Renal Insufficiency; Venous Thrombosis

This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Cerebral Hemorrhage; Hemorrhage; Hirudins; Humans; Peptide Fragments; Protein C; Recombinant Proteins; Vitamin K; von Willebrand Factor

Chronic kidney disease (CKD) is prevalent and affects an ever-increasing proportion of patients presenting with acute coronary syndrome (ACS). Patients with CKD have a higher risk of ACS and significantly higher mortality, and are also predisposed to increased bleeding complications. Antiplatelet and antithrombotic drugs form the bedrock of management of patients with ACS. Most randomized trials of these drugs exclude patients with CKD, and current guidelines for management of these patients are largely based on these trials. We aim to review the safety and efficacy of these drugs in patients with CKD presenting with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Chronic Disease; Clinical Trials as Topic; Clopidogrel; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine; Uremia

To perform a thorough and updated systematic review of randomized clinical trials comparing tirofiban vs. placebo or vs. abciximab.. We searched for randomized trials comparing tirofiban vs. placebo or any active control. Odds ratios (OR) were computed from individual studies and pooled with random-effect methods. Thirty-one studies were identified involving 20,006 patients (12 874 comparing tirofiban vs. heparin plus placebo or bivalirudin alone, and 7132 vs. abciximab). When compared with placebo, tirofiban was associated at 30 days with a significant reduction in mortality [OR = 0.68 (0.54-0.86); P = 0.001] and death or myocardial infarction (MI) [OR = 0.69 (0.58-0.81); P < 0.001]. The treatment benefit persisted at follow-up but came at an increased risk of minor bleedings [OR = 1.42 (1.13, 1.79), P = 0.002] or thrombocytopenia. When compared with abciximab, mortality at 30 days did not differ [OR = 0.90 (0.53, 1.54); P = 0.70], but in the overall group tirofiban trended to increase the composite of death or MI [OR = 1.18 (0.96, 1.45); P = 0.11]. No such trend persisted at medium-term follow-up or when appraising studies testing tirofiban at 25 microg/kg bolus regimen.. Tirofiban administration reduces mortality, the composite of death or MI and increases minor bleedings when compared with placebo. An early ischaemic hazard disfavouring tirofiban was noted when compared with abciximab in studies based on 10 but not 25 microg/kg tirofiban bolus regimen.

Topics: Abciximab; Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Chemotherapy, Adjuvant; Hemorrhage; Hirudins; Humans; Immunoglobulin Fab Fragments; Peptide Fragments; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Regression Analysis; Tirofiban; Tyrosine

Antithrombotic therapy constitutes the basis of the management of acute coronary syndromes. It combines antiplatelet and anticoagulant therapy. Antiplatelet agents should combine aspirin and agents acting through the ADP pathway such as clopidogrel; newer antiplatelet agents such as prasugrel or ticagrelor have superior anti-ischemic efficacy, compared with clopidogrel. Intravenous glycoprotein IIb/IIIa inhibitors may be used in selected patients at high risk undergoing percutaneous coronary interventions. Unfractionated heparin constitutes the reference anticoagulant treatment. Enoxaparin provides slightly better anti-ischemic efficacy. Newer agents, such as bivalirudin or fondaparinux, reduce bleeding complications, with no improvement in anti-ischemic efficacy. The combination of antiplatelet and anticoagulant agents should be chosen according to the patients' characteristics and the management strategy of the acute coronary syndrome.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Disease Management; Drug Synergism; Drug Therapy, Combination; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine

Bivalirudin is a direct thrombin inhibitor with several pharmacological advantages over heparin. It has been studied extensively in non-ST elevation acute 60 coronary syndromes (NSTE-ACS) and in percutaneous coronary intervention. Bivalirudin has also recently been investigated in patients with ST-elevation myocardial infarction (STEMI) treated with primary angioplasty and stenting. More than 27,000 patients were randomized in these trials.. To provide an overview of the pharmacological properties of bivalirudin and its efficacy and safety profile in patients across the spectrum of acute coronary syndromes (ACS).. All published, peer-reviewed clinical trials were reviewed and as relevant were included.. Bivalirudin with provisional IIb/IIIa antagonists provides consistent results across the full spectrum of ACS, with similar or non-inferior protection from ischemic events and significantly reduces bleeding complications compared with heparin and IIb/IIIa antagonists. In STEMI, mortality at 30 days and 1 year is significantly reduced. The unique pharmacokinetic profile of bivalirudin allows for simultaneous reductions in both ischemic and hemorrhagic events and makes it an appropriate alternative to heparin.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Cost-Benefit Analysis; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombin

Patients who present with acute coronary syndromes, particularly ST-segment elevation myocardial infarction (STEMI), have abnormalities in platelet size and function that predispose to thrombotic events. Both preprocedural platelet reactivity and mean platelet volume are directly correlated with the occurrence of adverse ischemic events and impaired microvascular reperfusion following primary percutaneous coronary intervention (PCI) for STEMI. The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial demonstrated a similar ischemic event rate to 30 days with a significantly lower bleeding event rate (enhanced net clinical benefit) in favor of bivalirudin monotherapy (with provisional platelet glycoprotein [GP] IIb/IIIa receptor blockade) in comparison with unfractionated heparin plus GP IIb/IIIa blockade in patients undergoing primary PCI for STEMI. The bivalirudin monotherapy was associated with a highly significant greater incidence of acute stent thrombosis. This observation provides the opportunity for strategies that enhance periprocedural platelet inhibition to reduce stent thrombosis and to potentially improve the safety and efficacy of periprocedural adjunctive pharmacotherapy above that achieved by bivalirudin monotherapy alone.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Chemotherapy, Adjuvant; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Thiophenes; Thrombosis; Ticlopidine; Time Factors; Treatment Outcome

Appropriate pharmacologic treatment for patients with acute coronary syndromes (ACS) remains a matter of controversy. Additionally, a substantial gap exists between recommended guidelines and current clinical practice. Questions remain regarding which antiplatelet/antithrombotic treatment strategies are appropriate for individual patients, based on their risk. We explore the role of glycoprotein IIb-IIIa inhibitors and the direct thrombin inhibitor bivalirudin in ACS patients, and consider the difficulties involved in reducing ischemic events while limiting bleeding risks. In patients with ACS who are undergoing percutaneous coronary intervention, high levels of microembolization and myocardial necrosis are potential risk factors for adverse long-term outcomes. Intensive antiplatelet/antithrombotic regimens may substantially affect these factors. Determination of risk levels, with the goal of targeting aggressive antithrombotic and interventional therapies to patients at higher risk, will help physicians choose appropriate pharmacologic therapy for patients with ACS.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Antithrombins; Aspirin; Clopidogrel; Enoxaparin; Eptifibatide; Fibrinolytic Agents; Heart Conduction System; Hemorrhage; Heparin; Hirudins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Risk Factors; Ticlopidine

The options for drug-controlled anticoagulation are becoming noticeably more manifold. In the area of anaesthesiology and intensive care, there are furthermore special disease patterns, such as heparin-induced thrombocytopenia (HIT) to be known, diagnosed and treated. This article gives a review of the substance groups of the direct thrombin inhibitors (DTI) as alternative anticoagulants for HIT in combination with cardiovascular diseases. For the administration of DTIs, experience and the correct dose are the keys to success and are the deciding factors for the two sides of haemostasis: thrombosis and haemorrhage.

Topics: Anesthesia; Anticoagulants; Cardiovascular Surgical Procedures; Critical Care; Hemorrhage; Hemostasis; Heparin; Heparin Antagonists; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombin; Thrombosis

This review discusses the pharmacology and clinical applications of hirudin, a bivalent direct thrombin inhibitor (DTI). Besides the current major indication for hirudin--anticoagulation of patients with heparin-induced thrombocytopenia (HIT)--the experience with hirudin in other indications, especially acute coronary syndromes, are briefly presented. Hirudins have been formally studied prior to their regulatory approval; however, important information on their side effects and relevant preventative measures only became available later. Therefore, current recommendations and dosing schedules for hirudin differ considerably from the information given in the package inserts. Drawbacks of hirudin and important precautions for avoiding potential adverse effects are discussed in detail in the third part of this review.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Cardiopulmonary Bypass; Drug Monitoring; Fibrinolytic Agents; Hemorrhage; Hemostasis, Surgical; Heparin; Hirudin Therapy; Hirudins; Humans; Prothrombin; Renal Dialysis; Thrombin; Thrombocytopenia; Thrombosis; Vascular Surgical Procedures

Bivalirudin is a direct thrombin inhibitor (DTI) frequently used for anticoagulation in the setting of invasive cardiology, particularly percutaneous coronary intervention (PCI). Bivalirudin has a unique pharmacologic profile: unlike other marketed DTIs, it undergoes predominant non-organ elimination (proteolysis), and has the shortest half-life (approximately 25 min). Its affinity for thrombin is intermediate between that of lepirudin (highest) and argatroban (lowest)--this helps explain why it interferes with functional clotting assays to an extent intermediate between that achieved by these two other DTIs. This effect is best known for the PT (INR)--higher affinity for thrombin corresponds to lower molar DTI requirements to prolong the APTT; in turn, lower concentrations required for APTT prolongation (and, presumably, in-vivo effect) result in reduced PT (INR) prolongation. Bivalirudin is primarily used for its first FDA-approved indication, namely anticoagulation during percutaneous transluminal coronary angioplasty ("balloon angioplasty"), the most frequent type of PCI. Bivalirudin is also indicated for PCI with provisional use of glycoprotein IIb/IIIa antagonist therapy, and for patients with, or at risk of, heparin-induced thrombocytopenia (HIT), or HIT with thrombosis syndrome (HITTS), undergoing PCI. The bivalirudin development program has used a "quadruple" endpoint comprising a "triple" efficacy endpoint plus major bleeding - this approach anticipated the subsequent emphasis on strategies to improve clinical outcomes through bleeding reduction. Besides summarizing the key trials evaluating bivalirudin use for acute coronary syndrome (especially employing PCI), we review also the studies of bivalirudin as anticoagulant for "on-" and "off-pump" cardiac surgery, including both HIT and non-HIT situations.

Topics: Acute Coronary Syndrome; Amino Acid Sequence; Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Blood Coagulation; Cardiac Surgical Procedures; Fibrinolytic Agents; Hemorrhage; Hemostasis, Surgical; Heparin; Hirudins; Humans; Molecular Sequence Data; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Thrombocytopenia; Thrombosis

Antithrombotic and powerful antiplatelet therapies, in addition to early percutaneous coronary intervention (PCI) are considered the treatment of choice for moderate- to high-risk patients with acute coronary syndromes (ACS; unstable angina and non-ST-segment elevation myocardial infarction). However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors (GPI), and thienopyridines, the rate of adverse ischemic events still remains unacceptably high. Intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty as well as surgical revascularization procedures, elicit a high rate of bleeding complications. Recent trials (ACUITY and HORIZONS studies) added evidence regarding safety and efficacy of bivalirudin use in acute coronary syndromes. In summary, is has been shown that bivalirudin alone is safe and effective in the vast majority of patients suffering from acute coronary syndromes and being treated invasively. The cost-effectiveness of such an approach will have to be determined. It remains to be a matter of discussion whether there are still patient subgroups being in need of more aggressive treatment strategies including GPI. In practice, it might be reasonable to perform a baseline assessment of hemorrhagic risk facilitating the choice of an antithrombotic regimen with a favourable safety and efficacy profile. With this tailored therapy it might be possible to further improve outcomes for individual patients with ACS.

Topics: Acute Coronary Syndrome; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

Patients with or at risk of heparin-induced thrombocytopenia (HIT) who are undergoing percutaneous coronary intervention (PCI) are at particular risk of thrombosis due to the prothrombotic nature of HIT and the endovascular disruption from PCI. Patients require aggressive anticoagulation during PCI, and alternative, nonheparin anticoagulation is recommended over heparin in patients with acute or previous HIT. Argatroban, bivalirudin, and lepirudin are nonheparin, fast-acting, parenteral direct thrombin inhibitors (DTIs). Multicenter, prospective studies have demonstrated that argatroban and lepirudin each reduce thrombosis in HIT and that argatroban and bivalirudin each provide adequate anticoagulation during PCI in patients with or at risk of HIT. We review current therapeutic practices with direct thrombin inhibitors in patients with or at risk of HIT during PCI, including individuals requiring periprocedural anticoagulation, and the factors influencing the choice of DTI in this setting.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Arginine; Drug Interactions; Economics, Pharmaceutical; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombosis

Numerous acquired hemostatic abnormalities have been identified in renal insufficiency. Hemodialysis procedures add to these disturbances as they repetitively imply turbulent blood flow, high shear stress, and contact of blood to artificial surfaces. This nonphysiological environment leads to activation of platelets, leukocytes, and the coagulation cascade, resulting in fouling of the membrane and ultimately in clotting of fibers and the whole hemodialyzer. Anticoagulation in hemodialysis is targeted to prevent this activation of coagulation during the procedure. Most agents inhibit the plasmatic coagulation cascade. Still commonly used is unfractionated heparin, followed by low-molecular-weight heparin preparations with distinct advantages. Immune-mediated heparin-induced thrombocytopenia constitutes a potentially life-threatening complication of heparin therapy requiring immediate switch to nonheparin alternative anticoagulants. Danaparoid, lepirudin, and argatroban are currently being used for alternative anticoagulation, all of which possess both advantages and limitations. In the past, empirical strategies reducing or avoiding heparin were applied for patients at bleeding risk, whereas nowadays regional citrate anticoagulation is increasingly used to prevent bleeding by allowing procedures without any systemic anticoagulation. Avoidance of clotting within the whole hemodialyzer circuit is not granted. Specific knowledge of the mechanisms of coagulation, the targets of the anticoagulants in use, and their respective characteristics constitutes the basis for individualized anticoagulation aimed at achieving full patency of the circuit throughout the procedure. Patency of the circuit is an important prerequisite for optimal hemodialysis quality.

Topics: Anticoagulants; Arginine; Blood Coagulation; Chondroitin Sulfates; Dermatan Sulfate; Equipment Failure; Hemorrhage; Heparin; Heparitin Sulfate; Hirudins; Humans; Pipecolic Acids; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Sulfonamides

Topics: Angina, Unstable; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Brain Ischemia; Clinical Trials as Topic; Coumarins; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Forecasting; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Morpholines; Myocardial Infarction; Peptide Fragments; Polysaccharides; Prothrombin; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Thrombosis; Warfarin

Heparin-induced thrombocytopenia (HIT) is a potentially devastating immune mediated adverse drug reaction caused by the emergence of antibodies that activate platelets in the presence of heparin. Despite thrombocytopenia, bleeding is rare; rather, HIT is strongly associated with thromboembolic complications involving both the arterial and venous systems. A number of laboratory tests are available to confirm the diagnosis; however, when HIT is clinically suspected, treatment should not be withheld pending the result. Fortunately, therapeutic strategies have been refined, and new and effective therapeutic agents are available. Treatment options are focused on inhibiting thrombin formation or direct thrombin inhibition. Warfarin should not be used until the platelet count has recovered.

Topics: Anticoagulants; Arginine; Cardiovascular Surgical Procedures; Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Hemorrhage; Heparin; Heparitin Sulfate; Hirudins; Humans; Pipecolic Acids; Recombinant Proteins; Renal Dialysis; Sulfonamides; Thrombocytopenia; Warfarin

The anticoagulant properties of heparin were discovered in 1916, and by the 1930s researchers were evaluating its therapeutic use in clinical trials. Treatment of unstable angina with unfractionated heparin (UFH), in addition to aspirin, was introduced into clinical practice in the early 1980s. UFH was combined with aspirin to suppress thrombin propagation and fibrin formation in patients presenting with acute coronary syndromes (ACS) or patients undergoing percutaneous coronary intervention (PCI). However, UFH stimulates platelets, leading to both activation and aggregation, which may further promote clot formation. Clinical trials have demonstrated that newer agents, such as the low-molecular-weight heparins (LMWHs), are superior to UFH for medical management of unstable angina or non-ST-segment elevation myocardial infarction. Increasingly, the LMWHs have been used as the anticoagulant of choice for patients presenting with ACS. For patients undergoing PCI, LMWH provides no sub-stantial benefit over UFH for anticoagulation; however, direct thrombin inhibitors (DTIs) have demonstrated safety and efficacy in this setting. UFH is likely to be replaced by more effective and safer antithrombin agents, such as DTIs. DTIs have antiplatelet effects, anticoagulant action, and most do not bind to plasma proteins, thereby providing a more consistent dose-response effect than UFH. The FDA has approved 4 parenteral DTIs for various indications: lepirudin, argatroban, bivalirudin, and desirudin. The antiplatelet, anticoagulant, and pharmacokinetic properties of bivalirudin support its use as the anticoagulant of choice for both lower- and higher-risk patients, including those undergoing PCI.

Topics: Acute Disease; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Models, Molecular; Molecular Structure; Myocardial Ischemia; Peptide Fragments; Pipecolic Acids; Platelet Activation; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thrombosis

Recent data suggest that bivalirudin, a reversible direct thrombin inhibitor, may be noninferior to heparins (unfractionated heparin/low molecular weight heparin) in providing protection against cardiovascular events, with significantly fewer bleeding complications. Whether this advantage is consistent has not been fully defined. We evaluated cardiac outcomes with bivalirudin vs the heparins in management of acute coronary syndromes (ACS), including patients undergoing percutaneous coronary interventions (PCI). Formal computer-aided searches of electronic databases (MEDLINE, PubMed, Cochrane Controlled Trials Registry) were performed by scrutiny of the reference lists of trials and review articles, abstracts, meeting proceedings, and the manufacturers of direct thrombin inhibitors. Five randomized controlled trials (BAT, 1995; CACHET, 2002; REPLACE-2, 2003; REPLACE-1, 2004; and ACUITY, 2006) comparing bivalirudin to the heparins in patients with ACS, including patients undergoing PCI, were identified. The meta-analysis consisted of 25 457 patients (bivalirudin, 15 077; heparins, 10 380). The primary safety end point was major bleeding, defined as intracranial, intraocular, or retroperitoneal hemorrhage; clinically overt blood loss leading to a hemoglobin drop exceeding 3 g/dL (or 10% of hematocrit) and transfusion of 2 or more units of whole blood or packed red blood cells. The combined relative risks (RR) across all of the studies and the 95% confidence intervals of death, myocardial infarction (MI), and revascularization (bivalirudin vs heparins) were computed using the Mantel-Haenszel fixed-effect model, whereas the random-effect model was used for major bleeding. A 2-sided alpha error < .05 was considered to be significant. There were no significant differences in patient characteristics between the 2 groups. Compared to the heparins, the risk of death, MI, revascularization, and composite ischemic end points were similar with bivalirudin monotherapy. However, the risk of major bleeding was significantly lower with bivalirudin use (RR = 0.553; 95% CI = 0.402-0.761; P = .001). The present meta-analysis suggests that bivalirudin may be noninferior to the heparins in reducing the composite of ischemic end points. Additionally, compared to the heparins, bivalirudin monotherapy may lower the rate of major bleeding.

Topics: Acute Coronary Syndrome; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Bivalirudin is a direct thrombin inhibitor that has biological and pharmacokinetic advantages over heparin, e.g., by inhibiting both fibrin-bound and -unbound thrombin. In patients undergoing subacute or elective percutaneous coronary intervention, bivalirudin + provisional glycoprotein IIb/IIIa inhibition is as effective as unfractionated heparin + glycoprotein IIb/IIIa inhibition and is associated with a reduced risk of bleeding. The results of ongoing trials will further define the promising role of bivalirudin in the treatment of patients with acute coronary syndromes.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Hemorrhage; Hirudins; Humans; Intraoperative Complications; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

Bivalirudin is a member of the direct thrombin inhibitor group of anticoagulants. It has been evaluated as an alternative to unfractionated and low-molecular-weight heparins in the settings of percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS). Results of clinical trials to date suggest bivalirudin is a viable alternative to the use of a heparin combined with a glycoprotein (GP) IIb/IIIa inhibitor in these settings. Thrombin has a central role in coagulation and platelet activation in ACS and during PCI. Its direct inhibition is an attractive target for therapy in these settings. Bivalirudin is a 20 amino acid polypeptide hirudin analog. It displays bivalent and reversible binding to the thrombin molecule, inhibiting its action. Direct inhibition of thrombin with bivalirudin has theoretical pharmacokinetic and pharmacodynamic advantages over the indirect anticoagulants. A reduction in rates of bleeding without loss of anti-thrombotic efficacy has been a consistent finding across multiple clinical trials. There may be economic benefits to the use ofbivalirudin if it permits a lower rate of use of the GP IIb/IIIa inhibitors. This article reviews the pharmacology of bivalirudin and clinical trial evidence to date. There are now data from multiple clinical trials and meta-analyses in the setting of ACS and PCI. Early results from the acute catheterization and urgent intervention strategy (ACUITY) trial are discussed.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins; Secondary Prevention; Syndrome; Thrombin; Thrombosis

To assess efficacy and safety of lepirudin in patients with heparin-induced thrombocytopenia (HIT) in a prospective study (HAT-3) as well as in a combined analysis of all HAT study data.. Patients with laboratory-confirmed HIT were treated with lepirudin in three different aPTT-adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic complications (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison.. After start of lepirudin in 205 patients treated in HAT-3, the combined endpoint occurred in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occurred. Major bleeding occurred in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start of lepirudin treatment, the combined endpoint occurred in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with the historical control group (log-rank test), the combined endpoint after start of treatment was reduced (29.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg(-1) h(-1). Major bleeding was more frequent in the lepirudin-treated patients (29.4% vs. 9.1%, P = 0.0148).. The rate of new TECs in HIT patients is low after start of lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg(-1) h(-1).

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Secondary Prevention; Survival Analysis; Thrombocytopenia; Thromboembolism

Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal activated clotting time (ACT) for prevention of ischemic or hemorrhagic complications.. We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (P=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value, P=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with higher rates of events. The incidence of major or minor bleeding at 48 hours, by ACT quartile, was 2.9%, 3.5%, 3.8%, and 4.0%, respectively (P=0.04 for trend). In a multivariable logistic model with a spline transformation for ACT, there was a linear increase in risk of bleeding as the ACT approached 365 seconds (P=0.01), which leveled off beyond that value. Increasing UFH weight-indexed dose was independently associated with higher bleeding rates (OR 1.04 [1.02 to 1.07] for each 10 U/kg, P=0.001).. In patients undergoing PCI with frequent stent and potent platelet inhibition use, ACT does not correlate with ischemic complications and has a modest association with bleeding complications, driven mainly by minor bleeding. Lower values do not appear to compromise efficacy while increasing safety.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Aspirin; Blood Coagulation Tests; Clopidogrel; Comorbidity; Coronary Restenosis; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Stents; Thrombophilia; Ticlopidine; Tirofiban; Tyrosine

Heparin-induced thrombocytopenia (HIT) is a serious and common complication of heparin therapy that can lead to significant losses of life and limb. It is often under-recognized and, therefore, goes untreated until thrombosis develops. This article is meant to provide specific recommendations for treating patients with immune-mediated HIT, whether or not it is associated with thrombosis. These recommendations are based on our clinical experience treating patients with HIT and our evaluation of the published data on the efficacy and safety of lepirudin and argatroban, the 2 drugs approved by the Food and Drug Administration for treating HIT. Based on these criteria, we consider lepirudin the treatment of choice in all patients with HIT except those with severe or deteriorating renal function.

Topics: Algorithms; Anticoagulants; Antigen-Antibody Complex; Arginine; Clinical Trials as Topic; Diagnosis, Differential; Disease Management; Follow-Up Studies; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Immunoglobulin G; Pipecolic Acids; Platelet Activation; Platelet Count; Platelet Factor 4; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombophilia; Time Factors

Routine haemodialysis is performed with systemic anticoagulation, usually with heparin, to prevent thrombosis in the extracorporeal blood circuit. However, systemic anticoagulation can produce haemorrhagic complications in patients at high risk of bleeding. To minimize the risk of bleeding, a number of alternative regimens have been proposed: regional heparinization with protamine reversal; minimal heparinization; no heparin with saline flushes; regional anticoagulation with citrate; or prostacyclin anticoagulation. Although the incidence of bleeding complications has been reduced, each of these methods has its own limitations and complications. Among the types of membrane used in dialysers, cellulose membranes have been made more biocompatible by attaching N,N-diethyl-aminoehtyl (DEAE) groups to cellulose backbone. Positively charged DEAE groups on Hemophan enable negative charged heparin to be bound with the membrane. Haemodialysis using heparin-bound Hemophan has been reported to be a possible modality for patients at risk of bleeding. We designed more simplified heparin binding technique and have performed haemodialysis using heparin-bound Hemophan in patients at risk of bleeding during the past 7 years. In this review, current strategies to minimize bleeding complications and our experience of haemodialysis using heparin-bound Hemophan will be discussed.

Topics: Anticoagulants; Cellulose; Citrates; Epoprostenol; Hemodialysis Solutions; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Membranes, Artificial; Recombinant Proteins; Renal Dialysis; Risk Factors; Sodium Citrate

The treatment of patients with acute coronary syndromes has changed dramatically over the last several years. Most patients now undergo some form of percutaneous coronary intervention (PCI), which includes either stent placement or percutaneous transluminal coronary angioplasty (PTCA). Along with new medical interventions for acute coronary syndromes comes the need for new antithrombotic therapies. Combination therapy with antiplatelet agents (aspirin, adenosine diphosphate inhibitors), glycoprotein (GP) IIb-IIIa receptor inhibitors, and anticoagulants (unfractionated heparin or low-molecular-weight heparins) is administered, depending on the type of intervention and severity of the coronary lesion. Bivalirudin is a direct thrombin inhibitor that recently was approved as an alternative to heparin in patients undergoing PTCA. Compared with unfractionated heparin, bivalirudin reduces the rate of death, myocardial infarction, or revascularization, with a concurrent reduction in bleeding. This agent offers promise as a replacement for unfractionated heparin in PCI and is being studied in comparison with unfractionated heparin plus GP IIb-IIIa receptor inhibitors in patients undergoing intracoronary stent placement.

Topics: Angioplasty, Balloon, Coronary; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombin; Thrombocytopenia; Thrombosis; Treatment Outcome

Topics: Anticoagulants; Coumarins; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Preoperative Care; Purinergic P2 Receptor Antagonists; Risk Factors; Thrombosis; Thromboxane A2

Heparin-induced thrombocytopenia (HIT) may be complicated by severe thrombotic complications and death. Currently no specific laboratory test is available to make the diagnosis. When HIT is clinically suspected, heparin should be discontinued immediately. While no specific therapy for HIT exists, there is increasing evidence that acute antithrombin therapy may significantly reduce morbidity and mortality. Among several agents, the direct antithrombins, such as r-hirudin and argatroban, look the most promising for acute treatment.

Topics: Ancrod; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Forecasting; Gangrene; Hemorrhage; Heparin; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Pipecolic Acids; Platelet Aggregation; Protein C; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia; Warfarin

Enhanced adjunctive pharmacotherapy for percutaneous coronary revascularization is evolving. New modifications to the original antithrombotic, antiplatelet combination of heparin and aspirin have become part of standard practice. Platelet glycoprotein (GP) IIb/IIIa receptor inhibitors have been shown to decrease the incidence of death or nonfatal myocardial infarction at 30 days by approximately 50%. However, there are continuing concerns with this class of agents, including bleeding complications, cost, and the inability to identify which patients are most likely to benefit from their use. Bivalirudin, a direct thrombin inhibitor capable of inactivating clot-bound thrombin, has demonstrated enhanced short-term efficacy with a significantly decreased incidence of bleeding compared with heparin in patients with acute coronary syndromes. These findings provided a basis for a new, large-scale trial-Comparison of Abciximab Complications with Hirulog [and Back-Up Abciximab] Events Trial (CACHET)-which compares primary abciximab plus aspirin and heparin with aspirin plus intraprocedural bivalirudin and ad hoc abciximab. All patients who are candidates for stenting will receive clopidogrel before coronary intervention, and if stenting is performed, maintenance clopidogrel for 30 days. The trial aims to evaluate improved anticoagulation with bivalirudin and preprocedural oral antiplatelet protection and the use of ad hoc abciximab as a basis for a practical, acceptable antithrombotic, antiplatelet strategy to improve outcomes in percutaneous coronary revascularization.

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Aspirin; Cardiac Catheterization; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Research Design; Ticlopidine

Topics: Antithrombins; Arginine; Clinical Trials, Phase III as Topic; Fibrinolytic Agents; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides

Topics: Amino Acid Sequence; Animals; Antithrombins; Blood Platelets; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Molecular Sequence Data; Papio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Primates; Recombinant Proteins; Thrombin; Thrombosis

Beside the direct inhibition of thrombin and its regulatory functions, many of the newer antithrombin agents produce several additional effects, unrelated to their anticoagulant actions. Synthetic peptide inhibitors are capable of producing fibrinolytic compromise by virtue of their actions on fibrinolytic enzymes such as t-PA, plasmin, urokinase and protein Ca. In addition, the low molecular weight arginine-containing peptides are also known to produce hemodynamic and hemostatic deficits. The designs of the ongoing clinical trials are largely empirical because of the non-availability of valid pharmacologic and toxicologic data on thrombin inhibitors. In contrast to heparin, none of the thrombin inhibitors produce endogenous release of tissue factor pathway inhibitor (TFPI) in the experimental and clinical settings. These observations suggest that beside the direct inhibition of thrombin, these agents also produce multiple additional effects that can significantly contribute to their pharmacologic and toxicologic profile.

Topics: Amino Acid Sequence; Animals; Antithrombins; Aptamers, Nucleotide; Clinical Trials as Topic; Drug Design; Drug Evaluation, Preclinical; Fibrinolysis; Forecasting; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Lipoproteins; Molecular Sequence Data; Oligonucleotides; Peptide Fragments; Polynucleotides; Protease Inhibitors; Rabbits; Recombinant Proteins; Structure-Activity Relationship; Thrombin

Most of the clinical evaluation of the direct thrombin inhibitors has been in coronary artery disease. The recent clinical reports suggest that there is a narrower window of safety with recombinant hirudin than initially thought particularly when it is used in conjunction with thrombolytic agents and aspirin in acute myocardial infarction. The efficacy data, however, indicate that the direct thrombin inhibitors have great potential particularly in the initial management of patients with acute unstable angina and non-Q-wave infarction. There is much to learn regarding the mechanism of action, optimal dose, and optimal concomitant therapy in the use of direct thrombin inhibitors in the management of acute coronary ischaemia; and since hirudin and other direct thrombin inhibitors have so much potential in the management of acute coronary ischaemia, it is critical that dose-finding studies be performed to determine safe regimens of these agents to allow their evaluation in large-scale trials with important clinical outcomes. The direct thrombin inhibitors have also shown to have promise in the prevention of deep vein thrombosis in high-risk surgical patients. There is limited clinical data on the other novel anticoagulants which are currently being developed.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Aspirin; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Design; Drug Therapy, Combination; Enzyme Activation; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Lipoproteins; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Postoperative Complications; Protein C; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombolytic Therapy; Thrombophlebitis; Treatment Outcome

Topics: Animals; Cardiovascular System; Dogs; Female; Hemorrhage; Hirudins; Lipopolysaccharides; Mice; Rabbits; Rats; Recombinant Fusion Proteins; Respiratory System; Swine; Swine, Miniature; Thrombin

Topics: Animals; Blood Coagulation Tests; Blood Loss, Surgical; Factor VIIa; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Platelet Aggregation; Rabbits; Recombinant Fusion Proteins

Topics: Animals; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Leeches; Postoperative Complications; Recombinant Fusion Proteins; Thrombin; Thrombosis

Leeches have been in medical use for many years. Hirudin, the anticoagulant obtained from the medicinal leech has been purified, characterized and can now be produced by recombinant (r) technology. R-hirudin is a potent inhibitor of thrombin and is therefore a potentially valuable anticoagulant and antithrombotic drug. This article reviews the current status of r-hirudin in this role and compares the pharmacokinetics, mechanism of action and clinical efficacy of this agent with heparin. The methods available for laboratory assessment and clinical monitoring of r-hirudin and the possible ways of antagonizing its effects are also discussed. Finally, the potential clinical applications of r-hirudin are outlined, although further laboratory and clinical studies, together with a fall in the cost of this compound are required before r-hirudin can be more widely accepted as an anticoagulant and antithrombotic agent.

Topics: Amino Acid Sequence; Animals; Blood Coagulation; Blood Platelets; Drug Evaluation; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Molecular Sequence Data; Postoperative Complications; Recombinant Proteins; Thrombin; Thrombosis

Topics: Angioplasty, Balloon; Animals; Disseminated Intravascular Coagulation; Extracorporeal Circulation; Fibrinolytic Agents; Hemorrhage; Hirudin Therapy; Hirudins; Rabbits; Rats; Recombinant Fusion Proteins; Recurrence; Swine; Thrombolytic Therapy; Thrombosis

Recombinant hirudin (r-hirudin) is currently under development as an anticoagulant for use in surgery, therapeutic anticoagulation, disseminated intravascular coagulation and other pathologic states involving the generation of thrombin. Circulating levels of r-hirudin as an antithrombotic agent range from 2 to 20 micrograms/ml (0.1-1.0 mg/kg) as determined in an animal model of stasis thrombosis. In order to establish a relationship between the r-hirudin circulating level and bleeding, we utilized a rabbit ear blood loss model. r-Hirudin did not produce any loss of blood at dosages up to 20 micrograms/ml i.v. (1.0 mg/kg). When the circulating levels were maintained at 20 micrograms/ml for periods of up to 3 h, no increase in blood loss was observed. At 50 and 100 micrograms/ml initial circulating levels (2.5 and 5.0 mg/kg) a dose-dependent increase in the blood loss was observed which was equivalent to that observed with 1.25 and 2.5 mg/kg i.v. heparin. Such levels of r-hirudin are not expected in clinical usage. In contrast to heparin, the anticoagulant actions of r-hirudin were not neutralized by protamine sulfate, platelet factor 4, other polycationic agents and heparinase. In our studies, the blood loss induced by greater than 2.0 mg/kg i.v. dosages of r-hirudin in an animal model was neutralized by the administration of an activated prothrombin complex concentrate at 25 U/kg. In a similar experimental setting, r-factor VIIa was also partially effective. These studies suggest that r-hirudin anticoagulation may not require neutralization, since bleeding effects are not observed at effective antithrombotic dosages in individuals with normal hemostatic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antifibrinolytic Agents; Blood Loss, Surgical; Ear Diseases; Ear, External; Factor VIIa; Fibrinolytic Agents; Hemorrhage; Heparin; Heparin Antagonists; Heparin Lyase; Hirudins; Humans; Platelet Aggregation; Platelet Factor 4; Polysaccharide-Lyases; Protamines; Rabbits; Recombinant Proteins; Wounds, Stab

Topics: Animals; Blood Coagulation; Blood Coagulation Tests; Hemorrhage; Hirudin Therapy; Hirudins; Recombinant Proteins; Thrombin; Thrombosis

To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR).. CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact.. The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure.. Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding).. CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

Topics: Antithrombins; Coronary Artery Disease; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Transcatheter Aortic Valve Replacement; Treatment Outcome

Procedural myocardial injury (PMI), which is the most common complication of elective percutaneous coronary intervention (ePCI), is associated with future adverse cardiac events. In this randomized pilot trial, we assessed the effects of prolonged use of the anti-coagulant bivalirudin on PMI after ePCI. Patients undergoing ePCI were randomized into the following two groups: the bivalirudin use during operation group (BUDO, 0.75 mg/kg bolus plus 1.75 mg/kg/h) and the bivalirudin use during and after operation for 4 h (BUDAO, 0.75 mg/kg bolus plus 1.75 mg/kg/h). Blood samples were collected before and 24 h after ePCI (per 8 h). The primary outcome, PMI, was defined as an increase in post-ePCI cardiac troponin I (cTnI) levels of > 1 × 99th% upper reference limit (URL) when the pre-PCI cTnI was normal or a rise in cTnI of > 20% of the baseline value when it was above the 99th percentile URL, but it was stable or falling. Major PMI (MPMI) was defined as a post-ePCI cTnI increase of > 5 × 99th% URL. A total of 330 patients were included (n = 165 per group). The incidences of PMI and MPMI were not significantly higher in the BUDO group than in the BUDAO group (PMI: 115 [69.70%] vs. 102 [61.82%], P = 0.164; MPMI: 81 [49.09%] vs. 70 [42.42%], P = 0.269). However, the absolute change in cTnI levels (calculated as the peak value 24 h post-PCI minus the pre-PCI value) was notably larger in the BUDO group (0.13 [0.03, 1.95]) than in the BUDAO group (0.07 [0.01, 0.61]) (P = 0.045). Moreover, the incidence of bleeding events was similar between the two groups (BUDO: 0 [0.00%]; BUDAO: 2 [1.21%], P = 0.498). Prolonged infusion of bivalirudin for 4 h after ePCI reduces PMI severity without increasing the risk of bleeding.ClinicalTrials.gov.Number: NCT04120961, 09/10/2019.

Topics: Hemorrhage; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Treatment Outcome; Troponin I

Acute kidney injury (AKI) is not uncommon in patients undergoing transcatheter aortic valve replacement (TAVR).. We examined the incidence, predictors, and outcomes of AKI from the BRAVO 3 randomized trial.. The BRAVO-3 trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin vs. unfractionated heparin (UFH). The primary endpoint of the trial was Bleeding Academic Research Consortium (BARC) type ≥ 3b bleeding at 48 h. Total follow-up was to 30 days. AKI was adjudicated using the modified RIFLE (Valve Academic Research Consortium, VARC 1) criteria through 30-day follow-up, and in a sensitivity analysis AKI was assessed at 7 days (modified VARC-2 criteria). We examined the incidence, predictors, and 30-day outcomes associated with diagnosis of AKI. We also examined the effect of procedural anticoagulant (bivalirudin or unfractionated heparin, UFH) on AKI within 48 h after TAVR.. The trial population had a mean age of 82.3 ± 6.5 years including 48.8% women with mean EuroScore I 17.05 ± 10.3%. AKI occurred in 17.0% during 30-day follow-up and was associated with greater adjusted risk of 30-day death (13.0% vs. 3.5%, OR 5.84, 95% CI 2.62-12.99) and a trend for more BARC ≥ 3b bleeding (15.1% vs. 8.6%, OR 1.80, 95% CI 0.99-3.25). Predictors of 30-day AKI were baseline hemoglobin, body weight, and pre-existing coronary disease. AKI occurred in 10.7% at 7 days and was associated with significantly greater risk of 30-day death (OR 6.99, 95% CI 2.85-17.15). Independent predictors of AKI within 7 days included pre-existing coronary or cerebrovascular disease, chronic kidney disease (CKD), and transfusion which increased risk, whereas post-dilation was protective. The incidence of 48-h AKI was higher with bivalirudin compared to UFH in the intention to treat cohort (10.9% vs. 6.5%, p = 0.03), but not in the per-protocol assessment (10.7% vs. 7.1%, p = 0.08).. In the BRAVO 3 trial, AKI occurred in 17% at 30 days and in 10.7% at 7 days. AKI was associated with a significantly greater adjusted risk for 30-day death. Multivariate predictors of AKI at 30 days included baseline hemoglobin, body weight, and prior coronary artery disease, and predictors at 7 days included pre-existing vascular disease, CKD, transfusion, and valve post-dilation. Bivalirudin was associated with greater AKI within 48 h in the intention to treat but not in the per-protocol analysis.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Male; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Time Factors; Transcatheter Aortic Valve Replacement

Residual stent strut thrombosis after primary percutaneous coronary intervention (PCI), negatively affects myocardial perfusion, may increase stent thrombosis risk, and it is associated with neointima hyperplasia at follow-up.. To study the effectiveness of any bivalirudin infusion versus unfractionated heparin (UFH) infusion in reducing residual stent strut thrombosis in patients with ST-elevation myocardial infarction (STEMI).. Multi-vessel STEMI patients undergoing primary PCI and requiring staged intervention were selected among those randomly allocated to two different bivalirudin infusion regimens in the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) Treatment-Duration study. Those receiving heparin only were enrolled into a registry arm. Optical coherence tomography (OCT) of the infarct-related artery was performed at the end of primary PCI and 3-5 days thereafter during a staged intervention. The primary endpoint was the change in minimum flow area (ΔMinFA) defined as (stent area + incomplete stent apposition [ISA] area) - (intraluminal defect + tissue prolapsed area) between the index and staged PCI.. 123 patients in bivalirudin arm and 28 patients in the UFH arm were included. Mean stent area, percentage of malapposed struts, and mean percent thrombotic area were comparable after index or staged PCI. The ΔMinFA in the bivalirudin group was 0.25 versus 0.05 mm. The administration of bivalirudin after primary PCI significantly reduces residual stent strut thrombosis when compared to UFH. This observation should be considered hypothesis-generating since the heparin-treated patients were not randomly allocated.

Topics: Aged; Anticoagulants; Antithrombins; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Infusions, Parenteral; Italy; Male; Middle Aged; Neointima; Peptide Fragments; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; ST Elevation Myocardial Infarction; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention are at increased risk of both ischemic and bleeding complications. The optimal anticoagulation strategy in these patients is uncertain. Therefore, we compared bivalirudin to heparin monotherapy in a contemporary cohort of such patients.. A prespecified subgroup analysis of elderly patients with myocardial infarction (≥75 years) from the VALIDATE-SWEDEHEART trial (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) was performed. In the trial, patients were randomized to either bivalirudin or heparin monotherapy during percutaneous coronary intervention, with mandatory potent P2Y12 inhibition, routine radial artery access, and only bail-out glycoprotein IIb/IIIa inhibition. Kaplan-Meier event rates were assessed for the primary end point, consisting of a composite of all-cause death, myocardial reinfarction, or major bleeding, within 180 days.. The elderly (n=1592) had more than twice the risk of all events compared with younger patients (n=4406). Baseline and periprocedural characteristics were equal between bivalirudin (n=799) and heparin (n=793) treated patients ≥75 years. No differences were found in the elderly between bivalirudin and heparin monotherapy regarding the primary end point (180-day all-cause death, myocardial reinfarction, or major bleeding), the individual components of the primary end point, definite stent thrombosis, or stroke.. In this prespecified subgroup analysis of the VALIDATE-SWEDEHEART trial, elderly patients with myocardial infarction had a highly increased risk of all events. However, no difference in outcomes could be observed with an anticoagulation strategy with either bivalirudin or heparin as monotherapy in this patient group.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Recurrence; Registries; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Sweden; Time Factors; Treatment Outcome

The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use.. In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days.. Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

Topics: Aged; Anticoagulants; Antithrombins; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Stents; Sweden; Thrombosis; Ticagrelor

Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients.. This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days.. There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60-1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89-1.26),. In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.

Topics: Acute Disease; Administration, Intravenous; Aged; Anticoagulants; Antithrombins; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Registries; Risk Assessment; Sex Factors; ST Elevation Myocardial Infarction; Sweden

To assess the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in high-bleeding-risk elderly patients.. Bivalirudin reduces PCI-related bleeding; however, its efficacy and safety in patients with CTO, especially elderly patients with a high bleeding risk, remain unclear.. This single-center prospective randomized controlled trial assigned 123 high-bleeding-risk elderly patients with CTO to either the unfractionated heparin (UFH) group (n = 55) or the bivalirudin group (n = 68). The primary efficacy endpoint was the incidence of major adverse cardiac events (MACEs) during hospitalization and at the 6-month follow-up. The safety endpoint was bleeding or procedure (access)-related complications after PCI.. MACE incidence was 17.6% and 20.0% in the bivalirudin and UFH groups, respectively (P = 0.82). Bleeding Academic Research Consortium (BARC) type 1-2 bleeding events during hospitalization were comparable between the groups (UFH: 10.9% vs. bivalirudin: 8.8%, P = 0.77). No BARC type 3-5 bleeding events or severe procedure (access)-related complications (subcutaneous hematoma >5 cm) occurred in either group. At the 6-month follow-up, MACE incidence was comparable between the groups (UFH: 3.6% vs. bivalirudin: 1.5%, P = 0.59). The Kaplan-Meier analysis revealed that MACE-free survival rates were comparable between the groups (P = 0.43). One case of BARC type 3-5 bleeding (fatal intracranial hemorrhage) was observed in the UFH group at the 6-month follow-up.. Bivalirudin and UFH showed comparable efficacy and safety in elderly patients with a high bleeding risk, undergoing PCI for CTO lesions.

Topics: Age Factors; Aged; Anticoagulants; Antithrombins; China; Chronic Disease; Coronary Occlusion; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Progression-Free Survival; Prospective Studies; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors

Despite dual antiplatelet therapy patients undergoing percutaneous coronary intervention (PCI) continue to experience periprocedural ischemic events. In addition, all currently used antithrombotic drugs increase the bleeding risk. Thus, there is an unmet clinical need for antithrombotic strategies with improved efficacy and no increase in bleeding. Revacept is a novel, lesion-directed antithrombotic drug that does not interfere with the function of circulating platelets. This dimeric fusion protein of the extracellular domain of glycoprotein VI (the major platelet collagen receptor) and the human Fc-fragment inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. The randomized, double-blinded, phase II ISAR-PLASTER trial is based on extensive preclinical evaluation of Revacept and a favorable first-in-man trial. A total of 332 patients with stable coronary artery disease undergoing elective PCI will be randomized to either Revacept 160 mg, Revacept 80 mg, or placebo administered as single intravenous infusion directly before the intervention, on top of standard dual antiplatelet therapy and either heparin or bivalirudin, based on local practice and current guidelines. The primary endpoint is the composite of death or myocardial injury (defined as increase in high sensitivity troponin T ≥ 5 times the upper limit of normal) at 48 hours. The safety endpoint is bleeding of class 2 or higher according to the Bleeding Academic Research Consortium at 30 days. This phase II randomized, double blind trial will assess for the first time the efficacy and safety of Revacept-a lesion-directed inhibitor of platelet adhesion-in patients undergoing elective PCI.

Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; Coronary Artery Disease; Double-Blind Method; Dual Anti-Platelet Therapy; Elective Surgical Procedures; Female; Fibrinolytic Agents; Germany; Glycoproteins; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fc Fragments; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Placebos; Platelet Aggregation; Recombinant Proteins; Survival Analysis; Young Adult

In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with acute coronary syndrome undergoing invasive management. We assessed whether the access site had an impact on the primary endpoint of death, myocardial infarction or major bleeding at 180 days and whether it interacted with bivalirudin/unfractionated heparin.. Transradial access was associated with lower risk of death, myocardial infarction or major bleeding at 180 days. Bivalirudin was not associated with less bleeding, irrespective of access site.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Radial Artery; Recombinant Proteins; Registries; ST Elevation Myocardial Infarction; Treatment Outcome

Bivalirudin has been reported to be an alternative to unfractionated heparin (UFH) for anticoagulation during percutaneous coronary intervention (PCI) and associated with less bleeding risk. However, the feasibility of bivalirudin during PCI of chronic total occlusion lesions (CTO) remains unknown.. To evaluate the efficacy and safety of bivalirudin versus UFH in CTO PCI.. In this prospective and randomized controlled trial in single center, CTO patients with high bleeding risk were randomized to treatment with bivalirudin (bolus 0.75 mg/kg followed by infusion of 1.75, extra bolus 0.3 mg/kg before stenting) or UFH (100 IU/kg). The primary efficacy end point was the incidence of major adverse cardiac events (MACEs, composite of all-cause mortality, cardiac death, stent thrombosis, periprocedural myocardial infarction, or additional unplanned target lesion revascularization, or any other post-PCI ischemic event) in-hospital, and at 1-year follow-up. The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI.. A total of 84 high bleeding risk patients undergoing PCI for CTO lesions were enrolled. The baseline characteristics were similar in both treatment arms. In hospital MACEs rates were 21.4% in the bivalirudin group and 14.3% in the UFH group (P = 0.393). During 1-year's follow-up, end points did not significantly differ between the groups either. Occurrence of the major bleeding events were 4.8% in the bivalirudin group and 9.5% in the UFH group (P = 0.676). No entry-site complication was observed.. In CTO patients at high risk for bleeding undergoing PCI, our data indicates that bivalirudin appears to be at least comparable in efficacy and safety to UFH. A larger clinical trial should be designed to further elucidate its efficacy and safety.

Topics: Aged; Anticoagulants; Antithrombins; China; Chronic Disease; Coronary Occlusion; Coronary Thrombosis; Feasibility Studies; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Pilot Projects; Prospective Studies; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

To compare bleeding and clinical events of patients with stable angina or silent ischemia undergoing percutaneous coronary intervention (PCI) treated with unfractionated heparin (UFH) or bivalirudin.. Few direct comparisons between UFH monotherapy versus bivalirudin exist for patients with stable ischemic heart disease undergoing PCI.. A prospective, investigator-initiated, single-center, single-blinded, randomized trial of UFH versus bivalirudin was conducted. The primary endpoint was all bleeding (major and minor) from index-hospitalization to 30 days post discharge. Secondary endpoints included major adverse cerebral and cardiovascular events (MACCE) and net adverse clinical events (NACE).. Two-hundred-sixty patients were randomized for treatment with either UFH (n = 123) (47%) or bivalirudin (n = 137) (53%) There were no significant differences in baseline clinical and angiographic characteristics between the two groups. Primary endpoint was similar in both groups (10.9% with bivalirudin vs 7.3% with UFH [P = 0.31]). Major bleeding rates were 5.8% and 2.4%, respectively (P = 0.17). There was a higher MACCE (3.5% vs 0%, P = 0.03) and NACE (8.8% vs 2.4%, P = 0.03) rate with bivalirudin compared to UFH, respectively. Bivalirudin had increased odds of NACE (OR = 3.65, 95% CI: 1.00-13.3.6). Death and stent thrombosis rates were low and similar in both groups. Radial access was associated with fewer bleeding events compared to femoral access but not statistically significant (P = 0.29).. Among patients with stable angina or silent ischemia, there was no difference between UFH and bivalirudin in bleeding rates up to 30-days post-PCI. MACCE and NACE were higher among the bivalirudin group. Radial access was associated with a numerically lower rate of bleeding compared with femoral access.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Drug Monitoring; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Thrombosis; Treatment Outcome

Contrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs).. This study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management.. In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding).. Among 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site-related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site.. In patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627).

Topics: Acute Coronary Syndrome; Aged; Coronary Artery Bypass; Electrocardiography; Female; Hematologic Agents; Hemorrhage; Heparin; Hirudins; Humans; Intraoperative Care; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Treatment Outcome

The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme.. MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70-100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50-70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627.. Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80-1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78-0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83-1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81-1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84-1·16; p=0·90).. In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management.. Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Coronary Angiography; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Perioperative Care; Platelet Glycoprotein GPIIb-IIIa Complex; Prosthesis Failure; Radial Artery; Recombinant Proteins; Stents; Stroke

The randomized, LEADERS FREE trial showed superior safety and efficacy of a polymer-free DCS vs. a bare metal stent in high-bleeding risk patients with only one month dual antiplatelet treatment. We report characteristics and outcomes of the pre-specified group of elderly patients (aged ≥75).. Age >75 was one of the trial's inclusion criteria. The main additional criteria were: need for oral anticoagulants, recent bleeding, anemia, chronic renal failure and cancer. All patients received 1month DAPT only. Both primary endpoints (efficacy: clinically driven TLR and safety: composite of cardiac death, MI and stent thrombosis) as well as bleeding were recorded up to 390days.. 1564 elderly patients (63.4% of the population) were enrolled with a mean of 2 inclusion criteria/patient. The primary safety endpoint was reached less frequently in DCS than BMS patients (10.7 vs. 14.3%, p=0.03), as was the primary efficacy endpoint (5.8 vs. 10.8% p=0.0003). Major bleeding rates were high and similar in both groups (7.3 vs. 8.2%, p=0.55). For the 562 (23.4%) patients with age as sole entry criterion, trends were similar for DCS and BMS patients respectively: safety endpoint (7.3%vs.11.4% p=0.10) and Cd TLR (4.7 vs. 13.2% p=0.0003), but for both groups, major bleeding occurred less frequently than for elderly patients with more comorbid conditions (3.6%vs. 2.8%).. Compared to a BMS, use of a DCS together with a short one-month DAPT course was associated with significant safety and efficacy benefits for the elderly patients enrolled in LEADERS FREE.

Topics: Age Factors; Aged; Aged, 80 and over; Antithrombins; Double-Blind Method; Drug-Eluting Stents; Female; Hemorrhage; Hirudins; Humans; Male; Metals; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Sirolimus; Stents; Treatment Outcome

A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76).. Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).

Topics: Aged; Anticoagulants; Combined Modality Therapy; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Recombinant Proteins

To explore the efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access.. Bivalirudin reduces bleeding risks over heparin in patients undergoing PCI. However, bleeding advantages of bivalirudin in patients undergoing transradial intervention is uncertain.. In the BRIGHT trial, 1,723 patients underwent emergency PCI via radial access, with 576 patients in the bivalirudin arm, 576 in the heparin arm and 571 in the heparin plus tirofiban arm. The primary outcome was 30-day net adverse clinical event (NACE), defined as a composite of major cardiac and cerebral events or any bleeding.. 30-day NACE occurred in 5.7% with bivalirudin, 7.8% with heparin alone (vs. bivalirudin, P = 0.159), and 10.3% with heparin plus tifofiban (vs. bivalirudin, P = 0.004). The 30-day bleeding rate was 0.9% for bivalirudin, 2.3% for heparin (vs. bivalirudin, P = 0.057), and 5.8% for heparin plus tirofiban (vs. bivalirudin, P < 0.001). Major cardiac and cerebral events (4.9 vs. 5.7 vs. 4.6%, P = 0.899), stent thrombosis (0.5 vs. 0.5 vs. 0.7%, P = 0.899) and acquired thrombocytopenia (0.2 vs. 0.5 vs. 0.9%, P = 0.257) at 30 days were similar among three arms. The interaction test for PCI access and randomized treatment showed no significance on all bleeding (P > 0.05).. The bleeding benefit of bivalirudin was independent of artery access. Bivalirudin lead to statistical reduction on bleeding risks in comparison to heparin plus tirofiban, and only small numerical difference in comparison to heparin, with comparable risks of ischemic events and stent thrombosis in patients with acute myocardial infarction (AMI) undergoing emergency transradial PCI. © 2016 Wiley Periodicals, Inc.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Cardiac Catheterization; China; Emergencies; Female; Hemorrhage; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Radial Artery; Recombinant Proteins; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Time Factors; Tirofiban; Treatment Outcome; Tyrosine; Warfarin; Young Adult

To compare bivalirudin to heparin during non-primary percutaneous coronary intervention (PCI).. The optimal anticoagulant to support PCI remains uncertain.. We performed a propensity score-based analysis comparing clinical outcomes of patients receiving heparin to those receiving bivalirudin during non-primary PCI.. Of 18,867 patients in the Cardiovascular Patient Outcomes Research Team Non-Primary PCI (CPORT-E) trial, we selected 7,913 patients undergoing non-staged PCI of whom 57.3% received heparin and 42.7% received bivalirudin. In-hospital myocardial infarction occurred in 4.4% of patients receiving bivalirudin and 3.0% of patients receiving heparin (relative risk [RR] 1.5, 95% confidence interval [CI] 1.1-2.1, P = 0.022); this difference persisted at 6 weeks (5.0% vs. 3.6%, RR 1.4, 95% CI 1.0-1.8, P = 0.041). There was no difference in all-cause mortality either in-hospital (0.2% vs. 0.1% for heparin vs. bivalirudin, P = 0.887) or at 6 weeks (0.5% vs. 0.7%, P = 0.567). In-hospital bleeding requiring transfusion occurred in 0.9% of patients receiving bivalirudin and 1.9% of patients receiving heparin (RR 0.4, 95% CI 0.3-0.7, P <0.001), but there was no difference at 6 weeks (2.7% for heparin vs. 1.9% for bivalirudin, RR 0.7, 95% CI 0.5-1.0, P = 0.062).. In patients undergoing non-primary PCI at hospitals without on-site cardiac surgery, bivalirudin was associated with a decreased risk of in-hospital bleeding requiring transfusion and an increased risk of in-hospital MI compared to heparin. © 2017 Wiley Periodicals, Inc.

Topics: Aged; Anticoagulants; Antithrombins; Blood Transfusion; Coronary Disease; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Propensity Score; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

To evaluate the impact of antithrombotic regimens during the medical phase of treatment among 13,819 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) treated with an early invasive strategy in the acute catheterization and urgent intervention triage strategy (ACUITY) trial.. Endpoints included composite major adverse cardiac events (MACE), major bleeding, and net adverse clinical events (NACE; MACE or major bleeding). The median (interquartile range) duration of antithrombin use in the medical only treatment phase was 6.5 (1.8-22.5) hours. MACE, major bleeding, and NACE during the medical only phase occurred in 63 (0.5%), 117 (0.9%), and 178 (1.3%) patients, respectively. MACE rates in the medical-treatment-only phase were not significantly different between the four randomized medical regimens used (heparin alone, bivalirudin alone, heparin plus a glycoprotein IIb/IIIa inhibitor [GPI], and bivalirudin plus GPI) (Ptrend  = 0.65). The lowest rates of major bleeding and NACE during the medical treatment phase occurred in patients treated with bivalirudin alone (Ptrend  = 0.0006 and Ptrend  = 0.0004, respectively).. In patients with NSTE-ACS undergoing an early invasive strategy, treatment with bivalirudin alone significantly reduced major bleeding and improved net clinical outcomes during the upstream medical management phase with comparable rates of MACE. © 2015 Wiley Periodicals, Inc.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Coronary Artery Bypass; Drug Therapy, Combination; Enoxaparin; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding.. We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions.. 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002).. The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin.. Regado Biosciences Inc.

Topics: Aged; Anticoagulants; Aptamers, Nucleotide; Coagulants; Drug Hypersensitivity; Early Termination of Clinical Trials; Europe; Factor IXa; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; North America; Oligonucleotides; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

Women have higher bleeding complication and mortality rates after percutaneous coronary interventions (PCI). The contribution of female gender to bleeding and mortality is poorly understood. We evaluated the effect of gender and bleeding on outcomes of patients treated with bivalirudin during PCI by performing a patient-level pooled analysis of 3 randomized controlled trials (the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events, Acute Catheterization and Urgent Intervention Triage strategY, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) comparing bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor (GPI) treatment in patients undergoing PCI. Of 14,784 patients, 7,413 patients received bivalirudin (1,870 women) and 7,371 patients received heparin + GPI (1,910 women). Women had significantly higher 30-day non-coronary artery bypass grafting (CABG)-related major bleeding rates (7.6% vs 3.8%, p <0.0001). After multivariate adjustment, female gender increased the hazard of major bleeding by 80% (hazard ratio 1.80, 95% confidence interval 1.52 to 2.11, p <0.001). Furthermore, women had a higher 1-year mortality rate (3.7% vs 2.7%, p = 0.002) than men; 30-day major bleeding was the strongest independent predictor of 1-year mortality in women (hazard ratio 2.48, 95% confidence interval 1.57 to 3.91, p = 0.001). Bivalirudin therapy in women reduced 30-day non-CABG-related major bleeding (5.6% vs 9.7%, p <0.0001) and 1-year mortality (2.9% vs 4.4%, p = 0.02) compared to standard therapy. In conclusion, in this cohort of patients treated for acute coronary syndrome and ST-segment elevation myocardial infarction, women have a near 2-fold increase in bleeding complications compared to men after PCI. Bleeding complications rather than gender is the strongest independent predictor of 1-year mortality in patients undergoing PCI. Furthermore, we observed a more pronounced clinical benefit in women treated with bivalirudin including a 44% reduction in major bleeding and a significant reduction in mortality rates at 1 year.

Topics: Aged; Antithrombins; Argentina; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk Factors; Survival Rate; Time Factors; United Kingdom; United States

Being female is an independent predictor of adverse events during percutaneous coronary interventions (PCI).. To evaluate the safety and efficiency of bivalirudin during emergency PCI in female patients with acute myocardial infarction (AMI).. The present study was a subgroup analysis of the randomized Bivalirudin in Acute Myocardial Infarction vs. Heparin and GPI plus Heparin (BRIGHT) trial. A total of 392 female patients enrolled in the BRIGHT trial were assigned to receive bivalirudin with post-procedure dose infusion (n = 127) or heparin with or without tirofiban (n = 265). The primary efficiency endpoint was 30-day net adverse clinical events (NACEs). The secondary efficiency endpoints were 30-day major cardiac and cerebral events (MACCEs) and bleeding events defined according to Bleeding Academic Research Consortium (BARC) definitions.. For female patients, bivalirudin treatment was associated with significantly lower incidences of 30-day NACEs (6.3% vs. 21.5%, P < 0.001), any bleeding (2.4% vs. 12.8%, P = 0.001) and BARC 2-5 type bleeding (1.6% vs. 7.2%, P = 0.021) compared with the control regimen. The incidence of MACCEs (3.4% vs. 9.4%, P = 0.055) and stent thrombosis (0% vs. 1.1%, P = 0.229) were comparable between the two groups. Multivariate analysis showed that bivalirudin (OR: 0.245, 95% CI: 0.113-0.532, P < 0.001), transradial access (OR: 0.119, 95% CI: 0.067-0.211, P < 0.001), and statin (OR: 0.254, 95% CI: 0.08-0.807, P = 0.02) were independent protective factors for 30-day NACEs in female patients.. The use of bivalirudin during emergency PCI for AMI in female patients significantly reduced the bleeding risk with anticoagulation effects compared with heparin with or without tirofiban.

Topics: Aged; Anticoagulants; Antithrombins; Chi-Square Distribution; Coronary Thrombosis; Drug Therapy, Combination; Drug-Eluting Stents; Emergency Treatment; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Protective Factors; Recombinant Proteins; Risk Assessment; Risk Factors; Sex Factors; Time Factors; Tirofiban; Treatment Outcome; Tyrosine

To assess the relationship of femoral vascular closure device (VCD) use to bleeding and ischemic events in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) via different anticoagulation strategies.. It is unknown whether femoral VCD reduce major bleeding after primary PCI for STEMI using bivalirudin anticoagulation.. We compared VCD-treated patients with propensity-matched controls in the HORIZONS-AMI trial with respect to net adverse clinical events (NACE), defined as the composite of major bleeding unrelated to coronary artery bypass graft surgery (CABG) and major adverse cardiac events (comprised of death, reinfarction, ischemia-driven target vessel revascularization, and stroke), at 30 days and 1 year.. Among 3,602 patients enrolled in HORIZONS-AMI, 2,948 underwent primary PCI via femoral arterial access and 896 (30%) received VCDs, of whom 642 were included in our model along with 642 propensity-matched controls. At 30 days, VCD-treated patients had significantly less NACE (6.7% vs. 10.8%, HR: 0.61, 95% CI: 0.42-0.89, P = 0.009), driven by a lower rate of non-CABG related major bleeding (5.0% vs. 8.1%, HR: 0.61, 95% CI: 0.39-0.94, P = 0.02). Bleeding reduction was maintained at one year and consistent in magnitude regardless of randomization to bivalirudin or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (P for interaction = 0.84).. In patients undergoing transfemoral primary PCI for STEMI, VCD use was associated with significantly lower non-CABG major bleeding irrespective of anticoagulation strategy.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Chi-Square Distribution; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Propensity Score; Punctures; Recombinant Proteins; Recurrence; Risk Factors; Time Factors; Treatment Outcome; Vascular Closure Devices

Early initiation of dual antiplatelet therapy (DAPT) is guideline-recommended. MULTIPRAC was conducted to gain insights into the use patterns and outcomes of pre-hospital DAPT initiation with prasugrel or clopidogrel.. MULTIPRAC is a multinational, multicentre, prospective registry enrolling 2053 ST-segment elevation myocardial infarction (STEMI) patients. Patients were grouped according to adherence to the initially prescribed thienopyridine. Pre-hospital use of prasugrel increased from 12.5% to 67.1% at study end. Prasugrel compared to clopidogrel-initiated patients more often adhered to the medication through discharge (87% vs. 38%) whereas 49% of the clopidogrel-initiated patients were switched to prasugrel. Patients who continued on clopidogrel were substantially older. In-hospital mortality was 0.5%, early stent thrombosis 0.1%. The major adverse cardiac events (MACE) rate was 1.6% in prasugrel-treated vs. 2.3% in clopidogrel-treated patients (adjusted OR 0.749, 95% CI [0.285-1.968]). Non-coronary artery bypass graft (non-CABG) bleeding occurred in 4.1% of prasugrel-treated vs. 6.1% of clopidogrel-treated patients (adjusted OR 0.686 [0.349-1.349]). Pre-percutaneous coronary intervention (PCI) TIMI flow 2-3 was seen in 38.7% treated with prasugrel vs. 35.6% with clopidogrel (adjusted OR 1.170 [0.863-1.585]). Post PCI ST-segment resolution ⩾50%, was 71.6% with prasugrel vs. 65.0% with clopidogrel (adjusted OR 1.543 [1.138-2.093], p=0.0052).. MULTIPRAC demonstrated a steady increase in prasugrel use over time without an increase in bleeding rates compared to clopidogrel. ST resolution was more pronounced with prasugrel. Switching between antiplatelet drugs occurs frequently. The low rates of MACE, in-hospital mortality and bleeding, suggests that pre-hospital loading with thienopyridines is confined to low-risk patients. These results emphasize the need for more randomized pre-hospital studies and should be seen in the context of upcoming randomized trials involving pre-hospital antiplatelet therapies.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Clopidogrel; Drug Therapy, Combination; Europe; Female; Hemorrhage; Hirudins; Humans; Internationality; Male; Medication Adherence; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Recombinant Proteins; Ticlopidine; Treatment Outcome

Target vessel revascularization (TVR) may compromise the benefits of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction (STEMI) We set out to identify the predictors and examine the impact of TVR after STEMI in patients receiving a coronary stent.. In HORIZONS-AMI, 3,602 patients with STEMI were randomized to bivalirudin versus heparin and a glycoprotein IIb/IIIa inhibitor. Stents were implanted in 3,202 patients (2,982 were randomized to bare-metal stents versus paclitaxel-eluting stents, and 220 received nonrandomized stents).. Target vessel revascularization occurred in 219 patients (6.9%) at 1 year and in 437 patients (14.4%) at 3 years. Target vessel revascularization was ischemia-driven in 418 cases (95.7%). Target vessel revascularization was due to restenosis in 219 patients (50.1%), definite stent thrombosis in 124 (28.4%), and disease progression in 94 (21.5%). Independent predictors of TVR were more extensive coronary artery disease, smaller vessel size, longer lesion length and the number of stents implanted, post-percutaneous coronary intervention diameter stenosis, symptom onset to balloon time, treatment with bare-metal stents rather than paclitaxel-eluting stents, and scheduled angiographic follow-up. Target vessel revascularization was an independent predictor of subsequent myocardial infarction (hazard ratio [HR] 5.25, P < .0001), ST (HR 5.98, P < .0001), and major bleeding (HR 5.25, P < .0001) but not mortality (HR 0.88, P = .61).. In HORIZONS-AMI, TVR within 3 years after stent implantation was performed in ~1 of every 7 patients and was associated with more extensive coronary disease, more complex procedures, and bare metal stents. Target vessel revascularization was often due to stent thrombosis and disease progression as well as restenosis and was strongly associated with adverse outcomes but not mortality.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Antithrombins; Coronary Angiography; Coronary Restenosis; Disease Progression; Drug-Eluting Stents; Electrocardiography; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Paclitaxel; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Prognosis; Recombinant Proteins; Reoperation

This study sought to assess the safety and the efficacy of bivalirudin compared with unfractionated heparin (UFH) alone in the subset of patients at increased risk of bleeding undergoing transfemoral elective percutaneous coronary intervention (PCI).. Bivalirudin, a synthetic direct thrombin inhibitor, determines a significant decrease of in-hospital bleeding following PCI.. This is a single-center, investigator-initiated, randomized, double-blind, controlled trial. Consecutive biomarker-negative patients at increased bleeding risk undergoing PCI through the femoral approach were randomized to UFH (UFH group; n = 419) or bivalirudin (bivalirudin group; n = 418). The primary endpoint was the rate of in-hospital major bleeding.. The primary endpoint occurred in 11 patients (2.6%) in the UFH group versus 14 patients (3.3%) in the bivalirudin group (odds ratio: 0.78; 95% confidence interval: 0.35 to 1.72; p = 0.54). Distribution of access-site and non-access-site bleeding was 18% and 82% in the UFH group versus 50% and 50% in the bivalirudin group (p = 0.10).. The results of this randomized study, carried out at a single institution, suggest that there is no difference in major bleeding rate between bivalirudin and UFH in increased-risk patients undergoing transfemoral PCI. (Novel Approaches in Preventing and Limiting Events III Trial: Bivalirudin in High-Risk Bleeding Patients [NAPLES III]; NCT01465503).

Topics: Aged; Aged, 80 and over; Coronary Artery Disease; Double-Blind Method; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Italy; Male; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Punctures; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The aim of this study was to examine the efficacy and bleeding outcomes of cangrelor in patients in the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI]) who underwent percutaneous coronary intervention with bivalirudin.. Cangrelor is a potent intravenous P2Y12 inhibitor with rapid onset and offset. In the CHAMPION PHOENIX, cangrelor compared with clopidogrel significantly reduced 48-h ischemic events including stent thrombosis, without increasing major bleeding. Bivalirudin has demonstrated ischemic outcomes similar to those with heparin plus glycoprotein IIb/IIIa inhibition, with reduced bleeding but increased early stent thrombosis.. In the modified intent-to-treat population, 2,059 patients (18.8%) received bivalirudin, with 1,014 patients in the cangrelor treatment arm and 1,045 in the clopidogrel treatment arm.. At 48 h, the primary endpoint of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis was lower with cangrelor versus clopidogrel (48 [4.7%] vs. 70 [6.7%]; odds ratio [OR]: 0.68, p = 0.047). Death was similar in both arms (2 [0.2%] vs. 2 [0.2%]). Myocardial infarction was reduced by cangrelor (37 [3.6%] vs. 59 [5.6%]; OR: 0.63, p = 0.03), as was death/myocardial infarction (39 [3.8%] vs. 61 [5.8%]; OR: 0.65, p = 0.04). Cangrelor was associated with a nonsignificant trend toward less stent thrombosis (7 [0.7%] vs. 15 [1.4%]; OR: 0.48, p = 0.10), which was evident within 2 h after percutaneous coronary intervention (p = 0.057). GUSTO (Global Use of Strategies to Open Occluded Arteries) severe bleeding was similar in both arms (2 of 1,021 [0.2%] vs. 2 of 1,055 [0.2%]) as were other bleeding definitions and transfusions. Efficacy and safety results were consistent in patients with stable angina, non-ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction (p for interaction: 0.62 and 0.29).. Cangrelor may offer an attractive benefit risk profile when used in combination with bivalirudin.

Topics: Adenosine Monophosphate; Aged; Anticoagulants; Chi-Square Distribution; Clopidogrel; Coronary Artery Disease; Coronary Thrombosis; Double-Blind Method; Female; Hemorrhage; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Factors; Stents; Ticlopidine; Time Factors; Treatment Outcome

The safety and efficacy of bivalirudin compared with heparin with or without glycoprotein IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are uncertain.. To determine if bivalirudin is superior to heparin alone and to heparin plus tirofiban during primary PCI.. Multicenter, open-label trial involving 2194 patients with AMI undergoing primary PCI at 82 centers in China between August 2012 and June 2013.. Patients were randomly assigned to receive bivalirudin with a post-PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a post-PCI infusion (n = 730). Among patients treated with bivalirudin, a postprocedure 1.75 mg/kg/h infusion was administered for a median of 180 minutes (IQR, 148-240 minutes).. The primary end point was 30-day net adverse clinical events, a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or bleeding. Additional prespecified safety end points included the rates of acquired thrombocytopenia at 30 days, and stent thrombosis at 30 days and 1 year.. Net adverse clinical events at 30 days occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67; 95% CI, 0.50-0.90; difference, -4.3%, 95% CI, -7.5% to -1.1%; P = .008); and 124 patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin vs heparin plus tirofiban, 0.52; 95% CI, 0.39-0.69; difference, -8.1%, 95% CI, -11.6% to -4.7%; P < .001). The 30-day bleeding rate was 4.1% for bivalirudin, 7.5% for heparin, and 12.3% for heparin plus tirofiban (P < .001). There were no statistically significant differences between treatments in the 30-day rates of major adverse cardiac or cerebral events (5.0% for bivalirudin, 5.8% for heparin, and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6% vs 0.9% vs 0.7%, respectively, P = .77), acquired thrombocytopenia (0.1% vs 0.7% vs 1.1%; P = .07), or in acute (<24-hour) stent thrombosis (0.3% in each group). At the 1-year follow-up, the results remained similar.. Among patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3-hour postprocedure PCI-dose infusion resulted in a decrease in net adverse clinical events compared with both heparin alone and heparin plus tirofiban. This finding was primarily due to a reduction in bleeding events with bivalirudin, without significant differences in major adverse cardiac or cerebral events or stent thrombosis.. clinicaltrials.gov Identifier: NCT01696110.

Topics: Aged; Antithrombins; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Tirofiban; Tyrosine

Acute kidney injury (AKI) is an important complication of both diagnostic cardiac catheterization and percutaneous coronary intervention (PCI). A large body of evidence supports that AKI is related to volume of contrast used. Despite several measures are available to reduce the impact of contrast media on AKI, its incidence remains significant as other mechanisms of renal damage are involved. A new paradigm is established according to which bleeding prevention is at least as important as preventing recurrent ischemic events in the management of patients with acute coronary syndromes (ACS) undergoing an invasive approach. Periprocedural bleeding, which is consistently reduced by radial approach, is emerging as a risk factor for the development of AKI. Therefore, the role of vascular access as a measure to prevent AKI needs to be systematically assessed in randomized studies. To date, no prospective comparison on renal outcomes has been carried out in randomized trials between radial and femoral approach. The Minimizing Adverse hemorrhagic events by TRansradial access site and systemic Implementation of AngioX (MATRIX) trial (ClinicalTrials.gov identifier: NCT01433627) has been designed to test whether to minimize bleeding events by using radial access and bivalirudin, across the whole spectrum of patients with ACS undergoing PCI, will result in improved outcomes with respect to both ischemic and bleeding complications. The AKI-MATRIX sub-study will provide a unique opportunity to assess whether the advantages of radial approach may even contribute to the reduction of the risk of AKI in patients with ACS.

Topics: Acute Coronary Syndrome; Acute Kidney Injury; Antithrombins; Catheterization, Peripheral; Clinical Protocols; Contrast Media; Coronary Angiography; Hemorrhage; Hirudins; Humans; Incidence; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Punctures; Radial Artery; Recombinant Proteins; Research Design; Risk Factors; Time Factors; Treatment Outcome

In European Ambulance Acute Coronary Syndrome Angiography (EUROMAX), bivalirudin improved 30-day clinical outcomes with reduced major bleeding compared with heparins plus optional glycoprotein IIb/IIIa inhibitors. We assessed whether choice of access site (radial or femoral) had an impact on 30-day outcomes and whether it interacted with the benefit of bivalirudin.. In EUROMAX, choice of arterial access was left to operator discretion. Overall, 47% of patients underwent radial and 53% femoral access. Baseline risk was higher in the femoral access group. Unadjusted proportions for the primary outcome (death or noncoronary artery bypass graft protocol major bleeding at 30 days) were lower with radial access, however, without differences in major or major plus minor bleeding proportions. After multivariable adjustment, ischemic outcomes were no longer different between access site groups, except for a lower risk of stroke in radial patients. Bivalirudin was associated with lower proportions of the primary outcome in both the radial (odds ratio, 0.58; 95% CI, 0.33-1.03; P=0.058) and the femoral groups (odds ratio, 0.59; 95% CI, 0.37-0.93; P=0.022; interaction P=0.97). Bleeding was significantly lower in the bivalirudin group both in the radial- and femoral-treated patients but no significant difference was observed in ischemic outcomes. In multivariable analysis, bivalirudin emerged as the only independent predictor of reduced major bleeding (odds ratio, 0.45; 95% CI, 0.27-0.74; P=0.002).. In this prespecified analysis from EUROMAX, radial access was preferred in lower risk patients and did not improve clinical outcomes. Bivalirudin was associated with less bleeding irrespective of access site.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01087723.

Topics: Aged; Antithrombins; Female; Femoral Artery; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Radial Artery; Recombinant Proteins; Treatment Outcome

Direct thrombin inhibitors offer potential advantages over unfractionated heparin but have been poorly studied in children.. To determine appropriate dosing of bivalirudin in children and adolescents and the relationship between activated partial thromboplastin time (APTT) and plasma bivalirudin concentration.. The UNBLOCK (UtilizatioN of BivaLirudin On Clots in Kids) study was an open-label, single-arm, dose-finding, pharmacokinetic, safety and efficacy study of bivalirudin for the acute treatment of deep vein thrombosis (DVT) in children aged 6 months to 18 years. Drug initiation consisted of a bolus dose (0.125 mg kg(-1) ) followed by continuous infusion (0.125 mg kg h(-1) ). Dose adjustments were based on the APTT, targeting a range of 1.5-2.5 times each patient's baseline APTT. Safety was assessed by specific bleeding endpoints and efficacy by repeat imaging at 48-72 h and 25-35 days.. Eighteen patients completed the study. Following the bolus dose and the initial infusion rate, most patients' APTT values were within the target range. The infusion rate bivalirudin correlated more closely with drug concentration than the APTT. At 48-72 h, nine (50%) patients had complete or partial thrombus resolution, increasing to 16 (89%) at 25-35 days. No major and one minor bleeding event occurred.. Bivalirudin demonstrated reassuring safety and noteworthy efficacy in terms of early clot resolution in children and adolescents with DVT. Although a widely available and familiar monitoring tool, the APTT correlates poorly with plasma bivalirudin concentration, possibly limiting its utility in managing pediatric patients receiving bivalirudin for DVT.

Topics: Adolescent; Age Factors; Antithrombins; Biomarkers; Child; Child, Preschool; Critical Illness; Dose-Response Relationship, Drug; Drug Monitoring; Female; Hemorrhage; Hirudins; Humans; Infant; Infusions, Intravenous; Injections, Intravenous; Male; Partial Thromboplastin Time; Peptide Fragments; Prospective Studies; Recombinant Proteins; Venous Thrombosis

Early invasive management and the use of combined antithrombotic therapies have decreased the risk of recurrent ischaemia in patients with acute coronary syndrome (ACS) but have also increased the bleeding risk. Transradial intervention (TRI) and bivalirudin infusion compared to transfemoral intervention (TFI) or unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decrease bleeding complications in patients with ACS. To what extent, a bleeding preventive strategy incorporating at least one of these two treatment options translates into improved outcomes is a matter of debate. The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX study is a large-scale, multicenter, prospective, open-label trial, conducted at approximately 100 sites in Europe aiming to primarily assess whether TRI and bivalirudin infusion, as compared to TFI and UFH plus provisional GPI, decrease the 30-day incidence of death, myocardial infarction or stroke across the whole spectrum of ACS patients.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Clinical Protocols; Drug Therapy, Combination; Europe; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Punctures; Radial Artery; Recombinant Proteins; Research Design; Risk Factors; Time Factors; Treatment Outcome

Radiation absorbed by interventional cardiologists is a frequently under-evaluated important issue. Aim is to compare radiation dose absorbed by interventional cardiologists during percutaneous coronary procedures for acute coronary syndromes comparing transradial and transfemoral access.. The randomized multicentre MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial has been designed to compare the clinical outcome of patients with acute coronary syndromes treated invasively according to the access site (transfemoral vs. transradial) and to the anticoagulant therapy (bivalirudin vs. heparin). Selected experienced interventional cardiologists involved in this study have been equipped with dedicated thermoluminescent dosimeters to evaluate the radiation dose absorbed during transfemoral or right transradial or left transradial access. For each access we evaluate the radiation dose absorbed at wrist, at thorax and at eye level. Consequently the operator is equipped with three sets (transfemoral, right transradial or left transradial access) of three different dosimeters (wrist, thorax and eye dosimeter). Primary end-point of the study is the procedural radiation dose absorbed by operators at thorax. An important secondary end-point is the procedural radiation dose absorbed by operators comparing the right or left radial approach. Patient randomization is performed according to the MATRIX protocol for the femoral or radial approach. A further randomization for the radial approach is performed to compare right and left transradial access.. The RAD-MATRIX study will probably consent to clarify the radiation issue for interventional cardiologist comparing transradial and transfemoral access in the setting of acute coronary syndromes.

Topics: Absorption, Radiation; Acute Coronary Syndrome; Anticoagulants; Cardiac Catheterization; Catheterization, Peripheral; Clinical Protocols; Coronary Angiography; Europe; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Occupational Exposure; Occupational Health; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Radial Artery; Radiation Dosage; Radiography, Interventional; Recombinant Proteins; Research Design; Risk Factors; Thermoluminescent Dosimetry; Time Factors; Treatment Outcome

Bivalirudin (Angiox, The Medicine's Company, Parsippany, NJ), a synthetic direct thrombin inhibitor, when compared with standard antithrombotic therapy (including unfractionated heparin [UFH] alone or plus a glycoprotein IIb/IIIa inhibitor) determines a significant decrease of major and minor bleeding and similar protection against ischemic events both in elective and in urgent percutaneous coronary intervention (PCI). There is a lack of prospective clinical trial assessing the safety and the efficacy of bivalirudin compared with UFH alone in the subset of biomarker negative patients at high risk of bleeding undergoing to elective PCI through the femoral approach.. This is a single-center, investigator-driven, randomized, double-blind, controlled trial ( www.clinicaltrial.gov registration: NCT01465503). Consecutive patients at high bleeding risk (score ≥10 according to Nikolsky et al.) undergoing elective PCI through the femoral approach will be screened for eligibility. Included patients will be randomized (ratio 1.1) to bivalirudin (Bivalirudin group) and UFH (UFH group). The primary endpoint will be the rate of major bleeding (REPLACE 2 criteria). We expect a major bleeding rate ≥5 % in the UFH group versus a ≤3 % event rate in the Bivalirudin group. Aiming for a 0.05 alpha and 0.80 power, a total of 662 patients will be needed. This number will be increased by about 25 % (leading to a total of ≈830 patients) because of uncertainty about expected endpoint rates.. The present trial will give important information on what is the best anticoagulation regimen when performing PCI through the femoral approach in patients at high risk for bleeding.

Topics: Anticoagulants; Antithrombins; Double-Blind Method; Elective Surgical Procedures; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Research Design; Stents

Bivalirudin has emerged as a meaningful alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). To date, it is unclear whether bivalirudin has advantages in patients undergoing rotational atherectomy (RA).. The current subgroup analysis of the ROTAXUS trial compared patients receiving bivalirudin (n=129) to those receiving unfractionated heparin (UFH) (n=111). Efficacy was assessed by the frequency of periprocedural myocardial infarction (MI) and safety by the frequency of major access-site bleeding (ASB). Baseline characteristics were similar. Periprocedural MI occurred less frequently in the bivalirudin group (22% vs. 37.5%, p=0.02), while ASB did not differ significantly (2.3% vs. 5.5%, p=0.20). This effect was larger in the RA group, where bivalirudin significantly reduced periprocedural MI (15.7% vs. 38.7%, p=0.01) with a trend towards reduced major ASB (2.9% vs. 10.2%, p=0.09). In the control group without RA, bivalirudin was not superior to UFH regarding periprocedural MI (28.6% vs. 36.6%, p=0.42) and major ASB (1.7% vs. 1.7%, p=0.99).. This analysis suggests a differential benefit of bivalirudin in patients treated with RA. Patients receiving bivalirudin during RA showed significantly less periprocedural MI and fewer ASB compared to patients treated with UFH.

Topics: Aged; Anticoagulants; Antithrombins; Atherectomy, Coronary; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

Although lesion complexity is predictive of outcomes after balloon angioplasty, it is unclear whether complex lesions continue to portend a worse prognosis in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with contemporary interventional therapies. We sought to assess the impact of angiographic lesion complexity, defined by the modified American College of Cardiology/American Heart Association classification, on clinical outcomes after PCI in patients with ACS and to determine whether an interaction exists between lesion complexity and antithrombin regimen outcomes after PCI. Among the 3,661 patients who underwent PCI in the Acute Catheterization and Urgent Intervention Triage strategy study, patients with type C lesions (n = 1,654 [45%]) had higher 30-day rates of mortality (1.2% vs 0.6%, p = 0.049), myocardial infarction (9.2% vs 6.3%, p = 0.0006), and unplanned revascularization (4.3% vs 3.1%, p = 0.04) compared with those without type C lesions. In multivariate analysis, type C lesions were independently associated with myocardial infarction (odds ratio [95% confidence interval] = 1.37 [1.04 to 1.80], p = 0.02) and composite ischemia (odds ratio [95% confidence interval] = 1.49 [1.17 to 1.88], p = 0.001) at 30 days. Bivalirudin monotherapy compared with heparin plus a glycoprotein IIb/IIIa inhibitor reduced major bleeding complications with similar rates of composite ischemic events, regardless of the presence of type C lesions. There were no interactions between antithrombotic regimens and lesion complexity in terms of composite ischemia and major bleeding (p [interaction] = 0.91 and 0.80, respectively). In conclusion, patients with ACS with type C lesion characteristics undergoing PCI have an adverse short-term prognosis. Treatment with bivalirudin monotherapy reduces major hemorrhagic complications irrespective of lesion complexity with comparable suppression of adverse ischemic events as heparin plus glycoprotein IIb/IIIa inhibitor.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prognosis; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients.. Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events.. We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI -13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population.. This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.. Clinical Trials.gov NCT00798525. Registered 25 November 2008.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Arginine; Critical Illness; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Partial Thromboplastin Time; Pipecolic Acids; Recombinant Proteins; Renal Insufficiency; Renal Replacement Therapy; Sulfonamides; Surgical Procedures, Operative; Thrombocytopenia

Although the reduction in mortality with bivalirudin compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial has been attributed to lower rates of major bleeding, alternative mechanisms have not been investigated in depth. We sought to investigate whether there might be an interaction between white blood cell (WBC) count and bivalirudin for the risk of mortality, and whether this interaction is independent of major bleeding.. Among the 3602 patients enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3%) patients. Patients were stratified according to WBC tertiles. At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in patients in the upper WBC tertile (all-cause death: 4.1% versus 9.3%, respectively; P=0.0004; cardiac death: 2.0% versus 6.9%; respectively; P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles. The reduction of mortality with bivalirudin across WBC tertiles was independent of major bleeding, and a significant interaction was apparent for 1-year all-cause mortality and cardiac mortality between WBC and bivalirudin therapy. Similar findings were apparent at 3 years.. In patients with ST-segment-elevation myocardial infarction, a significant interaction between bivalirudin therapy and admission WBC count was apparent for 1-year mortality. The reduction in mortality was independent of major bleeding, suggesting that other mechanisms may be implicated in the survival benefit observed with bivalirudin.. http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Topics: Acute Disease; Aged; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Integrin beta3; Leukocyte Count; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Membrane Glycoprotein IIb; Prospective Studies; Recombinant Proteins; Survival Analysis

Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown.. We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding.. Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients.. Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.).

Topics: Adult; Aged; Anticoagulants; Antithrombins; Coronary Artery Bypass; Coronary Thrombosis; Emergency Medical Services; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Stents; Transportation of Patients

In patients with ST-segment elevation myocardial infarction (STEMI) triaged to primary percutaneous coronary intervention (PCI), anticoagulation often is initiated in the ambulance during transfer to a PCI site. In this prehospital setting, bivalirudin has not been compared with standard-of-care anticoagulation. In addition, it has not been tested in conjunction with the newer P2Y12 inhibitors prasugrel or ticagrelor.. EUROMAX is a randomized, international, prospective, open-label ambulance trial comparing bivalirudin with standard-of-care anticoagulation with or without glycoprotein IIb/IIIa inhibitors in 2200 patients with STEMI and intended for primary percutaneous coronary intervention (PCI), presenting either via ambulance or to centers where PCI is not performed. Patients will receive either bivalirudin given as a 0.75 mg/kg bolus followed immediately by a 1.75-mg/kg per hour infusion for ≥30 minutes prior to primary PCI and continued for ≥4 hours after the end of the procedure at the reduced dose of 0.25 mg/kg per hour, or heparins at guideline-recommended doses, with or without routine or bailout glycoprotein IIb/IIIa inhibitor treatment according to local practice. The primary end point is the composite incidence of death or non-coronary-artery-bypass-graft related protocol major bleeding at 30 days by intention to treat.. The EUROMAX trial will test whether bivalirudin started in the ambulance and continued for 4 hours after primary PCI improves clinical outcomes compared with guideline-recommended standard-of-care heparin-based regimens, and will also provide information on the combination of bivalirudin with prasugrel or ticagrelor.

Topics: Ambulances; Anticoagulants; Antithrombins; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Patient Transfer; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Treatment Outcome

We aimed to determine the optimal adjunctive anticoagulation regimen for percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS) initially treated with fondaparinux. The optimal adjunctive anticoagulation regimen for PCI in these patients is unclear. In this open-label, prospective, randomized, multicenter pilot study, we compared treatment with unfractionated heparin (UFH) versus bivalirudin in patients with non-ST-segment elevation ACS initially treated with fondaparinux and undergoing early invasive strategy. The randomized population consisted of 100 patients (62.7 ± 12.7 years, 68% men), all of whom were on clopidogrel. During the angioplasty, patients were randomized to either bivalirudin or UFH therapy in a 1:1 fashion. Baseline clinical and angiographic characteristics were similar except for a higher body mass index in the UFH group (29.4 ± 4.7 vs. 27.3 ± 4.2, P = 0.02). Major bleeding was the primary outcome; a major bleeding event was documented in only 1 patient from the bivalirudin group (2%) and in none from the UFH group (P = 0.49). There was no death, Q-wave MI, or acute revascularization in either group. There was no documentation of stent thrombosis, reinfarction, and catheter thrombus. Data from this prospective, multicenter pilot study suggest that bivalirudin, compared to standard-dose UFH, has a similar safety profile in terms of peri-PCI bleeding and thrombotic events and can be used safely in ACS patients initially treated with upstream fondaparinux who undergo PCI.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Female; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Pilot Projects; Polysaccharides; Prospective Studies; Recombinant Proteins; Treatment Outcome

Myocardial infarct size is a strong independent predictor of mortality in patients with ST-elevation myocardial infarction (STEMI). In the Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor reduced cardiac mortality in STEMI patients, which was attributed to reduced major bleeding. Whether a possible reduction in infarct size with bivalirudin may have contributed to the enhanced survival with this agent is unknown.. Cardiac magnetic resonance imaging was performed within 7 days and after 6 months in 51 randomized patients from a single center in HORIZONS-AMI trial (N = 28 bivalirudin, N = 23 heparin plus abciximab). Infarct size, microvascular obstruction (MVO), left ventricular ejection fraction (LVEF), and LV end-diastolic and end-systolic volume indices were evaluated.. Infarct size was not significantly different after treatment with bivalirudin compared with heparin plus abciximab either within 7 days (median 9.3% [interquartile range 4.9%, 26.6%] vs. 20.0% [5.9%, 28.2%], P = 0.28) or at 6 months 6.7% [3.8%, 20.0%] vs. 8.2% [1.8%, 16.5%], P = 0.73). MVO was present in 28.6% versus 34.8% of patients respectively (P = 0.63). LVEF and LV volume indices also did not significantly differ between the two groups at either time period, nor were differences in myocardial recovery evident.. In conclusion, in the HORIZONS-AMI Cardiac magnetic resonance imaging (CMRI) substudy, cardiac magnetic resonance imaging within 7 days and at 6 months after primary percutaneous coronary intervention (PCI) did not demonstrate significant differences in infarct size, MVO, LVEF, or LV volume indices in patients treated with bivalirudin compared with unfractionated heparin plus abciximab.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Chi-Square Distribution; Coronary Circulation; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Magnetic Resonance Imaging, Cine; Male; Microcirculation; Middle Aged; Myocardial Infarction; Myocardium; Peptide Fragments; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Recovery of Function; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Bivalirudin (BIV) is superior to a heparin/glycoprotein IIb/IIIa receptor inhibitor (GPI) strategy with respect to net adverse cardiovascular events for ST-segment elevation myocardial infarction (STEMI) percutaneous coronary intervention (PCI), albeit with an increased risk of acute stent thrombosis. We hypothesized that a 2-hour BIV infusion after PCI (BIV + 2) could be used without increased bleeding risk as a potential method of mitigating early thrombotic risk. We analyzed a 6-center regional protocol involving routine therapy with aspirin, clopidogrel, and bolus heparin followed by primary PCI for STEMI using BIV. All consecutive patients presenting with STEMI requiring primary PCI were included (2009 to 2011). We compared baseline characteristics and clinical outcomes of the University of Vermont Regional Registry to the historical groups of BIV (BIV terminated at end of PCI) or unfractionated heparin/GPI from the HORIZONS trial and determined independent predictors of bleeding. Of 346 patients undergoing PCI for STEMI, 98% received BIV; 82% of patients received BIV + 2, and 13.3% of all patients receiving BIV received GPI bailout. All-cause mortality was 3.1%. Overall bleeding rates were 50% less than in the HORIZONS GPI arm and similar to the HORIZONS BIV arm. Acute stent thrombosis occurred in <1.0% of patients. Bailout GPI was a potent independent predictor of bleeding complications. In conclusion, BIV + 2 is a feasible regional pharmacologic algorithm for STEMI PCI; BIV + 2 for STEMI PCI is not associated with increased bleeding risk and warrants further study as a mechanism of mitigating very early thrombosis risk.

Topics: Antithrombins; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Hirudins; Humans; Incidence; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Registries; Retrospective Studies; Treatment Outcome; Vermont

The optimal antithrombotic therapy for patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention is not well defined. We investigated the efficacy and safety of bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment.. This study included 3798 clopidogrel-pretreated patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention, who were randomly assigned to receive bivalirudin (n=1928) or heparin (unfractionated heparin or enoxaparin; n=1870) plus a GPI in the setting of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) and Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 4 trials. Major end points were a composite of death, recurrent myocardial infarction or urgent target vessel revascularization (efficacy end point), major bleeding (safety end point), and the composite of death, recurrent myocardial infarction, urgent target vessel revascularization, or major bleeding (net adverse clinical events [NACE]) at 30 days. The incidence of the efficacy end point was 10.6% (n=205) in the bivalirudin group versus 10.2% (n=191) in the heparin plus a GPI group (OR, 1.04; 95% CI, 0.85-1.27; P=0.69). The incidence of safety end point was 3.4% (n=66) in the bivalirudin group versus 6.3% (n=117) in the heparin plus a GPI group (OR, 0.54 [0.40-0.72]; P<0.001). NACE occurred in 258 patients (13.4%) in the bivalirudin group versus 275 patients (14.7%) in the heparin plus a GPI group (OR, 0.90 [0.76-1.06]; P=0.21).. NACE rates were not significantly different between bivalirudin and heparin plus a GPI in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment. Although no significant difference in efficacy was seen in terms of suppression of adverse ischemic events, bivalirudin was superior to heparin plus a GPI in terms of reducing bleeding events.. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00093158 and NCT00373451.

Topics: Aged; Chi-Square Distribution; Coronary Thrombosis; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Risk Factors; Treatment Outcome

Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. Sixteen patients were randomized to treatment with fixed-dose desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time-adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to direct thrombin inhibitor therapy, whereas Arm B included 8 patients on argatroban for at least 24 hours before randomization. The primary efficacy measure was the composite of new or worsening thrombosis (objectively documented), amputation, or death. Other end points included major and minor bleeding while on drug therapy, time to platelet count recovery, and pharmacoeconomics. No amputations or deaths occurred. One patient randomized to argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2 patients on argatroban and in none during desirudin treatment. There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.

Topics: Adolescent; Adult; Aged; Anticoagulants; Arginine; Disease Progression; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Pilot Projects; Pipecolic Acids; Platelet Count; Postoperative Complications; Postoperative Period; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia; Thrombosis; Treatment Outcome; Young Adult

Pediatric physicians regularly face the problem of uncertain procedural anticoagulation in children, especially in neonates. We sought to evaluate the safety, plasma concentration (pharmacokinetics, PK), pharmacodynamics (PD), and dosing guidelines of bivalirudin when used as a procedural anticoagulant in pediatric percutaneous intravascular procedures.. Pediatric subjects undergoing percutaneous intravascular procedures for congenital heart disease were enrolled and received the current weight-based dose used in percutaneous coronary interventions (0.75 mg/kg bolus, 1.75 mg/kg/hr infusion). Blood samples for PK/PD analyses were drawn, and safety was evaluated by monitoring bleeding and thrombosis events. A total of 110 patients (11 neonates, 33 infants, 32 young children, and 34 older children) were enrolled; 106 patients received the protocol dose. The PK/PD response of bivalirudin was predictable and behaved in a manner similar to that in adults. Weight-normalized bivalirudin clearance rates were more rapid in neonates and decreased with increasing age. Bivalirudin concentrations were slightly lower in neonates, with a trend to an increase with age. Activating clotting time response was consistent with adult studies and prolonged in all age groups, and there was reasonable correlation between activating clotting time and bivalirudin plasma concentrations across all age groups. There were few major bleeding (2 of 110, 1.8%) or thrombotic events (9 of 110, 8.2%) reported.. PK/PD response of bivalirudin in the pediatric population is predictable and behaves in a manner similar to that in adults. Using adult dosing, bivalirudin safely provided the expected anticoagulant effect in the pediatric population undergoing intravascular procedures for congenital heart disease.

Topics: Adolescent; Age Factors; Anticoagulants; Cardiac Catheterization; Child; Child, Preschool; Female; Heart Defects, Congenital; Hemorrhage; Hirudins; Humans; Infant; Infant, Newborn; Male; Peptide Fragments; Prospective Studies; Recombinant Proteins; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; United States

In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain.. Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 μg/kg) plus 12-hr infusion (0.15 μg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%.. With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Aspirin; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Risk Factors; Stents; Ticlopidine; Time Factors; Tirofiban; Treatment Outcome; Tyrosine; United States

We assessed the impact of smoking on outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention using alternative antithrombotic regimens and stent types. In the HORIZONS-AMI trial 3,602 patients were randomly assigned to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) or bivalirudin alone and paclitaxel-eluting stents or bare-metal stents. Compared to nonsmokers, smokers had significantly lower rates of mortality and major bleeding at 30 days and at 1 year; however, the differences were no longer significant after covariate adjustment. Smoking was associated with increased rates of definite/probable stent thrombosis (ST) at 1 year (adjusted RR 1.99, 95% confidence interval 1.28 to 3.10) mainly because of a higher rate of late ST after paclitaxel-eluting stent implantation (1.9% vs 0.4%, p = 0.0006). In smokers bivalirudin monotherapy compared to UFH plus a GPI was associated with lower mortality at 30 days (0.5% vs 2.2%, p = 0.002) and at 1 year (1.8% vs 4.0%, p = 0.008). No decrease in mortality was seen with bivalirudin in nonsmokers. Major bleeding was significantly decreased with bivalirudin regardless of smoking status (smokers 3.7% vs 8.9%, p <0.0001; nonsmokers 6.5% vs 9.6%, p = 0.01). In conclusion, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, smoking is an independent predictor of definite/probable ST at 1 year. Bivalirudin monotherapy compared to UFH plus a GPI decreased major bleeding regardless of smoking status but may have different effects on individual components of ischemic events.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Drug Utilization; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Recombinant Proteins; Smoking; Stents

This study sought to investigate the impact of chronic kidney disease (CKD) in patients undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) with different antithrombotic strategies.. CKD is associated with increased risk of adverse ischemic and hemorrhagic events after primary PCI for STEMI.. HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial was a multicenter, international, randomized trial comparing bivalirudin monotherapy or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) during primary PCI in STEMI. CKD, defined as creatinine clearance <60 ml/min, was present at baseline in 554 of 3,397 patients (16.3%). Patients were followed for 3 years. Net adverse cardiac event (NACE) was defined as the composite of death, reinfarction, ischemia-driven target vessel revascularization (TVR), stroke or non-coronary artery bypass grafting (CABG)-related major bleeding.. Patients with CKD compared with patients without had higher rates of NACE (41.4% vs. 23.8%, p < 0.0001), death (18.7% vs. 4.4%, p < 0.0001), and major bleeding (19.3% vs. 6.7%, p < 0.0001). Multivariable analysis identified baseline creatinine as an independent predictor of death at 3 years (hazard ratio: 1.51, 95% confidence interval: 1.21 to 1.87, p < 0.001). Patients with CKD randomized to bivalirudin monotherapy versus heparin plus GPI had no significant difference in major bleeding (19.0% vs. 19.6%, p = 0.72) or death (19.0% vs. 18.4%, p = 0.88) at 3 years. In patients with CKD, there was no difference in the rates of TVR in bare-metal stents (BMS) versus drug-eluting stents (DES) at 3 years (14.1% vs. 15.1%, p = 0.8).. STEMI patients with CKD have significantly higher rates of death and major bleeding compared with those without CKD. In patients with CKD, there appears to be no benefit of bivalirudin compared with heparin + GPI, or DES versus BMS during primary PCI in improving clinical outcomes.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Chi-Square Distribution; Chronic Disease; Drug-Eluting Stents; Europe; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Israel; Kaplan-Meier Estimate; Kidney Diseases; Male; Metals; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Recombinant Proteins; Recurrence; Risk Assessment; Risk Factors; Stents; Stroke; Thrombosis; Time Factors; Treatment Outcome; United States

Prior randomized trials have shown reduced bleeding with bivalirudin compared with unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI). However, it is not known if this benefit is also present when UFH doses are more tightly controlled (as measured by activated clotting time, ACT).. Patients enrolled in the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) registry, were divided into 3 groups, based on the antithrombotic drug used during PCI (UFH monotherapy, UFH+glycoprotein IIb-IIIa receptor inhibitor [GPI], or bivalirudin alone). Propensity score matching was used to adjust for measured covariates (89 variables) and to compare bivalirudin versus UFH monotherapy and bivalirudin versus UFH+GPI groups. The UFH groups were stratified based on ACT achieved (optimal ACT defined as 250-300 for UFH monotherapy and 200-250 when GPI was also used). The primary bleeding outcome was in-hospital composite bleeding, defined as events of access site bleeding, Thrombolysis In Myocardial Infarction major/minor bleeding, or transfusion. Primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/MI/unplanned repeat revascularization at 12 months) were also evaluated. Propensity score matching yielded 3022 patients for the UFH monotherapy versus bivalirudin comparison and 3520 patients for the UFH+GPI versus bivalirudin comparison. Bivalirudin use was associated with numerically lower bleeding rates at all categories of achieved ACT when compared with UFH (low, optimal, high ACT: 2.5% versus 4.7%, 1.9% versus 6.0%, 3.1% versus 4.8%, respectively) or heparin+GPI groups (low, optimal, high ACT: 0.0% versus 2.7%, 2.7% versus 5.2%, 2.4% versus 6.1%, respectively) and was not associated with any statistically significant increase in either primary or secondary ischemic outcomes.. Among unselected patients undergoing PCI, bivalirudin use during PCI was associated with a lower risk of bleeding at all comparator ACT levels without an increase in ischemic outcomes.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Drug Dosage Calculations; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Propensity Score; Recombinant Proteins; Risk; Survival Analysis; Treatment Outcome; Whole Blood Coagulation Time

The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population.. Immediately before PCI, we randomly assigned, in a double-blind manner, 1721 patients with acute non-ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days.. The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval [CI], 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02).. Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non-ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451.).

Topics: Abciximab; Adult; Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Recurrence; Thrombin

Bivalirudin, with provisional GP IIb/IIIa inhibitor use allows the same protection against ischemic complications while reducing the hemorrhagic complications compared with the systematic association of a GP IIb/IIIa inhibitor plus heparin (The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events-2 [Replace-2]). In clinical practice, the use of heparin is not systematically associated with a GP IIb/IIIa inhibitor. That's why we studied the clinical and economic interest of bivalirudin only versus heparin (UFH) only. Opened pragmatic monocentric study carried out in 2007. We made a chronological matching: for each patient treated with bivalirudin, we included the next patient with the same clinical presentation treated with unfractionated heparin. Ninety-two patients were included (46 in each group). The need for a GP IIb/IIIa inhibitor during the PCI was not significantly different between the two groups (p=0.11). No major hemorrhagic complications were observed in the two groups. Prevalence of ecchymosis was not significantly different: 22 % in the UFH group versus 13 % in the bivalirudin group (p=0.27). The average troponin level the next day was significantly higher in the bivalirudin group (p=0,049), although the change in troponin levels before and after the procedure was similar in the two groups. The average cost by patient of anticoagulation by bivalirudin and HNF is very different, respectively 473+/-150 and 51+/-146 euro (p=0.0001). Bivalirudin can be an interesting alternative for patients with a high risk of having complications. But considering its cost this therapy must be used only for selected patients.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Case-Control Studies; Drug Costs; Ecchymosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Punctures; Recombinant Proteins; Risk Factors; Treatment Outcome; Troponin

Previous studies have compared bivalirudin and unfractionated heparin (UFH) plus the routine use of glycoprotein IIb/IIIa inhibitors. They have demonstrated that bivalirudin can decrease bleeding complications without a significant increase in ischemic complications, resulting in a better net clinical outcome, as defined by the efficacy (ischemic complications) or safety (bleeding complications) end point. The aim of the present study was to compare bivalirudin and UFH plus protamine in patients undergoing elective percutaneous coronary intervention and pretreated with clopidogrel and aspirin. We randomly assigned 850 patients with stable or unstable coronary artery disease to bivalirudin or UFH followed by protamine at the end of the percutaneous coronary intervention. The primary end point was in-hospital major bleeding. The main secondary end points were the 1-month composite of death, myocardial infarction, unplanned target vessel revascularization; and the 1-month net clinical outcome. The rate of major bleeding (primary end point) was 0.5% in patients randomized to bivalirudin and 2.1% in patients randomized to UFH (p = 0.033). At 30 days, the rate of major bleeding was 0.9% in the bivalirudin arm and 2.8% in the UFH arm (p = 0.043). The composite of death, myocardial infarction, and target vessel revascularization rate and the net clinical outcome rate was 2.8% and 6.4% (p = 0.014) and 3.3% and 7.8% (p = 0.004), respectively, in the bivalirudin and UFH arms. In conclusion, in percutaneous coronary intervention patients pretreated with clopidogrel and aspirin, bivalirudin was associated with less major bleeding and fewer ischemic complications and a better net clinical outcome than UFH.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Hemostasis; Heparin; Heparin Antagonists; Hirudins; Humans; Incidence; Infusions, Intravenous; Italy; Male; Peptide Fragments; Protamines; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Replacing heparin with bivalirudin has been beneficial in patients undergoing coronary intervention and coronary artery bypass. The use of this alternative anticoagulant during peripheral bypass operations has not been studied. Concerns over distal thrombosis using this direct thrombin inhibitor (DTI) prompted a single-arm, open-label, pilot prospective trial of bivalirudin in patients undergoing lower extremity bypass to assess perioperative safety and efficacy.. Between 2006 and 2007, 18 patients met criteria for enrollment and underwent primary lower extremity bypass using bivalirudin. All patients had severe symptomatic atherosclerotic disease requiring lower extremity bypass. Bivalirudin at a bolus dose of 0.75 mg/kg and continuous infusion of 1.75 mg/kg/hr was used as the sole anticoagulant.. Patients (mean age, 67 years) underwent femoral-popliteal (n = 14) or femoral-tibial (n = 4) bypass preferentially using saphenous vein (83%). Mean operative time was 261 minutes, with bivalirudin infusion time of 95 +/- 26 minutes (mean +/- standard deviation). Reliable anticoagulation was achieved with weight-based dosing with activated clotting time values at baseline (systemic) of 131 +/- 92 seconds, during infusion (systemic) of 347 +/- 36 seconds, and from the distal vasculature (limb) of 345 +/- 66 seconds. Distal limb bivalirudin levels were stable at 9755 +/- 3860 ng/mL during clamp occlusion. Mean estimated blood loss was 332 +/- 191 mL with four patients (22%) requiring blood products. One patient required revision of the proximal anastomosis during the initial hospitalization. At 30 days, all bypass operations were patent with improvement of mean ankle-brachial index from 0.57 to 0.81. There were no deaths, myocardial infarctions, or amputations in the 30-day postoperative period. Based on the Thrombolysis in Myocardial Infarction classification for bleeding, one patient had major bleeding (>2 units of packed red blood cells), and three patients had minor bleeding within the first 30 days.. Bivalirudin is a safe and effective anticoagulant for lower extremity bypass operations. Thrombosis beyond the distal clamp was not seen. A comparative trial to standard anticoagulation is warranted.

Topics: Aged; Ankle Brachial Index; Anticoagulants; Arterial Occlusive Diseases; Blood Loss, Surgical; Hemorrhage; Hirudins; Humans; Infusions, Intravenous; Lower Extremity; Ohio; Peptide Fragments; Pilot Projects; Prospective Studies; Recombinant Proteins; Reoperation; Saphenous Vein; Thrombin; Thrombosis; Time Factors; Treatment Outcome; Vascular Patency; Vascular Surgical Procedures

This study sought to assess the relationship between 1-year mortality and baseline patient risk in the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial.. The HORIZONS-AMI trial showed that bivalirudin compared with unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decreased major bleeding and 30-day and 1-year mortality in patients undergoing primary percutaneous intervention for acute myocardial infarction.. Patients in the HORIZONS-AMI trial were classified as low, intermediate, and high risk according to the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) risk score based on 7 clinical variables.. Among 2,530 CADILLAC-score evaluable HORIZONS-AMI trial patients, 1,522 (60%) were classified as low risk, 531 (21%) as intermediate risk, and 477 (19%) as high risk. The mortality rates in the bivalirudin and UFH plus GPI arms, respectively, were 0.4% and 1.2% (p = 0.09) in the low-risk group, 4.2% and 4.1% (p = 0.99) in the intermediate-risk group, and 8.4% and 15.9% (p = 0.01) in the high-risk group. Among high-risk patients, there was also a decreased rate of recurrent myocardial infarction in patients randomized to bivalirudin as compared to UFH plus GPI (3.6% vs. 7.9%, p = 0.04).. In high-risk patients undergoing primary percutaneous coronary intervention for acute myocardial infarction, bivalirudin compared with UFH plus GPI reduces 1-year mortality and recurrent myocardial infarction. (HORIZONS-AMI trial; NCT00433966).

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antithrombins; Chi-Square Distribution; Eptifibatide; Europe; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Israel; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Patient Selection; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Prospective Studies; Recombinant Proteins; Risk Assessment; Risk Factors; Secondary Prevention; Stents; Time Factors; Treatment Outcome; United States

The aim of this study was to identify a subset of patients at high risk of bleeding or myocardial infarction from a percutaneous coronary intervention and to investigate whether such high-risk subsets derive preferential benefit from heparin or bivalirudin.. This study included 4570 patients with coronary artery disease enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment trial and randomized to receive bivalirudin or heparin. Primary outcomes were in-hospital incidence of major bleeding and 30-day incidence of myocardial infarction. Major bleeding, myocardial infarction, and bleeding plus myocardial infarction occurred in 140, 204, and 34 patients, respectively. Older age, female sex, lower body weight, low cholesterol, multi-lesion intervention, complex lesions, and heparin therapy were independent correlates of increased risk of bleeding. Multi-lesion intervention, unstable angina, and lower body weight correlated independently with increased risks of myocardial infarction. Compared with heparin, bivalirudin was associated with a reduction in major bleeding (3.1 vs. 4.6%, P = 0.008), but mostly in low-risk patients. A reduction in the bleeding risk inversely correlated with an increase in the risk of myocardial infarction with bivalirudin (R = -0.61).. Bivalirudin and unfractionated heparin have a differential effect on risk of bleeding and myocardial infarction across various subsets of patients.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Disease; Double-Blind Method; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Radiography; Recombinant Proteins; Risk Factors

This study sought to evaluate the impact of age on outcomes in patients with moderate- and high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) enrolled in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial.. Aging-associated changes in physiology and metabolism may alter the risk and benefit of therapeutic strategies from that observed in younger people.. We performed a pre-specified analysis of 30-day and 1-year outcomes in 4 age groups, overall and among those undergoing percutaneous coronary intervention (PCI).. Of 13,819 patients in the ACUITY trial, 3,655 (26.4%) were <55 years of age, 3,940 (28.5%) were 55 to 64 years of age, 3,783 (27.4%) were 65 to 74 years of age, and 2,441 (17.7%) were > or =75 years of age. Older patients had more cardiovascular risk factors and had a higher acuity at presentation. Patients age > or =75 years treated with bivalirudin alone had similar ischemic outcomes, but significantly lower rates of bleeding compared with those treated with heparin and glycoprotein IIb/IIIa inhibitors overall and in the PCI subset. The number needed to treat with bivalirudin alone to avoid 1 major bleeding event was lower in this age group (23 overall and 16 for PCI-treated patients) than in any other.. Ischemic and bleeding complications after NSTE-ACS increase with age. Although ischemic event rates are not statistically different with either bivalirudin alone or a heparin plus glycoprotein IIb/IIIa inhibitor, bleeding complications are significantly less frequent with bivalirudin alone. Because of the substantial risk of bleeding in patients age > or =75 years, the number needed to treat to avoid 1 major bleeding event using bivalirudin alone was the lowest in the elderly group, especially among those undergoing PCI.

Topics: Acute Coronary Syndrome; Aged; Aging; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Bypass; Enoxaparin; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Thrombosis; Treatment Outcome

The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes, overall and by treatment strategy, in patients with acute coronary syndromes (ACS).. In the ACUITY trial, 13,819 patients with moderate and high-risk ACS were randomised to either heparin (unfractionated or enoxaparin) plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin alone. Per operator choice, femoral access was utilised in 11,989 patients (93.8%) and radial access in 798 patients (6.2%). There was no significant difference in composite ischaemia between the radial and femoral approaches at 30 days (8.1% vs 7.5%, p=0.18) or 1 year (14.7% vs 15.5%, p=0.77), although fewer major bleeding complications occurred with the use of radial access (3.0%vs4.8%, p=0.03). Use of bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access (3.0% vs 5.8%, p<0.0001), but not with radial access (4.2% vs 2.2%, P=0.19). Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both femoral (4.1% vs 7.4%, P<0.0001) and radial (4.9% vs 7.2%, P=0.26) access.. Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia and with fewer major bleeding complications in patients with ACS managed invasively. Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces access site related major bleeding complications with femoral but not radial artery access, though non-access site related bleeding is reduced by bivalirudin monotherapy in all patients.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Blood Transfusion; Catheterization, Peripheral; Drug Therapy, Combination; Enoxaparin; Female; Femoral Artery; Hemorrhage; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Proportional Hazards Models; Punctures; Radial Artery; Recombinant Proteins; Risk Assessment; Time Factors; Treatment Outcome; Young Adult

In this substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, we investigated the relationship between chronic kidney disease (CKD) and clinical outcomes, and compared the safety and efficacy of bivalirudin monotherapy versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI).. CKD is an important predictor of prognosis in the general population. The outcomes of patients with CKD and acute coronary syndromes (ACS) have not been well studied.. In the ACUITY study, 13,819 patients with moderate- and high-risk ACS undergoing an early, invasive strategy were randomly assigned to 1 of 3 antithrombin regimens: a heparin plus a GPI, bivalirudin plus a GPI, or bivalirudin monotherapy. CKD (creatinine clearance <60 ml/min) was present in 2,469 (19.1%) of 12,939 randomized patients with baseline creatinine clearance data.. Patients with CKD had worse 30-day and 1-year clinical outcomes than those with normal renal function. There were no significant differences between bivalirudin monotherapy and heparin plus a GPI in rates of 30-day composite ischemia (11.1% vs. 9.4%, p = 0.27) and net clinical adverse outcomes (16.1% vs. 16.9%, p = 0.65). There was remarkably less major bleeding (6.2% vs. 9.8%, p = 0.008) at 30 days, but no significant difference in 1-year composite ischemia (22.0% vs. 18.9%, p = 0.10) or mortality (7.1% vs. 7.3%, p = 0.96).. In patients with ACS, CKD is associated with higher 30-day and 1-year adverse event rates. Compared with heparin plus a GPI, the use of bivalirudin monotherapy in patients with CKD results in nonstatistically different ischemic outcomes, but significantly less 30-day major bleeding.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Biomarkers; Chronic Disease; Coronary Artery Bypass; Creatinine; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Odds Ratio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Risk Assessment; Time Factors; Treatment Outcome; Triage

In the HORIZONS-AMI trial, patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who were treated with the thrombin inhibitor bivalirudin had substantially lower 30-day rates of major haemorrhagic complications and net adverse clinical events than did patients assigned to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Here, we assess whether these initial benefits were maintained at 1 year of follow-up.. Patients aged 18 years or older were eligible for enrolment in this multicentre, open-label, randomised controlled trial if they had STEMI, presented within 12 h after the onset of symptoms, and were undergoing primary PCI. 3602 eligible patients were randomly assigned by interactive voice response system in a 1:1 ratio to receive bivalirudin (0.75 mg/kg intravenous bolus followed by 1.75 mg/kg per h infusion; n=1800) or heparin plus a GPI (control; 60 IU/kg intravenous bolus followed by boluses with target activated clotting time 200-250 s; n=1802). The two primary trial endpoints were major bleeding and net adverse clinical events (NACE; consisting of major bleeding or composite major adverse cardiovascular events [MACE; death, reinfarction, target vessel revascularisation for ischaemia, or stroke]). This prespecified analysis reports data for the 1-year follow-up. Analysis was by intention to treat. Patients with missing data were censored at the time of withdrawal from the study or at last follow-up. This trial is registered with ClinicalTrials.gov, number NCT00433966.. 1-year data were available for 1696 patients in the bivalirudin group and 1702 patients in the control group. Reasons for participant dropout were loss to follow-up and withdrawal of consent. The rate of NACE was lower in the bivalirudin group than in the control group (15.6%vs 18.3%, hazard ratio [HR] 0.83, 95% CI 0.71-0.97, p=0.022), as a result of a lower rate of major bleeding in the bivalirudin group (5.8%vs 9.2%, HR 0.61, 0.48-0.78, p<0.0001). The rate of MACE was similar between groups (11.9%vs 11.9%, HR 1.00, 0.82-1.21, p=0.98). The 1-year rates of cardiac mortality (2.1%vs 3.8%, HR 0.57, 0.38-0.84, p=0.005) and all-cause mortality (3.5%vs 4.8%, HR 0.71, 0.51-0.98, p=0.037) were lower in the bivalirudin group than in the control group.. In patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin reduced the rates of net adverse clinical events and major bleeding at 1 year compared with treatment with heparin plus a GPI. This finding has important clinical implications for the selection of optimum treatment strategies for patients with STEMI.. Cardiovascular Research Foundation, with unrestricted grant support from Boston Scientific Corporation and The Medicines Company.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Proportional Hazards Models; Recombinant Proteins; Stents; Survival Rate; Thrombosis; Treatment Outcome

Bivalirudin demonstrated similar efficacy but resulted in a lower rate of bleeding compared to unfractionated heparin (UFH) plus platelet glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention. It has not been clearly evaluated whether this can also be applied to patients with diabetes mellitus. A total of 335 consecutive patients with diabetes mellitus referred for elective percutaneous coronary intervention were randomized in the Novel Approaches for Preventing or Limiting EventS (NAPLES) trial to receive bivalirudin monotherapy or UFH plus routine tirofiban. The primary composite end point (30-day composite incidence of death, urgent repeat revascularization, myocardial infarction, and all bleeding) was lower in the bivalirudin group than in the UFH plus tirofiban group (18.0% vs 31.5%, odds ratio 0.47, 95% confidence interval 0.28 to 0.79, p = 0.004). No death, urgent revascularization, or Q-wave myocardial infarction occurred. The rate of non-Q-wave myocardial infarction was similar in the 2 groups (10.2% in the bivalirudin group vs 12.5% in the UFH plus tirofiban group, p = 0.606). In contrast, fewer patients in the bivalirudin group experienced bleeding (8.4% vs 20.8%, odds ratio 0.34, 95% confidence interval 0.18 to 0.67, p = 0.002). This difference was mainly ascribed to the lower rate of minor bleeding (7.8% in the bivalirudin group vs 18.5% in the UFH plus tirofiban group, odds ratio 0.37, 95% confidence interval 0.19 to 0.74, p = 0.005), although the rate of major bleeding in the 2 groups was comparable (0.6% vs 2.4%, respectively; p = 0.371). In conclusion, in patients with diabetes mellitus undergoing elective percutaneous coronary intervention, the strategy of bivalirudin monotherapy compared to UFH plus routine tirofiban is safe and feasible and associated with a significant reduction of in-hospital bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Prospective Studies; Recombinant Proteins; Retreatment; Thrombocytopenia; Tirofiban; Tyrosine

Whether bivalirudin is superior to unfractionated heparin in patients with stable or unstable angina who undergo percutaneous coronary intervention (PCI) after pretreatment with clopidogrel is unknown.. We enrolled 4570 patients with stable or unstable angina (with normal levels of troponin T and creatine kinase MB) who were undergoing PCI after pretreatment with a 600-mg dose of clopidogrel at least 2 hours before the procedure; 2289 patients were randomly assigned in a double-blind manner to receive bivalirudin, and 2281 to receive unfractionated heparin. The primary end point was the composite of death, myocardial infarction, urgent target-vessel revascularization due to myocardial ischemia within 30 days after randomization, or major bleeding during the index hospitalization (with a net clinical benefit defined as a reduction in the incidence of the end point). The secondary end point was the composite of death, myocardial infarction, or urgent target-vessel revascularization.. The incidence of the primary end point was 8.3% (190 patients) in the bivalirudin group as compared with 8.7% (199 patients) in the unfractionated-heparin group (relative risk, 0.94; 95% confidence interval [CI], 0.77 to 1.15; P=0.57). The secondary end point occurred in 134 patients (5.9%) in the bivalirudin group and 115 patients (5.0%) in the unfractionated-heparin group (relative risk, 1.16; 95% CI, 0.91 to 1.49; P=0.23). The incidence of major bleeding was 3.1% (70 patients) in the bivalirudin group and 4.6% (104 patients) in the unfractionated-heparin group (relative risk, 0.66; 95% CI, 0.49 to 0.90; P=0.008).. In patients with stable and unstable angina who underwent PCI after pretreatment with clopidogrel, bivalirudin did not provide a net clinical benefit (i.e., it did not reduce the incidence of the composite end point of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding) as compared with unfractionated heparin, but it did significantly reduce the incidence of major bleeding. (ClinicalTrials.gov number, NCT00262054.)

Topics: Aged; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Premedication; Recombinant Proteins; Recurrence; Risk; Stents; Thrombosis; Ticlopidine

This study sought to determine if the efficacy of bivalirudin alone versus heparin plus a glycoprotein (GP) IIb/IIIa inhibitor is dependent upon the duration of clopidogrel pre-treatment in patients undergoing percutaneous coronary intervention (PCI) in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.. The administration of a clopidogrel loading dose several hours before PCI reduces the risk of periprocedural thrombotic events.. Patients with an acute coronary syndrome were randomized to heparin plus a GP IIb/IIIa inhibitor (control), bivalirudin plus a GP IIb/IIIa inhibitor, or bivalirudin alone. Dose and timing of clopidogrel were left to the investigator's discretion.. Of 13,819 patients randomized, 7,789 underwent PCI. When clopidogrel was initiated at any time before angiography or within 30 min after PCI, randomization to bivalirudin alone (n = 2,284) or control (n = 2,189) was associated with similar ischemic outcomes (8.2% vs. 8.3%, risk ratio: 0.98, 95% confidence interval: 0.81 to 1.20). Those patients who received clopidogrel >30 min after PCI or not at all experienced an increase in ischemic events when randomized to bivalirudin alone (n = 290) versus control (n = 317) (14.1% vs. 8.5%, risk ratio: 1.66, 95% confidence interval: 1.05 to 2.63). Major bleeding was significantly less frequent in patients treated with bivalirudin alone.. This post-hoc analysis suggests that in acute coronary syndrome patients, as long as clopidogrel is administered before or within 30 min of PCI treatment with bivalirudin alone is similarly effective to heparin plus a GP IIb/IIIa inhibitor in suppressing 30-day ischemic events with significantly less bleeding. If it is anticipated that clopidogrel will be given late or not at all after PCI, bivalirudin alone may be associated with worse ischemic outcomes. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158).

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Coronary Angiography; Drug Administration Schedule; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Thrombosis; Ticlopidine; Time Factors; Treatment Outcome; Troponin; Young Adult

Treatment with the direct thrombin inhibitor bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in similar suppression of ischemia while reducing hemorrhagic complications in patients with stable angina and non-ST-segment elevation acute coronary syndromes who are undergoing percutaneous coronary intervention (PCI). The safety and efficacy of bivalirudin in high-risk patients are unknown.. We randomly assigned 3602 patients with ST-segment elevation myocardial infarction who presented within 12 hours after the onset of symptoms and who were undergoing primary PCI to treatment with heparin plus a glycoprotein IIb/IIIa inhibitor or to treatment with bivalirudin alone. The two primary end points of the study were major bleeding and combined adverse clinical events, defined as the combination of major bleeding or major adverse cardiovascular events, including death, reinfarction, target-vessel revascularization for ischemia, and stroke (hereinafter referred to as net adverse clinical events) within 30 days.. Anticoagulation with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in a reduced 30-day rate of net adverse clinical events (9.2% vs. 12.1%; relative risk, 0.76; 95% confidence interval [CI] 0.63 to 0.92; P=0.005), owing to a lower rate of major bleeding (4.9% vs. 8.3%; relative risk, 0.60; 95% CI, 0.46 to 0.77; P<0.001). There was an increased risk of acute stent thrombosis within 24 hours in the bivalirudin group, but no significant increase was present by 30 days. Treatment with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in significantly lower 30-day rates of death from cardiac causes (1.8% vs. 2.9%; relative risk, 0.62; 95% CI, 0.40 to 0.95; P=0.03) and death from all causes (2.1% vs. 3.1%; relative risk, 0.66; 95% CI, 0.44 to 1.00; P=0.047).. In patients with ST-segment elevation myocardial infarction who are undergoing primary PCI, anticoagulation with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in significantly reduced 30-day rates of major bleeding and net adverse clinical events. (ClinicalTrials.gov number, NCT00433966 [ClinicalTrials.gov].).

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Combined Modality Therapy; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Recurrence; Stents; Stroke; Thrombosis

The REPLACE-2 trial of patients who underwent urgent or elective percutaneous coronary intervention (PCI) demonstrated a significantly lower bleeding risk with bivalirudin plus provisional glycoprotein IIb/IIIa inhibitor compared with unfractionated heparin with planned glycoprotein IIb/IIIa inhibitor. The goal of this analysis was to evaluate whether a hazard existed when unfractionated heparin or low-molecular-weight heparin was administered before study medication in the REPLACE-2 trial. The REPLACE-2 trial randomized 6,010 patients undergoing PCI to receive bivalirudin plus provisional glycoprotein IIb/IIIa inhibitor or unfractionated heparin plus planned glycoprotein IIb/IIIa inhibitor. The present study compared bleeding among patients treated with or without antithrombin therapy in the 48 hours before study treatment. Among patients treated with bivalirudin, there was no difference in protocol-defined major or minor bleeding, bleeding according to Thrombolysis In Myocardial Infarction criteria, or noncoronary artery bypass graft blood transfusions between the patients treated with versus without antithrombin therapy (p=NS). However, in patients treated with unfractionated heparin plus planned glycoprotein IIb/IIIa inhibitor, there was a significant increase in the composite of protocol-defined major or minor bleeding and in noncoronary artery bypass graft blood transfusions (p<0.05 for 3-way comparison vs no unfractionated heparin and for 2-way comparisons of no unfractionated heparin vs unfractionated heparin or low-molecular-weight heparin). In conclusion, in patients treated with bivalirudin, pretreatment with antithrombin therapy was not associated with increased bleeding. In contrast, among patients randomized to receive unfractionated heparin and planned glycoprotein IIb/IIIa, pretreatment with antithrombin therapy was associated with increased protocol-defined composite major or minor bleeding and increased need for transfusion.

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Eptifibatide; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Immunoglobulin Fab Fragments; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

Patients undergoing percutaneous coronary intervention (PCI) have a significant risk of hemorrhagic complications. Predictors of major hemorrhage and its relation to mortality in PCI are not well defined. Baseline and periprocedural predictors of major hemorrhage and its impact on mortality in patients undergoing elective or urgent PCI randomly assigned to heparin plus planned glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin plus provisional GPIs in the REPLACE-2 Trial were determined. Of 6,001 patients, 3.2% experienced a major hemorrhage. Independent baseline predictors of major hemorrhage included advanced age, female gender, impaired creatinine clearance, and anemia. Independent periprocedural predictors of major hemorrhage included treatment with heparin plus GPI, increased procedural duration, provisional use of GPI, increased time to sheath removal, length of intensive care unit stay, and use of an intra-aortic balloon pump (all p <0.05). Mortality rates were higher in patients with than without major hemorrhage at 30 days (5.1% vs 0.2%), 6 months (6.7% vs 1.0%), and 1 year (8.7% vs 1.9%; p <0.001 for all). Furthermore, major hemorrhage was an independent predictor of 1-year mortality (odds ratio 2.66, 95% confidence interval 1.44 to 4.92, p = 0.002). In conclusion, in patients undergoing elective or urgent PCI, major hemorrhage was an independent predictor of 1-year mortality. A number of baseline and periprocedural factors independently predicted major hemorrhage, including treatment with heparin plus GPI.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Disease; Female; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Peptide Fragments; Prospective Studies; Recombinant Proteins

Enoxaparin is an established therapy for the treatment of patients with acute coronary syndrome (ACS), and bivalirudin is commonly used as the antithrombotic agent during percutaneous coronary intervention (PCI). This study was designed to examine the safety of switching from enoxaparin to bivalirudin in these patients.. The Switching from Enoxaparin to Bivalirudin in Patients with Acute Coronary Syndromes without ST-segment Elevation Undergoing Percutaneous Coronary Intervention (SWITCH) trial was a prospective, open-label, multicenter study including 91 patients who presented with an ACS without ST-segment elevation, and who had received greater than or equal to 1 dose of enoxaparin (1 mg/kg SC) within the 12 hours prior to PCI. Patients were enrolled into 3 time categories: Group 1: 0-4; Group 2: 4-8; and Group 3: 8-12 hours from last enoxaparin dose to PCI. The primary endpoint of the study was major bleeding complications.. Baseline characteristics and average number of enoxaparin injections prior to PCI were similar in all 91 patients and among the groups. There was no occurrence of death, Q-wave myocardial infarction (MI), or acute revascularization in any group and no incidence of intracranial or retroperitoneal bleeding. The overall rate of major bleeding (7.7%) was comparable among groups (p = 0.39), as was the incidence of periprocedural non-Q-wave MI (overall 12%; p = 0.58), irrespective of the time interval between enoxaparin and bivalirudin administration.. Switching from enoxaparin to bivalirudin for patients with ACS undergoing PCI appears to be clinically safe without increased risk of major bleeding complications, regardless of the time of enoxaparin administration, and is safe enough to warrant testing it in larger numbers.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Disease; Enoxaparin; Female; Hemorrhage; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Retreatment; Risk Assessment; Syndrome

Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients.. We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding.. Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P=0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P=0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97).. In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158 [ClinicalTrials.gov].).

Topics: Adult; Aged; Aged, 80 and over; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Bypass; Drug Therapy, Combination; Enoxaparin; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

Among patients who undergo percutaneous coronary intervention, renal impairment is associated with an excessive risk of bleeding and ischemic events. Bivalirudin provides comparable suppression of ischemic events with a decrease in bleeding events compared with heparin and glycoprotein IIb/IIIa inhibition. We examined the relation between adverse events, renal impairment, and antithrombotic therapy within a randomized comparison. The Second Randomized Evaluation in PCI Linking Bivalirudin to Reduced Clinical Events per-protocol study population was assessed. Renal function was defined as calculated creatinine clearance <60 ml/min. Events within the overall study population and within each study arm were assessed. Thirty-day events by renal function were compared by chi-square test and logistic regression. Late mortality was compared by log-rank test. Interaction analyses were performed. Among 5,710 patients, renal impairment was associated with increased ischemic events (hazard ratio 1.45, 95% confidence interval 1.13 to 1.88, p = 0.004), bleeding complications (hazard ratio 1.72, 95% confidence interval 1.06 to 2.80, p = 0.028), and excessive 12-month mortality (hazard ratio 3.85, 95% confidence interval 2.67 to 5.54, p <0.001). Bivalirudin provided suppression of ischemic events that was comparable to heparin and glycoprotein IIb/IIIa inhibition regardless of renal impairment. Fewer bleeding events with bivalirudin were also evident irrespective of renal dysfunction. No interaction between treatment assignment, bleeding or ischemic complications, and renal impairment was observed. The safety and efficacy of bivalirudin compared with heparin and planned glycoprotein IIb/IIIa inhibition in this high-risk group are comparable and consistent with the results of the overall trial.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Atherectomy, Coronary; Chi-Square Distribution; Double-Blind Method; Drug Therapy, Combination; Eptifibatide; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Intraoperative Complications; Ischemia; Logistic Models; Male; Middle Aged; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Renal Insufficiency; Stents; Survival Analysis; Treatment Outcome

Predictors of complications in peripheral percutaneous interventions (PPI) with bivalirudin as a base anticoagulant have not yet been defined. The Angiomax Peripheral Procedure Registry of Vascular Events (APPROVE) offers a unique opportunity to analyze predictors of complications with bivalirudin in PPI.. APPROVE was a prospective, open-label, multi-center clinical trial that assessed the feasibility of bivalirudin in renal, iliac and femoral interventions. Bivalirudin was administered intravenously at a dose of 0.75 mg per kg bolus followed by an infusion of 1.75 mg per kg per hour for the duration of the procedure. Glycoprotein (GP) IIb-IIIa inhibitors were permitted at the discretion of the treating physician. Multiple independent variables were included in a Logistic Regression model to determine predictors of the combined endpoints of ischemic (death, amputation, unplanned urgent revascularization at the treated site, myocardial infarction) and major bleeding or major bleeding alone, assessed during hospitalization and at 30 days.. Predictors of in-hospital ischemic and major bleed events were congestive heart failure (p = 0.0173) and exchanges to larger sheath size (ELS) (p = 0.0045). The strongest predictor of major bleeding alone at discharge (p = 0.0041) and at 30 days (p = 0.0016) was the number of ELS. Also, female gender (p = 0.08) and low weight (stratified by gender with < 80 kg versus > 92 kg for males and < 62 kg versus > 77 kg for females) (p = 0.096) showed a trend toward predicting major bleeding at 30 days. Of 505 patients in APPROVE, 26 patients required more than one sheath exchange. Of these, 24 were ELS. Despite this small number, these patients accounted for most of the major bleeding events that occurred (11.5% versus 1.7% in-hospital bleeding for the patients with ELS versus single sheath use respectively, and 15.4% versus 3.1% for 30-day bleeding). GP IIb-IIIa inhibitors (n = 22) use and thrombotic lesions (3%) were not predictors of ischemic and/or bleeding complications.. ELS during PPI is a strong predictor of bleeding events when bivalirudin is used as a base anticoagulant. Female gender and low weight also tend to contribute to major bleeding.

Topics: Aged; Anticoagulants; Catheterization, Peripheral; Feasibility Studies; Female; Femoral Artery; Hemorrhage; Hirudins; Hospitalization; Humans; Iliac Artery; Ischemia; Male; Peptide Fragments; Prospective Studies; Recombinant Proteins; Registries; Renal Artery; Risk Factors; Time Factors; Treatment Outcome

To assess efficacy and safety of lepirudin in patients with heparin-induced thrombocytopenia (HIT) in a prospective study (HAT-3) as well as in a combined analysis of all HAT study data.. Patients with laboratory-confirmed HIT were treated with lepirudin in three different aPTT-adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic complications (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison.. After start of lepirudin in 205 patients treated in HAT-3, the combined endpoint occurred in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occurred. Major bleeding occurred in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start of lepirudin treatment, the combined endpoint occurred in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with the historical control group (log-rank test), the combined endpoint after start of treatment was reduced (29.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg(-1) h(-1). Major bleeding was more frequent in the lepirudin-treated patients (29.4% vs. 9.1%, P = 0.0148).. The rate of new TECs in HIT patients is low after start of lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg(-1) h(-1).

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Secondary Prevention; Survival Analysis; Thrombocytopenia; Thromboembolism

The purpose of this study was to assess if clopidogrel pretreatment affects the relative efficacy of bivalirudin versus heparin with glycoprotein (GP) IIb/IIIa blockade for percutaneous coronary interventions (PCI).. Although thienopyridine pretreatment may improve clinical outcomes with PCI, it is unknown if bivalirudin's efficacy compared with heparin is dependent upon such pretreatment.. The Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to reduced Clinical Events (REPLACE-2) trial was a double-blind, triple-dummy, randomized-controlled trial comparing heparin plus routine GP IIb/IIIa blockade (heparin group) with bivalirudin plus provisional GP IIb/IIIa blockade (bivalirudin group) during PCI. The primary end point was a composite of death, myocardial infarction (MI), urgent revascularization at 30 days, and major in-hospital bleeding. The secondary end point was a 30-day composite of death, MI, and urgent revascularization. Clopidogrel pretreatment was encouraged (300 mg loading, 75 mg/day).. Of 6,010 patients enrolled, 5,893 received clopidogrel, with 85.8% in the bivalirudin and 84.6% in the heparin group receiving clopidogrel pretreatment. Bivalirudin (provisional GP IIb/IIIa blockade 7.2%) was noninferior to the heparin group for both primary and secondary end points. Clopidogrel pretreatment did not affect the relative efficacy of bivalirudin versus heparin with GP IIb/IIIa blockade, irrespective of pretreatment duration. Pretreatment was associated with significantly lower primary end point with bivalirudin (8.7% pretreatment vs. 12.9% no pretreatment, p = 0.007), and nonsignificantly with heparin (9.7% vs. 11.7%, respectively, p = 0.20). Multivariable models showed a trend toward lower primary and secondary end points with clopidogrel pretreatment.. Clopidogrel pretreatment at the doses and time administered in this trial did not influence the relative efficacy of bivalirudin versus heparin plus GP IIb/IIIa blockade for PCI. However, pretreatment was associated with a trend towards lower clinical events after PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clopidogrel; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Endpoint Determination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Survival Analysis; Ticlopidine; Treatment Outcome

The direct thrombin inhibitor bivalirudin has been associated with better efficacy and less bleeding than heparin during coronary balloon angioplasty but has not been widely tested during contemporary percutaneous coronary intervention (PCI).. To determine the efficacy of bivalirudin, with glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition on a provisional basis for complications during PCI, compared with heparin plus planned Gp IIb/IIIa blockade with regard to protection from periprocedural ischemic and hemorrhagic complications.. The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, a randomized, double-blind, active-controlled trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002.. Patients were randomly assigned to receive intravenous bivalirudin (0.75-mg/kg bolus plus 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition (n = 2999), or heparin (65-U/kg bolus) with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide) (n = 3011). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI.. The primary composite end point was 30-day incidence of death, myocardial infarction, urgent repeat revascularization, or in-hospital major bleeding; the secondary composite end point was 30-day incidence of death, myocardial infarction, or urgent repeat revascularization.. Provisional Gp IIb/IIIa blockade was administered to 7.2% of patients in the bivalirudin group. By 30 days, the primary composite end point had occurred among 9.2% of patients in the bivalirudin group vs 10.0% of patients in the heparin-plus-Gp IIb/IIIa group (odds ratio, 0.92; 95% confidence interval, 0.77-1.09; P =.32). The secondary composite end point occurred in 7.6% of patients in the bivalirudin vs 7.1% of patients in the heparin-plus-Gp IIb/IIIa groups (odds ratio, 1.09; 95% confidence interval 0.90-1.32; P =.40). Prespecified statistical criteria for noninferiority to heparin plus Gp IIb/IIIa were satisfied for both end points. In-hospital major bleeding rates were significantly reduced by bivalirudin (2.4% vs 4.1%; P<.001).. Bivalirudin with provisional Gp IIb/IIIa blockade is statistically not inferior to heparin plus planned Gp IIb/IIIa blockade during contemporary PCI with regard to suppression of acute ischemic end points and is associated with less bleeding.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Atherectomy, Coronary; Double-Blind Method; Drug Therapy, Combination; Eptifibatide; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Intraoperative Complications; Ischemia; Male; Middle Aged; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Stents; Survival Analysis; Treatment Outcome

The Thrombolysis in Myocardial Infarction (TIMI) 8 trial was undertaken to compare the efficacy and safety of bivalirudin versus unfractionated heparin in a double-blind phase III trial of patients with unstable angina/non-ST-elevation myocardial infarction (MI).. All patients received aspirin and were randomized either to unfractionated heparin (bolus of 70 U/kg followed by an infusion of 15 U/kg/h) or bivalirudin (bolus of 0.1 mg/kg followed by an infusion of 0.25 mg/kg/h) for a minimum of 72 hours. The primary efficacy end point was a composite of all cause mortality or nonfatal recurrent MI.. A total of 133 of the planned 5320 patients were enrolled, at which point the study was terminated by the sponsor because of a decision at the time to suspend further development of bivalirudin. Through 14 days, the incidence of death or nonfatal MI was 9.2% in the 65 patients in the unfractionated heparin group and was 2.9% in the 68 patients in the bivalirudin group, odds ratio (95% CI) 0.30 (0.06-1.53). Major hemorrhage occurred in 3 patients in the unfractionated heparin group (4.6%) but in none of the patients in the bivalirudin group (P =.11).. The trend toward a lower rate of death or nonfatal MI in the bivalirudin group is consistent with a therapeutic effect of the drug and is consistent with other trials of bivalirudin in patients with acute coronary syndromes. The potential for clinically meaningful antithrombotic activity without an increased risk of bleeding and availablility of an alternative anticoagulation strategy in patients who cannot tolerate unfractionated heparin are particularly attractive and underscore the need for further evaluation of bivalirudin.

Topics: Aged; Angina, Unstable; Anticoagulants; Antithrombins; Double-Blind Method; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Myocardial Infarction; Odds Ratio; Peptide Fragments; Recombinant Proteins; Recurrence

To compare the efficacy and safety of hirudin and heparin for anticoagulation during continuous renal replacement therapy (CRRT) in critically ill patients.. Prospective, randomized controlled pilot study.. Single centre; interdisciplinary intensive care unit at a university hospital.. Seventeen patients receiving CRRT.. Patients were randomly allocated to two groups. Heparin group (nine patients): continuous administration of 250 IU/h heparin; dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180-210 s. Hirudin group (eight patients): continuous infusion of 10 micrograms/kg/h hirudin, dose was adjusted in 2 micrograms/kg/h steps with a targeted ecarin clotting time (ECT) of 80-100 s. Observation time was 96 h.. Measured filter run patency and haemofiltration efficacy did not significantly differ between the two groups. Three bleeding complications were observed in the hirudin group, none in the heparin group (P < 0.01). At the onset of bleeding, which occurred 60 or more hours after the start of therapy, only one patient was still under continuous hirudin administration but levels were either in therapeutic range or below.. Hirudin can be used efficiently for anticoagulation in CRRT. Late bleeding complications may have been caused by possible hirudin accumulation, but this was not evident from hirudin plasma and ECT levels. Since bleeding complications were observed only in the presence of documented coagulation disorders, not only adequate drug monitoring but also the plasmatic and cellular coagulation status of the patient should be taken into consideration for adjusting hirudin dosage.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anticoagulants; APACHE; Blood Coagulation Disorders; Blood Coagulation Tests; Combined Modality Therapy; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Renal Replacement Therapy

Heparin-induced thrombocytopenia (HIT) is a hypercoagulable syndrome strongly associated with thrombosis that is usually treated with drugs that inhibit factor Xa (danaparoid) or thrombin (lepirudin). In the present study the outcome of HIT-patients treated with danaparoid or lepirudin was compared using the single or combined endpoints of new thromboembolic complications (new TECs), amputations and/or death, and major bleeding. HIT-patients treated with lepirudin were enrolled in two prospective trials and patients, who were identified in the same two laboratories during the same time period, who were not enrolled into these studies but treated with danaparoid, were assessed retrospectively according to a standardized questionnaire. 126 danaparoid (60.3% female) and 175 lepirudin treated patients (58.3% female) fulfilled the same inclusion and exclusion criteria. In a time-to-event-analysis the cumulative risk of combined endpoint was higher in HIT-patients without thromboembolic complication at baseline treated with danaparoid (usually in prophylactic dose 750 anti-factor Xa units b.i.d. or t.i.d.s.c.) as compared to lepirudin (aPTT adjusted) (P = 0.020). Whereas HIT-patients with TEC at baseline who were usually treated with therapeutic dose had a similar outcome in both treatment groups (P = 0.913). Major bleeding occurred in 2.5% (95% CI 0.5-7.0%) of danaparoid treated patients as compared to 10.4% (95% CI 6.3-15.9%) of lepirudin treated patients until day 42 (P = 0.009). This indicates that the efficacies of therapeutic doses of danaparoid or lepirudin in preventing death, amputation or new TEC in HIT-patients do not differ largely, but the risk of bleeding seems to be higher in lepirudin treated patients. The prophylactic dose of danaparoid approved in the European Union for HIT without TEC at baseline seems suboptimal. A prospective comparative trial is required to verify these preliminary conclusions.

Topics: Age Factors; Aged; Amputation, Surgical; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Evaluation; Female; Hemorrhage; Heparin; Heparitin Sulfate; Hirudins; Humans; Incidence; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Surveys and Questionnaires; Thrombocytopenia; Thromboembolism; Treatment Outcome

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Cost-Benefit Analysis; Drug Costs; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Recurrence; Thrombolytic Therapy

Despite the use of heparin and aspirin, 5-10% of patients with unstable angina develop myocardial infarction or refractory angina in hospital. We tested the hypothesis that recombinant hirudin (lepirudin), a direct thrombin inhibitor, would be superior to heparin, an indirect thrombin inhibitor, in patients with acute ischaemic syndromes who were receiving aspirin.. 10,141 patients with unstable angina or suspected acute myocardial infarction without ST elevation were randomly assigned heparin (5000 units bolus then 15 units kg(-1) h(-1); n=5058) or hirudin (0.4 mg/kg bolus then 0.15 mg kg(-1) h(-1) infusion; n=5083) for 72 h in a double-blind trial. The primary outcome measure was cardiovascular death or new myocardial infarction at 7 days. Analysis was by intention to treat.. At 7 days, 213 (4.2%) patients in the heparin group and 182 (3.6%) in the hirudin group had experienced cardiovascular death or new myocardial infarction (relative risk 0.84 [95% CI 0.69-1.02]; p=0.077). The numbers with cardiovascular death, new myocardial infarction, or refractory angina at 7 days were 340 (6.7%) with heparin and 284 (5.6%) with hirudin (0.82 [0.70-0.96]; p=0.0125). These differences were primarily observed during the 72 h treatment period (cardiovascular death or myocardial infarction relative risk 0.76 [0.59-0.99], p=0.039: cardiovascular death, myocardial infarction, or refractory angina 0.78 [0.63-0.96], p=0.019). Although there was an excess of major bleeding requiring transfusion with hirudin (59 [1.2%] vs 34 [0.7%] with heparin; p=0.01), there was no excess in life-threatening episodes (20 in each group) or strokes (14 in each group).. The data from OASIS-2 suggest that recombinant hirudin is superior to heparin in preventing cardiovascular death, myocardial infarction, and refractory angina with an acceptable safety profile in patients with unstable angina or acute myocardial infarction without ST elevation. Thus, a direct thrombin inhibitor is more effective than an indirect thrombin inhibitor.

Topics: Angina, Unstable; Cardiovascular Diseases; Double-Blind Method; Electrocardiography; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Recombinant Proteins; Risk Factors; Treatment Outcome

We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT).. Patients with confirmed HIT (n=112) received lepirudin according to need for 2 to 10 days (longer if necessary): A1, treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg. kg(-1). h(-1) intravenous infusion, n=65; A2, treatment in conjunction with thrombolysis: 0.2 mg/kg, followed by 0.10 mg. kg(-1). h(-1), n=4; and B, prophylaxis: 0.10 mg. kg(-1). h(-1), n=43. Outcomes from 95 eligible lepirudin-treated patients were compared with those of historical control patients (n=120). Complete laboratory response (activated partial thromboplastin time ratio >1.5 with /=1 outcome (cumulative incidence 30.9% versus 52.1%; relative risk [RR] 0.71; P=0.12, log-rank test). Bleeding events were more frequent in the lepirudin group than the historical control group (cumulative incidence at 35 days, 44.6% versus 27.2%; RR 2.57; P=0.0001, log-rank test). No difference was observed in bleeding events requiring transfusion (cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66; P=0.23, log-rank test); no intracranial bleeding was observed in the lepirudin group.. Lepirudin effectively prevents death, limb amputations, and new thromboembolic complications and has an acceptable safety profile in HIT patients. Treatment should be initiated as soon as possible if HIT is suspected.

Topics: Aged; Amputation, Surgical; Anticoagulants; Autoimmune Diseases; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Life Tables; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Recurrence; Safety; Survival Analysis; Thrombocytopenia; Thrombosis; Treatment Outcome

Patients with acute ischemic syndromes (AIS) suffer high rates of recurrent ischemic events despite aspirin treatment. Long-term therapy with oral anticoagulants in addition to aspirin may reduce this risk. We studied the effects of long-term warfarin at 2 intensities in patients with AIS without ST elevation in 2 consecutive randomized controlled studies.. In phase 1, after the cessation of 3 days of intravenous antithrombotic therapy, 309 patients were randomized to receive fixed low-dose (3 mg/d) warfarin for 6 months that produced a mean international normalized ratio (INR) of 1.5+/-0.6 or to standard therapy. Eighty-seven percent of patients received aspirin in both groups. The rates of cardiovascular (CV) death, new myocardial infarction (MI), and refractory angina at 6 months were 6.5% in the warfarin group and 3.9% in the standard therapy group (relative risk [RR], 1. 66; 95% CI, 0.62 to 4.44; P=0.31). The rates of death, new MI, and stroke were 6.5% in the warfarin group and 2.6% in the standard therapy group (RR, 2.48; 95% CI, 0.80 to 7.75; P=0.10). The overall rate of rehospitalization for unstable angina was 21% and did not differ significantly between the groups. Four patients in the warfarin group (2.6%) and none in the control group experienced a major bleed (RR, 2.48; 95% CI, 0.80 to 7.75), and there was a significant excess of minor bleeds in the warfarin group (14.2% versus 2.6%; RR, 5.46; 95% CI, 1.93 to 15.5; P=0.001). In phase 2, the protocol was modified, and 197 patients were randomized <48 hours from the onset of symptoms to receive warfarin at an adjusted dose that produced a mean INR of 2.3+/-0.6 or standard therapy for 3 months. Eighty-five percent received aspirin in both groups. The rates of CV death, new MI, and refractory angina at 3 months were 5. 1% in the warfarin group and 12.1% in the standard group (RR, 0.42; 95% CI, 0.15 to 1.15; P=0.08). The rates of all death, new MI, and stroke were 5.1% in the warfarin group and 13.1% in the standard therapy group (RR, 0.39; 95% CI, 0.14 to 1.05; P=0.05). Significantly fewer patients were rehospitalized for unstable angina in the warfarin group than in the control group (7.1% and 17.2%, respectively; RR, 0.42; 95% CI, 0.18 to 0.96; P=0.03). Two patients in the warfarin group and 1 in the control group experienced a major bleed, and there was a significant excess of minor bleeds in the warfarin group (28.6% versus 12.1%; RR, 2.36; 95% CI, 1.37 to 4.36; P=0.004).. Long-term treatment with moderate-intensity warfarin (INR, 2.0 to 2.5) plus aspirin but not low-intensity warfarin (INR, 1.5) plus aspirin appears to reduce the rate of recurrent ischemic events in patients with AIS without ST elevation.

Topics: Administration, Oral; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Aspirin; Coronary Artery Bypass; Electrocardiography; Hemorrhage; Hirudins; Humans; Infusions, Intravenous; Myocardial Infarction; Myocardial Ischemia; Patient Compliance; Pilot Projects; Platelet Aggregation Inhibitors; Warfarin

The outcome of coronary angioplasty performed for unstable angina is determined, in part, by the acuteness and severity of the clinical presentation. The risk of abrupt vessel closure is increased in patients with postinfarction angina. The Hirulog Angioplasty Study compared the efficacy and safety of bivalirudin with weight-adjusted heparin in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) for unstable or postinfarction angina. We report the results of the intent-to-treat analysis using adjudicated data for the prespecified group of 741 patients who underwent angioplasty within 2 weeks of documented myocardial infarction. Patients received either bivalirudin or heparin immediately before angioplasty. The primary efficacy endpoint was procedural failure defined as abrupt vessel closure, death, myocardial infarction, or revascularization during hospitalization. Bivalirudin significantly (p = 0.004) decreased the incidence of procedural failure compared with heparin (5.1% vs 10.8%, odds ratio 0.45; 95% CI 0.25-0.79). The improved efficacy of bivalirudin was replicated for each individual clinical endpoint. The incidence of major bleeding was significantly (p = 0.001) lower in bivalirudin-treated patients compared with heparin-treated patients (2.4% vs 11.8%, respectively). The benefits observed with bivalirudin are of similar magnitude as those reported for platelet glycoprotein (GP) IIb/IIIa inhibitors, such as abciximab. Bivalirudin may be a more effective foundation anticoagulant than heparin in patients undergoing coronary angioplasty for postinfarction angina.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Double-Blind Method; Drug Monitoring; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Treatment Outcome

The dosing of anticoagulants during coronary angioplasty is commonly guided by measurements of activated clotting time (ACT), but the usefulness of these measurements remains uncertain. The Hirulog Angioplasty Study was a randomized, double-blind comparison of heparin versus bivalirudin in 4,312 patients undergoing angioplasty for unstable or postinfarction angina. In 4,098 of the patients randomized, the balloon was inflated. All patients had ACT measurements 5 minutes after a weight-adjusted bolus of heparin or bivalirudin, and patients undergoing complicated or prolonged angioplasty procedures lasting >45 minutes had additional ACT measurements to guide further anticoagulant therapy. The analysis presented in this article evaluated the relation between the initial or maximum ACT measurements and the risk of abrupt vessel closure during heparin or bivalirudin therapy. Abrupt vessel closure occurred in 189 of 2,039 patients (9.3%) treated with heparin, and in 189 of 2,059 patients (9.2%) treated with bivalirudin (p = not significant). An inverse relation between the risk of abrupt closure and initial ACT measurements was observed in heparin-treated patients: the probability of abrupt vessel closure decreased by 1.3% for every 10-second increase in the initial ACT response to heparin therapy (p = 0.02). Among 903 of 2,039 heparin-treated patients (44%) who received additional heparin for prolonged or complicated procedures, the likelihood of abrupt vessel closure also decreased by 1.1% for every 10-second increase in ACT (p = 0.04). In 2,059 patients treated with bivalirudin, however, no relation between the probability of abrupt vessel closure and the initial ACT measurement was observed (p = 0.88). From the results it was concluded that when heparin is used during coronary angioplasty, the risk of abrupt vessel closure is related to patient responsiveness to anticoagulation therapy. Heparin-resistant patients are more likely to experience abrupt vessel closure than patients who have high ACT values in response to initial therapy. In contrast, when bivalirudin is used during coronary angioplasty, a flat relation between the risk of abrupt vessel closure and ACT values is seen. This suggests that the direct thrombin inhibitor, bivalirudin, provides more even levels of anticoagulation and more predictable levels of risk of abrupt closure than heparin. Measurements of ACT may not be necessary when bivalirudin is used during coronary angioplasty.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Double-Blind Method; Drug Monitoring; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Recurrence; Risk Factors; Whole Blood Coagulation Time

Coagulation activation markers were studied in 148 patients undergoing total hip replacement under recombinant-hirudin (Desirudin, Revasc) prophylaxis with the aim of investigating the efficacy and safety of this anticoagulant compared with heparin in terms of biological effects on coagulation variables and bleeding. Hirudin (10, 15 or 20 mg s.c. b.i.d.) or unfractionated heparin (5000 IU s.c. t.i.d.) was administered immediately before surgery and continued for 8-12 days. Activated partial thromboplastin time (aPTT), prothrombin activation fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT) and D-dimer were measured at baseline and on postoperative days 1,3 and 6, immediately before the morning injection. In comparison with baseline values, heparin had little effect on aPTT whereas the three hirudin doses prolonged aPTT significantly with no differences among the three doses. Moreover, there were no group differences in perioperative or cumulative blood loss or transfusion requirements. F1 + 2 fragment, TAT and D-dimer plasma levels were higher than at baseline during the entire postoperative period, with different trends (F1 + 2 increasing, TAT decreasing, D-dimer increasing, decreasing and then increasing again), but without significant differences among the four treatment groups. Our findings suggest that specific inhibition of thrombin seems a safe and efficacious mode of blocking thrombin activity after hip surgery although it does not prevent thrombin generation.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Coagulation Tests; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fibrinolytic Agents; Hemorrhage; Hemostatics; Hip Prosthesis; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Partial Thromboplastin Time; Recombinant Proteins; Thromboembolism

The likelihood of restenosis is a major limitation of coronary angioplasty. We studied whether hirudin, a highly selective inhibitor of thrombin with irreversible effects, would prevent restenosis after angioplasty. We compared two regimens of recombinant hirudin with heparin.. We randomly assigned 1141 patients with unstable angina who were scheduled for angioplasty to receive one of three treatments: (1) a bolus dose of 10,000 IU of heparin followed by an intravenous infusion of heparin for 24 hours and subcutaneous placebo twice daily for three days (382 patients), (2) a bolus dose of 40 mg of hirudin followed by an intravenous infusion of hirudin for 24 hours and subcutaneous placebo twice daily for three days (381 patients), or (3) the same hirudin regimen except that 40 mg of hirudin was given subcutaneously instead of placebo twice daily for three days (378 patients). The primary end point was event-free survival at seven months. Other end points were early cardiac events (within 96 hours), bleeding and other complications of the study treatment, and angiographic measurements of coronary diameter at six months of follow-up.. At seven months, event-free survival was 67.3 percent in the group receiving heparin, 63.5 percent in the group receiving intravenous hirudin, and 68.0 percent in the group receiving both intravenous and subcutaneous hirudin (P = 0.61). However, the administration of hirudin was associated with a significant reduction in early cardiac events, which occurred in 11.0, 7.9, and 5.6 percent of patients in the respective groups (combined relative risk with hirudin, 0.61; 95 percent confidence interval, 0.41 to 0.90; P = 0.023). The mean minimal luminal diameters in the respective groups on follow-up angiography at six months were 1.54, 1.47, and 1.56 mm (P = 0.08).. Although significantly fewer early cardiac events occurred with hirudin than with heparin, hirudin had no apparent benefit with longer-term follow-up.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Coronary Disease; Disease-Free Survival; Double-Blind Method; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Recurrence; Regression Analysis

Heparin is often administered during and after coronary angioplasty to prevent closure of the dilated vessel. However, ischemic or hemorrhagic complications occur in 5 to 10 percent of treated patients. We studied whether these complications could be prevented when the direct thrombin inhibitor bivalirudin (Hirulog) was used in place of heparin.. We performed a double-blind, randomized trial in 4098 patients undergoing angioplasty for unstable or postinfarction angina. Patients were assigned to receive either heparin or bivalirudin immediately before angioplasty. The primary end point were death in the hospital, myocardial infarction, abrupt vessel closure, or rapid clinical deterioration of cardiac origin.. In the total study group, bivalirudin did not significantly reduce the incidence of the primary end point (11.4 percent, vs. 12.2 percent for heparin) but did result in a lower incidence of bleeding (3.8 percent vs. 9.8 percent, P < 0.001). In the prospectively stratified subgroup of 704 patients with postinfarction angina, bivalirudin therapy resulted in a lower incidence of the primary end point (9.1 percent vs. 14.2 percent, P = 0.04) and a lower incidence of bleeding (3.0 percent vs. 11.1 percent, P < 0.001), but in a similar cumulative rate of death, myocardial infarction, and repeated revascularization in the six months after angioplasty (20.5 percent vs. 25.1 percent, P = 0.17).. Bivalirudin was at least as effective as high-dose heparin in preventing ischemic complications in patients who underwent angioplasty for unstable angina, and it carried a lower risk of bleeding. Bivalirudin, as compared with heparin, reduced the risk of immediate ischemic complications in patients with postinfarction angina, but this difference was no longer apparent after six months.

Topics: Aged; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Double-Blind Method; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Serine Proteinase Inhibitors

Hirudin is an anticoagulant originally extracted from the leech Hirudo medicinalis. Using recombinant DNA technology a new compound, recombinant desulphato hirudin CGP 39393 has now been produced. The aim of this study was to determine the maximum tolerated dose in patients undergoing elective hip replacement. This open safety trial represents, to our knowledge, the first experience of recombinant hirudin in orthopedic patients. In this study 48 patients undergoing primary total hip replacement were included and the safety of subcutaneous injections of 10, 15, 20 and 40 mg CGP 39393 twice daily, was evaluated. Prophylaxis was started immediately pre-operatively and continued for 8-10 days. A mandatory bilateral phlebography was performed at the end of the prophylactic treatment period and a clinical follow-up was done 6 weeks after surgery. A major bleeding event occurred in the first 3 patients receiving 40 mg CGP 39393 b.i.d. and the prophylaxis regimen at this dosage level was therefore discontinued. Median values of total blood loss and requirements of blood transfusion in the patients receiving 10-20 mg CGP 39393 were similar to those reported in previous studies on total hip replacement performed at the same centre, using other prophylactic drugs. Deep vein thrombosis (DVT) was confirmed by phlebography in 5 out of 12 patients in the 10 mg group (41.7%, 95% confidence limits [CL]: 15.2-72.3%), 1 out of 11 patients in the 15 mg group (9.1%, CL: 0.23-41.3%) and 2 out of 20 patients in the 20 mg group (10.0%, CL: 1.2-31.7%) during the prophylaxis period. CGP 39393 was safe and well tolerated, when administered as subcutaneous injections of 10-20 mg twice daily. The dose level of 40 mg CGP 39393 twice daily resulted in serious disturbance of the hemostasis in patients after hip prosthesis surgery.

Topics: Adult; Aged; Aged, 80 and over; Blood Loss, Surgical; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Hemorrhage; Hip Prosthesis; Hirudin Therapy; Hirudins; Humans; Injections, Subcutaneous; Male; Middle Aged; Partial Thromboplastin Time; Postoperative Complications; Recombinant Proteins; Risk Factors; Safety; Thrombin; Thromboembolism

The Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A trial compared the efficacy and safety of intravenous hirudin with heparin as adjunctive therapy to thrombolysis and aspirin in patients with acute myocardial infarction. The primary safety end point was the occurrence of major hemorrhage or anaphylaxis.. Based on experience in phase II trials, TIMI 9A used a hirudin bolus of 0.6 mg/kg followed by a fixed-dose 96-hour infusion of 0.2 mg/kg per hour. A modified weight-adjusted heparin regimen was used (5000-U bolus and infusion of 1000 U/h for patients < 80 kg or 1300 U/h for patients > or = 80 kg) with titration to a target activated partial thromboplastin time (aPTT) of 60 to 90 seconds. Because rates of hemorrhage in both treatment arms were higher than expected, randomization was suspended in TIMI 9A after 757 patients had been enrolled. Intracranial hemorrhage occurred in 1.7% of patients treated with hirudin and 1.9% of those treated with heparin (P = NS). Major spontaneous hemorrhage at a nonintracranial site occurred more frequently in hirudin--than in heparin-treated patients (7.0% versus 3.0%; P = .02), whereas major hemorrhage at instrumented sites was similar (5.2% in both hirudin and heparin groups). Patients who developed a major hemorrhage were older (P < .001) and had higher aPTT values, especially in the first 12 hours after thrombolysis (P = .001).. The rate of major spontaneous hemorrhage for both heparin and hirudin in TIMI 9A was higher than that seen in TIMI 5, TIMI 6, and GUSTO 1. This was possibly a result of high levels of anticoagulation at the doses of heparin and hirudin used, low previous estimates of the hemorrhage risk at the doses of hirudin used in TIMI 9A due to the relatively small number of patients receiving that dose in earlier studies, and enrollment of patients at higher risk of hemorrhage. Because a prolonged aPTT was associated with an increased risk of major hemorrhage in both heparin- and hirudin-treated patients, it now appears important to monitor aPTT on a regular basis when using either antithrombin to identify those patients who require downward adjustment of the infusion. TIMI 9B has therefore been configured with a lower hirudin bolus (0.1 mg/kg) and infusion (0.1 mg/kg per hour) and lower heparin infusion (1000 U/h without weight adjustment). Infusions of both antithrombins will be titrated to a target aPTT of 55 to 85 seconds.

Topics: Aged; Aspirin; Double-Blind Method; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Thrombin; Thrombolytic Therapy

Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction.. Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin (70 IU/kg body wt bolus and 15 IU.kg-1.h-1) or hirudin (0.4 mg/kg body wt bolus and 0.15 mg.kg-1.h-1) infused over 48 to 72 hours and adjusted to an activated partial thromboplastin time of 2 to 3.5 times baseline values. In a pilot phase, 1000 patients receiving front-loaded alteplase for thrombolysis were to be recruited by 93 German centers. After enrollment of 302 patients, the trial was stopped after an increased rate of intracranial bleeding was observed in the hirudin group (5 of 148, 3.4%) compared with the heparin group (0 of 154). The overall stroke rate was 3.4% in the hirudin group and 1.3% in the heparin group. Other major bleeding occurred in five versus three patients and ventricular rupture occurred in three versus one patient in the hirudin and heparin groups, respectively. There were 19 in-hospital deaths, with 13 of them from the hirudin group.. Although the number of patients was too small for a definite benefit-risk assessment, at the dosage tested, hirudin in combination with front-loaded alteplase and aspirin may be associated with an increased rate of intracranial hemorrhage. Our findings are consistent with the observations of the GUSTO-II and TIMI-9 trials, where higher doses of another recombinant hirudin were used. Therefore, the therapeutic range of hirudin as an adjunct to thrombolysis may be smaller than previously thought, and reappraisal of dose finding should be considered.

Topics: Adult; Aged; Cerebrovascular Disorders; Double-Blind Method; Female; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Partial Thromboplastin Time; Pilot Projects; Prospective Studies; Recombinant Proteins; Survival Analysis; Thrombolytic Therapy

Enhanced thrombin activity has been associated with acute and long-term complications following balloon angioplasty (percutaneous transluminal coronary angioplasty (PTCA). We evaluated, in a 2-to-1 randomized, double-blind trial, the effects of recombinant hirudin, CGP 39 393, relative to unfractionated sodium heparin on periprocedural events, bleeding, early angiographic outcome, and coagulation in 113 patients with stable angina undergoing PTCA.. Prior to PTCA, 20 mg CGP 39 393 was administered as a bolus, followed by continuous infusion at a rate of 0.16 mg.kg-1 x h-1, or 10,000 IU sodium heparin was administered as a bolus and continued at a rate of 12 IU.kg-1 x h-1 for 24 hours. Infusion was adjusted to activated partial thromboplastin time (APTT) levels. ST segment was monitored for 24 hours, and angiograms were analyzed with quantitative technique (QCA). In 74 CGP 39 393- and 39 heparin-treated patients, 132 lesions were dilated. Myocardial infarction and/or emergency coronary bypass surgery occurred in 1 (1.4%) CGP 39 393 patient compared with 4 (10.3%) heparin patients (relative risk, 7.6; 95% confidence interval, 0.9, 65.6). At 24 hours, complete perfusion was present in 91% heparin and 100% CGP 39 393 patients. Significant ST segment displacement was found in 11% of heparin versus 4% of CGP 39 393 subjects. Bleeding occurred only at the puncture site in 4 CGP 39 393-treated patients. QCA did not reveal significant differences between the groups. APTT values were more often in the target range and more stable in CGP 39 393 patients. Levels of thrombin-antithrombin III complexes, prothrombin fragment F1+2, and fibrinopeptide A indicated that CGP 39 393 was an effective inhibitor of thrombin activity.. CGP 39 393 can safely be administered to patients undergoing elective PTCA for stable anginal symptoms and may have a more favorable anticoagulant profile than heparin.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Blood Coagulation; Coronary Angiography; Densitometry; Double-Blind Method; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

Since the inception of coronary angioplasty, heparin with or without aspirin has been routinely given intraprocedurally to avoid coronary thrombotic complications. Recently, the direct thrombin inhibitor hirulog has been demonstrated to inactivate clot-bound thrombin. The present study was a multicenter dose escalation of hirulog to determine its appropriate dose and feasibility as the sole anticoagulant during coronary angioplasty.. At 11 participating centers, 291 patients undergoing elective coronary angioplasty and pretreated with 325 mg aspirin daily were enrolled in sequential groups of intravenously administered hirulog instead of heparin as follows: group 1: bolus, 0.15 mg/kg; infusion, 0.6 mg.kg-1.hr-1 (54 patients); group 2: bolus, 0.25 mg/kg; infusion, 1.0 mg.kg-1.hr-1 (53 patients); group 3: bolus, 0.35 mg/kg; infusion, 1.4 mg.kg-1.hr-1 (44 patients); group 4: bolus, 0.45 mg/kg; infusion, 1.8 mg.kg-1.hr-1 (74 patients); and group 5: bolus, 0.55 mg/kg; infusion, 2.2 mg.kg-1.hr-1 (54 patients). The hirulog infusion was maintained for 4 hours; the primary end point was abrupt vessel closure within 24 hours of the initiation of the procedure. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) were serially monitored. Abrupt vessel closure occurred in 18 patients (6.2%). By intention to treat, the abrupt closure event rate for groups 1-3 was 11.3% compared with 3.9% in groups 4 and 5 (p = 0.052). There were no significant bleeding complications except for one patient in group 1, who received a two-unit transfusion. A dose-response curve of both ACTs and aPTTs was noted; no coronary thrombotic closures occurred in the small number of patients with ACT > 300 seconds.. The present study documents for the first time that it is possible to perform coronary angioplasty with an anticoagulant other than heparin in aspirin-pretreated patients. Hirulog was associated with a rapid onset, dose-dependent anticoagulant effect, minimal bleeding complications, and at doses of 1.8-2.2 mg/kg, a rate of 3.9% for abrupt vessel closure.

Topics: Adolescent; Adult; Aged; Amino Acid Sequence; Angioplasty, Balloon, Coronary; Antithrombins; Blood Coagulation; Drug Administration Schedule; Feasibility Studies; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Molecular Sequence Data; Partial Thromboplastin Time; Peptide Fragments; Recombinant Proteins; Time Factors; Vascular Patency

Impella 5.5 (Abiomed; Danvers, MA) (IMP5) is a commonly used, surgically implanted, tMCS device that requires systemic anticoagulation and purge solution to avoid pump failure. To avoid heparin-induced thrombocytopenia (HIT) from unfractionated heparin (UFH) use, our program has explored the utility of bivalirudin (BIV) for systemic anticoagulation and sodium bicarbonate-dextrose purge solution (SBPS) in IMP5.5.. This single center, retrospective study included 34 patients supported on IMP5.5 with BIV based AC and SBPS between December 1st 2020 to December 1st 2021.The efficacy and safety end points were incidence of development of HIT, Tissue Plasminogen Activator (tPA) use for suspected pump thrombosis, stroke, and device failure as well as clinically significant bleeding.. The median duration of IMP5.5 support was 9.8 days (IQR: 6-15). Most patients were bridged to HTX (58%) followed by recovery (27%) and LVAD implantation (15%). Patients were therapeutic on bivalirudin for 64% of their IMP5.5 support. One patient (2.9%) suffered from ischemic stroke and 26.5% (9) patients developed clinically significant bleeding. tPA was administered to 7(21%) patients. One patient in the entire cohort developed HIT.. Our experience supports the use of systemic BIV and SBPS as a method to avoid heparin exposure in a patient population predisposed to the development of HIT.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Sodium Bicarbonate; Thrombocytopenia; Tissue Plasminogen Activator; Treatment Outcome

Patients with diabetes and coronary artery disease have a higher risk of bleeding and thrombotic events. However, data on the safety and efficacy of bivalirudin in these patients undergoing elective percutaneous coronary intervention (PCI) are lacking.. 1152 patients undergoing elective PCI anticoagulated with bivalirudin and 10,250 patients anticoagulated with unfractionated heparin (UFH) (with or without glycoprotein IIb/IIIa inhibitors [GPI]) were performed propensity-score matching method. The thrombotic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The bleeding endpoint was according to the Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding.. Finally, 376 (bivalirudin group) and 878 (UFH group) patients with type 2 diabetes (T2D) were enrolled. After one-year follow-up, there were 130 (10.4%) MACCE and 27 (2.2%) bleeding events occurred. Multivariate COX regression analysis showed no significant difference for MACCE between bivalirudin group and UFH group (P > 0.05). Further analysis showed that there was a reduction in the risk of myocardial infarction (MI) between two groups (Hazard ratio [HR] = 0.199, 95% confidence interval [CI]: 0.047-0.845, P = 0.029), but not in the risk of death, revascularization, stent thrombosis or stroke (all P > 0.05). As for BARC 2, 3 or 5 bleeding, no significant difference was found between two groups (P > 0.05).. Although diabetes is considered a high-risk factor for poor prognosis, compared with UFH (with or without GPI), bivalirudin did not increase the risk of MACCE and even decreased the risk of MI in patients with T2D undergoing elective PCI, while the risk of bleeding was similar between two groups.

Topics: Anticoagulants; Diabetes Mellitus, Type 2; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P<0.05). Thus, bivalirudin presented a better safety profile than heparin among Chinese STEMI patients undergoing PCI.

Topics: Anticoagulants; Antithrombins; East Asian People; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Retrospective Studies; ST Elevation Myocardial Infarction; Treatment Outcome

This study describes the use of bivalirudin in children on extracorporeal membrane oxygenation (ECMO). Pediatric patients receiving bivalirudin were compared to patients receiving heparin as the anticoagulant on ECMO. Data was collected for children under 18 years of age supported by ECMO from January 2016 to December 2019. Data collected included demographics, diagnosis, ECMO indication, type, and duration, indication for bivalirudin use, dose range, activated partial thromboplastin time (aPTT) levels, minor and major bleeding, hemolysis, and mortality. Forty pediatric patients received ECMO; eight received bivalirudin primarily for anticoagulation. The median age was 4 months (IQR 0.5, 92) in the heparin cohort, 0.6 months (IQR 0.0, 80.0) in the primary bivalirudin cohort. The indication for ECMO was respiratory in 5 patients (18%) in the heparin group versus 6 (75%) in the primary bivalirudin group, cardiac in 18 (67%) in heparin versus 1 (12.5%) in primary bivalirudin, and extracorporeal-cardiopulmonary resuscitation (E-CPR) in 4 (15%) in heparin versus 1 (12.5%) in primary bivalirudin. Bivalirudin was the initial anticoagulant for eight patients (66.6%) while three (25%) were switched due to concern for heparin-induced thrombocytopenia (HIT) and one (8%) for heparin resistance. The median time to achieve therapeutic aPTT was 14.5 hours compared to 12 hours in the heparin group. Sixty-five percent of aPTT values in the bivalirudin and 44% of values in the heparin group were in the therapeutic range in the first 7 days. Patients with primary bivalirudin use had significantly lower dose requirement at 12 (p = 0.003), 36 (p = 0.007), and 48 (p = 0.0002) hours compared to patients with secondary use of bivalirudin. One patient (12.5%) had major bleeding, and two patients (25%) required circuit change in the primary bivalirudin cohort. Bivalirudin may provide stable and successful anticoagulation in children. Further large, multicenter studies are needed to confirm these findings.

Topics: Anticoagulants; Child; Child, Preschool; Extracorporeal Membrane Oxygenation; Hemorrhage; Heparin; Hirudins; Humans; Infant; Peptide Fragments; Recombinant Proteins; Retrospective Studies

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs . 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs . 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs . 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH.

Topics: Adult; Anticoagulants; Antithrombins; Extracorporeal Membrane Oxygenation; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombosis; Treatment Outcome

To assess the effectiveness and safety of bivalirudin compared with heparin monotherapy in elderly patients undergoing percutaneous coronary intervention (PCI).. Bivalirudin is recommended for periprocedural use in patients undergoing PCI who are of high bleeding risk. However, its safe and efficacious use in elderly patients, a typical high bleeding risk cohort, in real world practice is yet to be reported.. In this single center, real-world observational study, 4736 consecutive elderly patients who underwent PCI were enrolled. Of these, 1240 were treated with bivalirudin and 3496 with heparin according to the periprocedural anticoagulation strategies of PCI. The primary outcome was 12-month net adverse clinical events (NACE) defined as a composite of cardiac death, myocardial infarction, stroke, revascularization, or any bleeding. Propensity score matching (PSM) was used to balance baseline characteristics between groups.. After PSM, bivalirudin was found to be associated with lower rates of NACE (19.1% vs. 24.7%, p = 0.002), cardiac death (2.7% vs. 4.3%, p = 0.038), and any bleeding (10.0% vs. 12.9%, p = 0.023) compared to heparin monotherapy. No differences were found in the incidences of myocardial infarction, stroke, revascularization, stent thrombosis (0.1% vs. 0.1%, p = 1.000), and major bleedings (0.5% vs. 0.5%, p = 1.000) between the two patient groups.. In this real-world observational study, periprocedural use of bivalirudin in elderly patients who underwent PCI was associated with less cardiac death and any bleeding compared to heparin monotherapy, without increased risk of stent thrombosis.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Death; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Stroke; Thrombosis; Treatment Outcome

The present study aimed to comprehensively investigate the occurrence and risk factors of adverse events (AEs) or adverse drug reactions (ADRs) (especially for thrombocytopenia and bleeding) in Chinese female patients receiving bivalirudin during percutaneous coronary intervention (PCI).. A total of 918 female patients from 27 Chinese medical centers took bivalirudin as anticoagulant for PCI were enrolled in this prospective, multi-center, intensive monitoring study. Safety data (AEs, ADRs, thrombocytopenia and bleeding) were collected from admission to 72 h post bivalirudin administration; then, patients were followed up at the 30. One hundred and twenty (13.1%) patients occurred AEs, among which 7 (0.8%) cases experienced severe AEs, and 2 (0.2%) cases died. Besides, 40 (4.4%) patients occurred bivalirudin-related ADRs, in which 3 (0.3%) cases experienced severe ADRs, but 0 (0.0%) cases died. It was of note that 27 (2.9%) and 13 (1.4%) patients experienced thrombocytopenia and bleeding, respectively. Subsequent multivariate analyses observed that: clinical presentation of spontaneous coronary artery dissection (SCAD) (odds ratio (OR) = 3.191, P = 0.004), CRUSADE high risk (OR = 2.075, P = 0.031), multiple culprit vessel (OR = 2.328, P = 0.019) independently correlated with higher risk of bivalirudin-related ADRs; clinical presentation of SCAD (OR = 4.388, P = 0.002) and multiple culprit vessel (OR = 2.974, P = 0.010) independently linked with raised thrombocytopenia risk; history of diabetes mellitus (OR = 5.227, P = 0.007) and CRUSADE high risk (OR = 4.475, P = 0.016) were independent factor related to elevated bleeding risk.. Bivalirudin is well tolerated with low ADRs, thrombocytopenia and bleeding incidences in Chinese female patients undergoing PCI.

Topics: Aged; Antithrombins; China; Coronary Artery Disease; Female; Hemorrhage; Hirudins; Humans; Incidence; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Risk Assessment; Risk Factors; Sex Factors; Thrombocytopenia; Time Factors; Treatment Outcome

To compare heparin-based anticoagulation and bivalirudin-based anticoagulation within the context of critically ill patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.. An observational study.. At the intensive care unit of a university hospital.. Critically ill patients with a SARS-CoV-2 infection receiving full anticoagulation with heparin or bivalirudin.. Twenty-three patients received full anticoagulation with bivalirudin and 60 with heparin. Despite patients in the bivalirudin group having higher mortality risk scores (SAPS II 60 ± 16 v 39 ±7, p < 0.001) and a higher need for extracorporeal support compared to the heparin group, hospital mortality was comparable (57% v 45, p = 0.3). No difference in thromboembolic complications was observed, and bleeding events were more frequent in patients treated with bivalirudin (65% v 40%, p = 0.01). Similar results were confirmed in the subgroup analysis of patients undergoing intravenous anticoagulation; in addition to comparable thrombotic complications occurrence and thrombocytopenia rate, however, no difference in the bleeding rate was observed (65% v 35%, p = 0.08).. Although heparin is the most used anticoagulant in the intensive care setting, bivalirudin-based anticoagulation was safe and effective in a cohort of critically ill patients with SARS-CoV-2. Bivalirudin may be given full consideration as an anticoagulation strategy for critically ill patients with SARS-CoV-2, especially in those with thrombocytopenia and on extracorporeal support.

Topics: Anticoagulants; Antithrombins; COVID-19; Critical Illness; Extracorporeal Membrane Oxygenation; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Recombinant Proteins; Retrospective Studies; SARS-CoV-2; Thrombocytopenia

Recombinant neorudin (EPR-hirudin, EH) was developed through the addition of an EPR (Glu-Pro-Arg) peptide to the amino terminus of hirudin, which can be recognized and cut by coagulation factors XIa (FXIa) and/or Xa (FXa). In this study, the low-bleeding antithrombotic effects of EH were evaluated utilizing experimental models of thrombosis in rabbits and rats to provide a test basis for clinical trials.. The bleeding risks of EH and hirudin were first compared in mice by the tail-clipping method, and then the antithrombotic activity of EH was investigated in a rabbit model of arteriovenous bypass thrombosis and a rat model of thrombotic cerebral infarction.. In mice, intravenous administration of EH at 1.5 mg/kg and 3 mg/kg did not affect the bleeding time compared with normal saline, while the administration of hirudin at 1.5 mg/kg prolonged the bleeding time by over 3 times the administration of normal saline. Furthermore, intravenous administration of EH had a significant dose-dependent inhibitory effect on the formation and development of arteriovenous bypass thrombosis and thrombotic cerebral infarction. Compared with an equimolar dose of hirudin, the antithrombotic effect of EH was similar, while the bleeding side effects were significantly attenuated. Moreover, when the antithrombotic effects were similar, EH had a shorter bleeding time and was associated with less bleeding than low molecular weight heparin (LMWH). EH had a therapeutic effect on thrombotic cerebral infarction without increasing the occurrence of cerebral hemorrhage.. The findings from the preclinical animal models used in this study showed that EH could not only effectively inhibit thrombus formation but also reduce the risk of bleeding.

Topics: Animals; Cerebral Infarction; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Mice; Rabbits; Rats; Recombinant Proteins; Saline Solution; Thrombosis

Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited.. Retrospective cohort study.. Single tertiary-quaternary referral center.. All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020.. Not applicable.. Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange.. Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis.

Topics: Adult; Anticoagulants; Antithrombins; Child; Heart-Assist Devices; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombosis; Treatment Outcome; Young Adult

Unfractionated heparin is the most commonly utilized anticoagulant in extracorporeal membrane oxygenation (ECMO) due to clinician familiarity, ease of reversal, and low cost compared to alternative agents. However, heparin's anticoagulant effect can be unpredictable and its use accompanies a risk of heparin induced thrombocytopenia (HIT). Successful use of bivalirudin as an alternative to heparin in non-HIT ECMO patients has previously been described. However, there is a paucity of data regarding its utilization in patients with confirmed HIT on ECMO.. This single-center retrospective chart review at Cleveland Clinic Main Campus included 12 ECMO patients who were managed with bivalirudin for a new diagnosis of HIT. Descriptive statistical analyses were performed utilizing median with interquartile range and number with percent as appropriate.. Of the 12 patients included, median ECMO duration was 328.5 (218.8-502.1) h and venoarterial ECMO was the most common configuration. No patients experienced the primary outcome of in-circuit thrombosis while on bivalirudin. One patient developed a deep vein thrombosis 22.5 h after switching from heparin to bivalirudin. Major bleeding occurred during bivalirudin therapy in 8 (66.7%) patients.. Overall, our study results suggest that bivalirudin is effective for the management of HIT and did not show evidence of in-circuit thrombosis. A high incidence of major bleeding was observed with bivalirudin use within this study. Clinicians should view bivalirudin as an acceptable agent for the treatment of HIT in the ECMO population, but must consider bleeding risk given the lack of effective reversal agents.

Topics: Anticoagulants; Extracorporeal Membrane Oxygenation; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombocytopenia; Thrombosis

This prospective, multi-center, intensive monitoring study aimed to systematically assess the occurrence of adverse events (AEs) and adverse drug reactions (ADRs), especially thrombocytopenia and bleeding, as well as their risk factors in Chinese ST-segment elevation myocardial infraction (STEMI) patients receiving bivalirudin as anticoagulant for percutaneous coronary intervention (PCI).. In total, 1244 STEMI patients undergoing PCI and receiving bivalirudin as anticoagulant were enrolled in the present study. Safety data were collected from hospital admission to 72 h after bivalirudin administration; in addition, patients were further followed up at the 30th day with safety data collected at that time.. AEs, severe AEs, ADRs and severe ADRs were reported in 224 (18.0%), 15 (1.2%), 49 (3.9%) and 5 (0.4%) patients, respectively. Importantly, 4 (0.3%) patients were submitted to hospitalization and 6 (0.5%) patients died due to AEs, while 1 (0.1%) patient was submitted to hospitalization but no (0.0%) patient died due to ADRs. Meanwhile, thrombocytopenia and bleeding occurred in 24 (1.9%) and 21 (1.7%) patients, respectively. Further multivariate logistic analysis identified several important independent factors related to AEs, ADRs, thrombocytopenia or bleeding, which included history of cardiac surgery and renal function impairment, high CRUSADE risk stratification, elective operation and combination with glycoprotein IIb/IIIa inhibitors. Moreover, 4 multivariate models were constructed based on the above-mentioned factors, which all showed acceptable predictive value for AEs, ADRs, thrombocytopenia and bleeding, respectively.. Bivalirudin is a well-tolerant anticoagulant in Chinese STEMI patients undergoing PCI procedure.

Topics: Anticoagulants; Antithrombins; China; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; ST Elevation Myocardial Infarction; Thrombocytopenia; Treatment Outcome

Optimal anticoagulants for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) are unclear. This retrospective observational study is aimed at evaluating efficacy and safety of bivalirudin versus unfractionated heparin (UFH) monotherapy in patients with DM undergoing PCI.. A total of 3890 diabetic patients receiving PCI in the General Hospital of Northern Theater Command were divided into the bivalirudin group (. After propensity score matching, the bivalirudin group was associated with a lower incidence of NACEs (3.0% vs. 6.0%,. In diabetic patients undergoing PCI, bivalirudin was significantly associated with reduced risks of 30-day NACE and MACCE, mainly driven by the lower rates of bleeding and mortality, compared with heparin monotherapy.

Topics: Anticoagulants; Antithrombins; Diabetes Mellitus; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

There is a paucity of data regarding the use of direct thrombin inhibitors such as bivalirudin for children on extracorporeal life support (ECLS). We sought to compare the outcomes of children on ECLS anticoagulated with bivalirudin versus heparin. Patients transitioned from heparin to bivalirudin were treated as a separate group. A single-institution, retrospective review of all consecutive children (neonate to 18 years) placed on ECLS in the cardiac or pediatric intensive care units was performed (June 2018-December 2019). Data collected included demographics, anticoagulation strategy, number of circuit interventions, blood product use on ECLS, survival to decannulation, and survival to discharge. Fifty-four children were placed on ECLS for a total of 56 runs. Demographics and venovenous versus venoarterial ECLS were similar. The bivalirudin group had longer median duration of support compared to the heparin group--11.0 days [IQR 6.2, 23.1] versus 3.3 days [2.1, 6.2], P < .001. Patients switched from heparin to bivalirudin had a similar duration of support (10.3 days [8.3, 18.3]) as those on bilvalirudin alone. However, there was no difference in red blood cell, fresh frozen plasma, or platelet transfusions. There was no difference in the number of circuit interventions, survival to decannulation or discharge. The freedom to first circuit intervention was longer with bivalirudin compared to heparin. Our data suggest that even with longer pediatric ECLS runs on bivalirudin, there were no differences in the outcomes between the heparin and bivalirudin groups, with longer freedom from first circuit intervention with bivalirudin. While this is the largest reported series comparing children on ECLS anticoagulated with heparin versus bivalirudin, larger studies are needed to determine the optimal anticoagulation strategy for this diverse and complicated group of children.

Topics: Adolescent; Anticoagulants; Blood Coagulation; Child; Child, Preschool; Critical Illness; Drug Substitution; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Heparin; Hirudins; Hospitals, High-Volume; Humans; Infant; Intensive Care Units, Pediatric; Male; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Stroke; Thrombosis

A recent heparin shortage related to an outbreak of African Swine Flu in China led to substantial increase in the use of direct thrombin inhibitors (DTI) as an alternative. We evaluated the safety and efficacy of DTIs by assessing the anticoagulation assays within the initial 48 h of therapy comparing before and during shortage. A retrospective evaluation of bivalirudin and argatroban was conducted at a single center before (May 24, 2018 through August 25, 2019) and during heparin shortage (August 26, 2019 through February 20, 2020). The primary outcome was time to first therapeutic activated partial thromboplastin time (aPTT). Secondary outcomes included the percentage of time in therapeutic aPTT range, in-hospital mortality, incidence of recurrent thrombosis, and hemorrhagic events. Of the 204 patients included in the study, 95 patients [bivalirudin (n = 35), argatroban (n = 60)] were included in the pre-shortage cohort and 109 patients [bivalirudin (n = 68), argatroban (n = 41)] were during shortage. No significant difference was observed in the time to first therapeutic aPTT pre- and during shortage (8.9 h ± 10.8 vs 8.8 h ± 10.2, P = 0.62). Compared to pre-shortage cohort, a greater percentage of time was spent in therapeutic aPTT range within the initial 48 h (32% (0-50) vs. 41.6% (0-63), P = 0.04) during shortage without statistically significant differences in the rates of in-hospital mortality, thrombosis, or bleeding. While the optimal DTI protocol is still be determined, the protocols presented in this study allowed for wide-spread utilization of DTIs during a critical heparin shortage without compromising patient safety and effectiveness, likely reflective of the enhancement of DTI protocols, clinician education, and multidisciplinary collaboration and guidance from pharmacy and hematology.

Topics: Anticoagulants; Antithrombins; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Partial Thromboplastin Time; Pipecolic Acids; Recombinant Proteins; Retrospective Studies

Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support.. Retrospective cohort study.. Single-center, cardiothoracic ICU.. Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020.. IV bivalirudin or IV unfractionated heparin.. Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001.. Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.

Topics: Adult; Anticoagulants; Antithrombins; Erythrocyte Transfusion; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Plasma; Platelet Transfusion; Recombinant Proteins; Retrospective Studies; Thrombosis

The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to the population of all screened patients with fulfilled inclusion criteria in regard to mortality at 30 and 180 days.. The standardized difference in the mean propensity score for trial inclusion between trial population and the screened not-enrolled with fulfilled inclusion criteria was calculated as a metric of similarity. Propensity scores were then used in an inverse-probability weighted Cox regression analysis using the trial population only to estimate the difference in mortality as it would have been had the trial included all screened patients with fulfilled inclusion criteria. Patients who were very likely to be included were weighted down and those who had a very low probability of being in the trial were weighted up.. The propensity score difference was 0.61. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis (hazard ratio 1.11, 95% confidence interval (0.73, 1.68)) at 30 days or 180 days (hazard ratio 0.98, 95% confidence interval (0.70, 1.36)).. The propensity score difference demonstrated that the screened not-enrolled with fulfilled inclusion criteria and trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality. From this, we conclude that the VALIDATE results may be generalized to the screened not-enrolled with fulfilled inclusion criteria.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

This study sought to investigate the clinical outcomes of patients with and without peripheral artery disease (PAD) in the BRAVO-3 trial with respect to the effect of bivalirudin versus unfractionated heparin (UFH).. PAD is found frequently in patients undergoing transcatheter aortic valve replacement (TAVR) and is reported to confer an increased risk of adverse events. It is unknown whether patients with and without PAD may demonstrate a differential response to bivalirudin versus UFH.. BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or cerebrovascular accidents (CVA). Net adverse cardiovascular events (NACE) were a composite of major bleeding or MACE.. The total cohort included 119 patients with PAD. Vascular complications occurred significantly more frequently in patients with PAD both in-hospital (25.2 vs. 16.7%; OR 1.68) and at 30 days (29.4 vs. 17.3%; OR 1.99). No significant differences were observed regarding mortality, NACE, MACE, major bleeding or CVA with bivalirudin versus UFH among patients with or without PAD. In patients with PAD, bivalirudin was associated with an increased risk of minor vascular complications at 30 days.. Patients with PAD undergoing transfemoral TAVR did not exhibit an increased risk of any major adverse events, according to the procedural anticoagulant randomization. However, patients treated with Bivalirudin had significantly higher rates of minor vascular complications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Catheterization, Peripheral; Cerebrovascular Disorders; Europe; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Male; Myocardial Infarction; North America; Peptide Fragments; Peripheral Arterial Disease; Punctures; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome

The efficacy and safety of continued bivalirudin infusion after percutaneous coronary intervention (PCI) remains uncertain. We sought to investigate the association between post-PCI bivalirudin infusion and the risk of net adverse clinical events (NACE) at 30 days.. In the GLOBAL LEADERS study, all patients who received bivalirudin during PCI were categorized according to the use of bivalirudin infusion after the procedure. The primary endpoint of the present analysis was NACE [a composite of all-cause death, any stroke, any myocardial infarction, all revascularization, and bleeding assessed according to the Bleeding Academic Research Consortium (BARC) criteria Type 3 or 5] at 30 days. The key safety endpoint was BARC Type 3 or 5 bleeding and definite stent thrombosis. Of 15 968 patients, 13 870 underwent PCI with the use of bivalirudin. In total, 7148 patients received continued bivalirudin infusion after procedure, while 6722 patients received standard care. After propensity score covariate adjustment, the risk of NACE did not significantly differ between two treatments after PCI [continued bivalirudin infusion vs. no bivalirudin infusion: 3.2% vs. 3.1%, adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) 0.99-1.84, P = 0.06] nor the BARC Type 3 or 5 bleeding (0.7% vs. 0.7%, aHR 0.89, 95% CI 0.44-1.79; P = 0.743) and definite stent thrombosis (0.5% vs. 0.3%, aHR 1.71, 95% CI 0.77-3.81, P = 0.189). However, continued bivalirudin infusion was associated with an increased risk of NACE and definite stent thrombosis in ST-elevation myocardial infarction (STEMI) patients.. In an all-comers population undergoing PCI, there was no significant difference in the risk of NACE at 30 days between continued bivalirudin infusion vs. no bivalirudin infusion after procedure but continued bivalirudin infusion was associated with a higher risk of NACE in STEMI patients when compared with no infusion.

Topics: Aged; Antithrombins; Coronary Artery Disease; Coronary Thrombosis; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stents; Time Factors; Treatment Outcome

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anemia; Angina, Unstable; Anticoagulants; Antithrombins; Aspirin; Cause of Death; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug-Eluting Stents; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Hemorrhage; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Stents; Ticagrelor; Urologic Diseases

A study is presented on the effectiveness and safety of various anticoagulants used in patients of an older age group with acute coronary syndrome during percutaneous coronary interventions. Bivalirudin was shown to be highly effective in comparison with unfractionated heparin and monafram in relation to the amount of bleeding that occurs in the postoperative period and adverse cardiovascular complications.. Представлено исследование по изучению эффективности и безопасности различных антикоагулянтов, используемых у больных старшей возрастной группы с острым коронарным синдром при чрескожных коронарных вмешательствах. Показана высокая эффективность бивалирудина по сравнению с нефракционированным гепарином и монафрамом в отношении числа кровотечений, возникающих в послеоперационном периоде, и неблагоприятных сердечно-сосудистых осложнений.

Topics: Acute Coronary Syndrome; Aged; Antibodies, Monoclonal; Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

Procedural anticoagulation with bivalirudin (BIV), trans-radial intervention (TRI), and use of a vascular closure device (VCD) are thought to mitigate percutaneous coronary intervention (PCI)-related bleeding. We compared the impact of these bleeding avoidance strategies (BAS) for PCIs stratified by bleeding risk.. We performed a retrospective cohort analysis of PCIs from 18 facilities within one health care system from 2009Q3 to 2017Q4. Bleeding risk was assessed per the National Cardiovascular Data Registry CathPCI bleeding model, with procedures stratified into 6 categories (first, second, third quartiles, 75th-90th, 90th-97.5th, and top 2.5th percentiles). Regression models were used to assess the impact of BAS on bleeding outcome.. Of 74 953 PCIs, 9.4% used no BAS, 12.0% used BIV alone, 20.8% used TRI alone, 26.8% used VCD alone, 5.4% used TRI+BIV, and 25.6% used VCD+BIV. The crude bleeding rate was 4.4% overall. Only 2 comparisons showed significant trends across all risk strata: VCD+BIV versus no BAS, odds ratio (95% CI) range: first quartile, 0.36 (0.18-0.72) to top 2.5th percentile, 0.50 (0.32-0.78); TRI versus no BAS, odds ratio (95% CI) range: first quartile, 0.15 (0.06-0.38) to top 2.5th percentile, 0.49 (0.28-0.86). TRI had lower odds of bleeding compared with BIV for all risk strata except the top 2.5th percentile. Addition of BIV to TRI did not change the odds of bleeding for any risk strata. Factors potentially limiting use of TRI (renal failure, shock, cardiac arrest, and mechanical circulatory support) were present in ≤10% of procedures below the 90th percentile.. Among individual BAS, only TRI had consistently lower odds of bleeding across all risk strata. Factors potentially limiting TRI were found infrequently in procedures below the 90th percentile of bleeding risk. For transfemoral PCI, VCD+BIV had lower odds of bleeding compared with no BAS across all risk strata.

Topics: Aged; Antithrombins; Catheterization, Peripheral; Female; Hemorrhage; Hemostatic Techniques; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Punctures; Radial Artery; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; United States; Vascular Closure Devices

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged <19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.

Topics: Adolescent; Antithrombins; Arginine; Child; Child, Preschool; Female; Heart-Assist Devices; Hemorrhage; Hirudins; Humans; Infant; Male; North America; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Retrospective Studies; Stroke; Sulfonamides; Thrombosis; Treatment Outcome

This study aimed to assess the efficacy and safety of bivalirudin compared with UFH in high bleeding risk patients with ACS undergoing PCI in current practice.. All consecutive high-bleeding-risk patients who underwent PCI for ACS at the First Affiliated Hospital of Zhengzhou University from January to September 2019 were retrospectively analyzed. The 30-day primary outcome was a composite of major bleeding, myocardial infarction, all-cause death, or stroke (net adverse clinical events [NACEs]), and the secondary outcomes at 30 days included a composite of myocardial infarction, stoke, or all-cause death (major adverse cardiovascular events [MACEs]), each component of the primary outcome, target vessel revascularization (TVR) and stent thrombosis (ST). Besides, we assessed angina-related health status at 30 days, the length of hospital stay, and hospitalization costs. A logistic regression model was used to adjust for baseline differences. Consistency of the treatment effect of bivalirudin for NACEs and MACEs compared with UFH was evaluated in 15 prespecified subgroups.. From January to September 2019, 823 patients (361 treated with bivalirudin and 462 treated with UFH) were enrolled in the study. GPIs, novel P2Y. The treatment of bivalirudin showed better efficacy and safety as compared to UFH among patients with ACS undergoing PCI at high risk of bleeding in contemporary practice.

Topics: Acute Coronary Syndrome; Anticoagulants; Disease Management; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Practice Patterns, Physicians'; Recombinant Proteins; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome

Bivalirudin, a direct thrombin inhibitor, is a treatment option for the management of heparin-induced thrombocytopenia (HIT) and other coagulation disorders. To date, no published studies have identified patients at risk for or the consequence of subtherapeutic bivalirudin therapy.. The primary objective was to identify factors associated with failure to achieve early therapeutic anticoagulation (ETA) with bivalirudin, defined as achievement of two consecutive therapeutic activated partial thromboplastin times (aPTTs) within 24 hours. Secondary objectives included evaluating whether failure to achieve ETA was a risk factor for clinical outcomes of interest including thromboembolism, hemorrhage, and mortality.. This was a retrospective cohort study. Patients between the ages of 18 and 89 years treated with bivalirudin for 24 hours or longer were identified and classified as either achieving or failing to achieve ETA.. Nonadherence to the dosing protocol (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.07-2.71) and creatinine clearance (CrCl) of 60 ml/min or greater (OR 2.99, 95% CI 1.12-7.97) were significantly associated with failure to achieve ETA in univariate analyses. Conversely, increasing age (OR 0.98, 95% CI 0.97-0.99) was significantly associated with achievement of ETA. Failure to achieve ETA was associated with a 4-fold increase in the odds of thromboembolism.. Younger age, normal renal function, and nonadherence to the dosing protocol when targeting therapeutic anticoagulation is associated with increased risk of failure to achieve ETA. This confers an elevated risk of thromboembolism when using bivalirudin for the management of HIT or other coagulation disorders.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anthropology, Medical; Antithrombins; Cohort Studies; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Partial Thromboplastin Time; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Risk Factors; Thrombocytopenia; Thromboembolism; Treatment Failure; Young Adult

Topics: Adrenal Gland Diseases; Aged; Anticoagulants; Atrial Fibrillation; Diabetic Angiopathies; Hemorrhage; Heparin; Hirudins; Humans; Hydrocortisone; Hypotension; Male; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombocytopenia; Treatment Outcome; Vasoconstrictor Agents

A pharmacoinvasive strategy for ST-segment elevation myocardial infarction (STEMI) management combines the use of fibrinolysis with the routine transfer to coronary angiography, with percutaneous coronary intervention (PCI) if needed. This method reduces the risk of major adverse cardiovascular event (MACE) compared with fibrinolysis alone; however, it is associated with higher bleeding risk. We sought to assess the bivalirudin compared with unfractionated heparin (UFH) used during PCI as part of a pharmacoinvasive strategy.. We identified consecutive patients referred to the University of Ottawa Heart Institute between April 2009 and May 2011 as part of a pharmacoinvasive strategy for STEMI. The primary efficacy outcome was MACE, defined as a composite of death, reinfarction, or stroke during index hospitalization. The primary safety outcome was TIMI bleeding.. We identified 200 patients meeting inclusion criteria: 123 patients (61.5%) in the bivalirudin group and 77 patients (37.5%) in the UFH group. Median fibrinolysis to balloon time was 324 minutes in the bivalirudin group and 226 minutes in the UFH group (P<.001). Initial TIMI grade 3 flow was higher in the bivalirudin group vs the UFH group, but there was no difference in the rates post PCI. MACE rates were 4.9% vs 7.8% (P=.40) and TIMI bleeding rates were 7.3% vs 11.7% (P=.29) in patients treated with bivalirudin vs UFH, respectively.. The periprocedural use of bivalirudin vs UFH was associated with similar rates of MACE and bleeding. Given the expense of bivalirudin and lack of demonstrable clinical superiority, UFH remains the first-line periprocedural anticoagulant in a pharmacoinvasive strategy.

Topics: Coronary Angiography; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Outcome and Process Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Perioperative Care; Postoperative Complications; Recombinant Proteins; Risk Adjustment; ST Elevation Myocardial Infarction

Extracorporeal membrane oxygenation mandates balancing the risk of thromboembolic complications with bleeding. We aimed to evaluate pragmatic anticoagulation regimens during extracorporeal membrane oxygenation and compare thromboembolic and bleeding outcomes.. This retrospective, single-center study reviewed patients on venovenous or venoarterial extracorporeal membrane oxygenation for a minimum of 24 hours over a 5-year period. The primary outcome was composite thromboembolic events per day of extracorporeal membrane oxygenation. Secondary outcomes included composite bleeding complications, percent of measured activated partial thromboplastin times in goal range, and comparing events with therapeutic anticoagulation for the majority of the extracorporeal membrane oxygenation run (>50% of time on extracorporeal membrane oxygenation) versus non-therapeutic anticoagulation (therapeutic anticoagulation <50% of time).. For the primary analysis, 100 patients received heparin, 10 received bivalirudin, and 43 were transitioned between heparin and bivalirudin. No significant differences were identified comparing the heparin group to the bivalirudin (RR = 0.427, p = 0.156) or transitioned group (RR = 1.274, p = 0.325). There were no differences in the rate of bleeding events when comparing the heparin group to the bivalirudin (RR = 0.626, p = 0.250) or transitioned group (RR = 0.742, p = 0.116). An increased number of adjustments to the anticoagulants was associated with a statistically higher rate of bleeding events per day (p = 0.006).. There were no differences in thromboembolic or bleeding events when comparing different anticoagulant regimens. Adjustments to the anticoagulants are more likely to occur when bleeding is observed. Due to variability in anticoagulation, there is a need to standardize anticoagulation with extracorporeal membrane oxygenation.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thromboembolism

The best combination of access site and anticoagulant used during primary percutaneous coronary intervention (PCI) in patients presenting with ST segment elevation myocardial infarction is not known.. We conducted a retrospective cohort study of all patients >18 years of age who underwent primary PCI in 2 large regional ST segment elevation myocardial infarction centers in Massachusetts between 2012 and 2014. The cohort was divided into 3 groups: bival/fem, hep/rad, or off-protocol, based on anticoagulation and access used. We used multiple logistic regression model to compare major cardiovascular events-major adverse cardiovascular events (MACE) and bleeding complications between the 2 on-protocol groups (bival/fem and hep/rad).. Of the 1074 patients in this study, there were 443 (41%), 501 (47%), and 130 (12%) patients in bival/fem, hep/rad, and off-protocol groups, respectively. There were significantly higher number of cardiogenic shock patients in the bival/fem compared to the hep/rad group (6.5% vs. 3.0%, P < 0.001). There was a trend toward reduced MACE in the hep/rad group compared to bival/fem (2.8 % vs. 5.1%, P = 0.068). When cardiogenic shock patients are excluded, there is no significant difference in mortality rates (bival/fem: 2.7% vs. hep/rad: 1.0%, P = 0.07) or bleeding complications between the groups (hep/rad: 4.5% vs. bival/fem: 2.1%, P = 0.06).. In patients undergoing primary PCI, there was a trend toward reduced inpatient MACE with the use of heparin and radial access compared with bivalirudin with femoral access. In patients without cardiogenic shock, there is no significant difference in mortality or bleeding rates between the 2 groups.

Topics: Antithrombins; Catheterization, Peripheral; Female; Femoral Artery; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Massachusetts; Middle Aged; Outcome and Process Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Radial Artery; Recombinant Proteins; Retrospective Studies; Shock, Cardiogenic; ST Elevation Myocardial Infarction

Acute heparin-induced thrombocytopenia (HIT) patients present a myriad of anticoagulation management challenges, in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy. We describe the tailored post-CPB management of refractory bleeding in a 65-year-old infective endocarditis, acute HIT patient with renal failure who underwent urgent aortic valve replacement and mitral valve repair with bivalirudin anticoagulation. A management approach that entailed a combination of continuous venovenous haemofiltration (CVVH), 4-Factor prothrombin complex concentrate (PCC) (Beriplex), recombinant factor VIIa (rFactor VIIa) and desmopressin (DDAVP) were consecutively used post-operatively in theatre. Based on this case study experience, two modifications to institutional protocols are recommended. The first is the use of CVVH in theatre to eliminate bivalirudin in renal failure patients or in patients where bivalirudin elimination is prolonged. Secondly, a 'rescue therapy/intervention' algorithm for the swift identification of refractory bleeding post-CPB is also recommended. Rescue therapy agents, such as a 4-Factor PCCs and rFactor VIIa, should be incorporated into the protocol after a robust evidence-based search and agreement with the haematologist. The aim of these recommendations is to reduce the risk of bleeding associated with bivalirudin use for inexperienced institutions and experienced institutions alike, until larger randomized, controlled studies provide more in-depth knowledge to expand our clinical practice.

Topics: Acute Disease; Aged; Anticoagulants; Aortic Valve; Blood Coagulation Factors; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Factor VIIa; Hemorrhage; Hemostatics; Heparin; Hirudins; Humans; Male; Mitral Valve; Peptide Fragments; Recombinant Proteins; Renal Insufficiency; Thrombocytopenia

Patients with end-stage renal disease undergoing percutaneous coronary intervention (PCI) have largely been excluded from trials of antithrombotic therapies leaving little data to guide agent choice in this population.. The National Cardiovascular Data Registry CathPCI Registry was used to identify patients with end-stage renal disease undergoing PCI who received monotherapy with either bivalirudin or unfractionated heparin (UFH) (n=71 675). In hospital bleeding and mortality were compared and adjusted using the CathPCI Registry logistic regression models with generalized estimating equations with UFH as the reference. Bivalirudin was used in 51.3% of patients versus 48.7% for UFH. The use of bivalirudin decreased over time, and in 2014, UFH became the most frequently used. Patients receiving UFH were more likely to have an acute coronary syndrome presentation (37.8% versus 27.4%) or have cardiogenic shock (3.74% versus 1.98%). The observed rates for in hospital bleeding (7.0% versus 9.5%; adjusted odds ratio,0.82; 95% confidence interval, 0.76-0.87) and mortality (2.6% versus 4.2%; adjusted odds ratio, 0.87; 95% confidence interval, 0.78-0.97) were lower for patients receiving bivalirudin compared with those receiving UFH.. In patients with end-stage renal disease undergoing PCI, bivalirudin and UFH were used with similar frequency although the patterns of use changed over the enrollment period. Patients with end-stage renal disease undergoing PCI had a lower adjusted risk of in hospital outcomes with bivalirudin; however, given the observational nature of this analysis, a randomized trial is warranted.

Topics: Aged; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Risk Factors; Time Factors; Treatment Outcome

Hirudin is a potent thrombin inhibitor but its antithrombotic properties are offset by bleeding side-effects. Because hirudin's N-terminus must engage thrombin's active site for effective inhibition, fusing a cleavable peptide at this site may improve hirudin's risk/benefit ratio as a therapeutic agent. Previously we engineered a plasmin cleavage site (C) between human serum albumin (HSA) and hirudin variant 3 (HV3) in fusion protein HSACHV3. Because coagulation factor XI (FXI) is more involved in thrombosis than hemostasis, we hypothesized that making HV3 activity FXIa-dependent would also improve HV3's potential therapeutic profile. We combined albumin fusion for half-life extension of hirudin with positioning of an FXIa cleavage site N-terminal to HV3, and assessed in vitro and in vivo properties of this novel protein.. FXIa cleavage site EPR was employed. Fusion protein EPR-HV3HSA but not HSAEPR-HV3 was activated by FXIa in vitro. FVIIa, FXa, FXIIa, or plasmin failed to activate EPR-HV3HSA. FXIa-cleavable EPR-HV3HSA reduced the time to occlusion of ferric chloride-treated murine arteries and reduced fibrin deposition in murine endotoxemia; noncleavable mycHV3HSA was without effect. EPR-HV3HSA elicited less blood loss than constitutively active HV3HSA in murine liver laceration or tail transection but extended bleeding time to the same extent. EPR-HV3HSA was partially activated in citrated human or murine plasma to a greater extent than HSACHV3.. Releasing the N-terminal block to HV3 activity using FXIa was an effective way to limit hirudin's bleeding side-effects, but plasma instability of the exposed EPR blocking peptide rendered it less useful than previously described plasmin-activatable HSACHV3.

Topics: Albumins; Animals; Factor XIa; Hemorrhage; Hirudins; Mice; Models, Animal; Recombinant Fusion Proteins; Thrombosis

Topics: Anticoagulants; Antithrombins; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Treatment Outcome

The aim of this study was to compare bivalirudin with heparin as anticoagulant agents in patients with ST-segment elevation myocardial infarction treated with radial primary percutaneous coronary intervention (PCI).. Recent studies in which PCI was performed predominantly via radial access did not show bivalirudin to be superior to heparin.. Outcomes were compared in patients with STEMI included in the National Cardiovascular Data Registry CathPCI database from 2009 to 2015 who underwent primary PCI via radial access and who were anticoagulated with bivalirudin or heparin.. The sample included 67,368 patients, of whom 29,660 received bivalirudin and 37,708 received heparin. The 2 groups of patients did not differ significantly in their mean age or percentage of men. The unadjusted comparison showed no significant difference in the rate of the composite endpoint of death, myocardial infarction, or stroke (4.6% vs. 4.7%; p = 0.47) and a significantly higher rate of acute stent thrombosis (1.00% vs. 0.60%; p < 0.001) with bivalirudin compared with heparin. After adjusting for multiple variables, including a propensity score reflecting the probability of receiving bivalirudin, the odds ratio of the composite endpoint of death, myocardial infarction, or stroke for bivalirudin versus heparin was 0.95 (95% confidence interval: 0.87 to 1.05; p = 0.152), and the odds ratio for acute stent thrombosis was 2.11 (95% confidence interval: 1.73 to 2.57) for bivalirudin versus heparin. Major bleeding rates were not significantly different.. In patients undergoing primary PCI via transradial access anticoagulated with bivalirudin or heparin, there was no difference in the composite endpoint of death, myocardial infarction, or stroke.

Topics: Aged; Anticoagulants; Chi-Square Distribution; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Propensity Score; Radial Artery; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Time Factors; Treatment Outcome; United States

Bivalirudin is a reasonable choice during transradial PCI for acute MI when bleeding risk is high and clopidogrel or cangrelor is used Heparin is reasonable during transradial PCI when bleeding risk is low and high-intensity antiplatelet therapy is used Future studies are required to define the utility of post-PCI bivalirudin infusions.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

Thrombolysis is still used when primary angioplasty is delayed for a long time, but 25%-30% of patients require rescue angioplasty (RA). There are no established recommendations for antithrombotic management in RA. This registry analyzes regimens for antithrombotic management.. A retrospective, multicenter, observational registry of consecutive patients treated with RA at 8 hospitals. All variables were collected and follow-up took place at 6 months.. The study included 417 patients. Antithrombotic therapy in RA was: no additional drugs 22.3%, unfractionated heparin (UFH) 36.6%, abciximab 15.5%, abciximab plus UFH 10.5%, bivalirudin 5.7%, enoxaparin 4.3%, and others 4.7%. Outcomes at 6 months were: mortality 9.1%, infarction 3.3%, definite or probable stent thrombosis 4.3%, revascularization 1.9%, and stroke 0.5%. Mortality was related to cardiogenic shock, age > 75 years, and anterior location. The stent thrombosis rate was highest with bivalirudin (12.5% at 6 months). The incidence of bleeding at admission was high (14.8%), but most cases were not severe (82% BARC ≤2). Variables independently associated with bleeding were: femoral access (OR 3.30; 95% CI 1.3-8.3: p = 0.004) and post-RA abciximab infusion (OR 2.26; 95% CI 1.02-5: p = 0.04).. Antithrombotic treatment regimens in RA vary greatly, predominant strategies consisting of no additional drugs or UFH 70 U/kg. No regimen proved predictive of mortality, but bivalirudin was related to more stent thrombosis. There was a high incidence of bleeding, associated with post-RA abciximab infusion and femoral access.

Topics: Abciximab; Aged; Antibodies, Monoclonal; Chi-Square Distribution; Coronary Thrombosis; Drug Administration Schedule; Enoxaparin; Female; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; Immunoglobulin Fab Fragments; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Spain; Thrombolytic Therapy; Time Factors; Treatment Failure

The debate regarding the choice of heparin or bivalirudin as the preferred anticoagulant in PCI is still ongoing Nonrandomized registry data are severely limited for comparative analyses and should therefore always be interpreted with caution Clinicians should resist simplistic data interpretations or populist cries relating to cost, but rather focus on valid benefit:risk analyses for their clinical decision making.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

BACKGROUND Diffuse alveolar hemorrhage (DAH) is a rare but potentially fatal complication of anticoagulant or antiplatelet therapy. Bivalirudin is a specific and reversible direct thrombin inhibitor (DTI). CASE REPORT We report a case of severe DAH, possibly related to bivalirudin use, in a 61-year-old patient undergoing coronary intervention. The patient had presented with an out-of-hospital cardiac arrest due to acute ST elevation myocardial infarction (STEMI). During the coronary intervention, shortly after receiving bivalirudin, the patient started having frank bleeding from the endotracheal tube and developed hemodynamic compromise. Despite aggressive intervention and intensive care, the patient died. CONCLUSIONS At this time, to our knowledge, there have been no reports of DAH associated with the use of bivalirudin.

Topics: Antithrombins; Fatal Outcome; Hemorrhage; Hirudins; Humans; Lung Diseases; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Peptide Fragments; Percutaneous Coronary Intervention; Pulmonary Alveoli; Recombinant Proteins; ST Elevation Myocardial Infarction

Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label.. The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT.. In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score ≥4 points), and received treatment with ≥1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings.. Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux.. Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and argatroban is contraindicated in patients with impaired liver function, and activated partial thromboplastin time confounding may interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II; NCT01304238).

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin; Heparitin Sulfate; Hirudins; Hospital Mortality; Hospitalization; Humans; Male; Necrosis; Off-Label Use; Partial Thromboplastin Time; Patient Safety; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Registries; Retrospective Studies; Sulfonamides; Thrombocytopenia; Thromboembolism; Treatment Outcome

Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR.. BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women.. The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH.. There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve; Aortic Valve Stenosis; Cardiac Catheterization; Europe; Female; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin; Hirudins; Humans; Male; Multicenter Studies as Topic; Myocardial Infarction; North America; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Factors; Sex Factors; Stroke; Time Factors; Treatment Outcome

This study aimed to compare the association of access site complications and the use of unfractionated heparin versus bivalirudin during subinguinal peripheral vascular intervention.. Compared to unfractionated heparin, bivalirudin has been associated with fewer bleeding complications in patients undergoing percutaneous coronary intervention but more ischemic events. The safety and efficacy of direct thrombin inhibitors in peripheral vascular interventions is not well defined.. We compared the incidence of in-hospital access site complications and discharge status among patients in the multicenter, prospective Vascular Quality Initiative registry who underwent peripheral vascular intervention between August 2007 and January 2014 using bivalirudin or unfractionated heparin. Propensity score matching was used to obtain a balanced cohort of 1,524 patients in each treatment group.. Patients treated with bivalirudin had a significantly lower incidence of access site hematomas (2.4% vs. 3.9%, P = 0.018), shorter post-procedural hospitalization (1.0 vs. 1.2 days, P < 0.001) and lower rates of discharge to a nursing home or rehabilitation center rather than home (7.61% vs. 9.73%, P = 0.034) when compared with unfractionated heparin-treated patients. The incidence of in-hospital access site occlusion, distal embolization, and mortality did not differ significantly between groups.. Patients who received bivalirudin had lower rates of access site hematoma, shorter length of stay, and improved discharge status compared with unfractionated heparin during hospitalization for peripheral vascular intervention. Randomized comparisons of these agents are needed to confirm these findings. © 2016 Wiley Periodicals, Inc.

Topics: Aged; Anticoagulants; Antithrombins; Canada; Catheterization, Peripheral; Chi-Square Distribution; Female; Hematoma; Hemorrhage; Heparin; Hirudins; Humans; Length of Stay; Logistic Models; Male; Odds Ratio; Patient Discharge; Peptide Fragments; Propensity Score; Punctures; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Treatment Outcome; United States

The aim of the study was to compare outcomes in unfractionated heparin (UFH) and bivalirudin-treated patients undergoing primary percutaneous coronary intervention (PPCI).. This observational study contained 20,612 PPCI patients treated with either UFH monotherapy or bivalirudin with or without concomitant UFH. Patients with oral anticoagulant or glycoprotein IIb/IIIa inhibitor (GPI) treatment were excluded. The primary outcome measure was definite early stent thrombosis (ST) that occurred at low and similar rates in UFH only and bivalirudin-treated patients: 0.9% vs. 0.8% (adjusted hazard ratio [HR] 1.08, 95% confidence interval [CI]: 0.7-1.65). All-cause death at 30 days occurred in 6.9% vs. 5.4% of patients (adjusted HR 1.23, 95% CI: 1.05-1.44) and within 365 days in 12.1% vs. 8.9% (adjusted HR 1.34, 95% CI: 1.19-1.52) in the two groups, respectively. The incidence of major bleeding within 30 days was 0.8% vs. 0.6% (adjusted HR 1.54, 95% CI: 0.97-2.45). The incidence of reinfarction within 365 days and stroke within 30 days was similar between groups.. In this large, nationwide observational study we found low and similar rates of early ST in UFH only and bivalirudin-treated patients undergoing primary PCI. Mortality was higher in UFH compared with bivalirudin-treated patients.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

This study aimed to evaluate the effect of prolonged full-dose bivalirudin infusion in real-world population with ST-elevation myocardial infarction (STEMI).. Subgroup data as well as meta-analysis from randomized clinical trials have shown the potency of postprocedural full-dose infusion (1.75 mg/kg/h) of bivalirudin on attenuating acute stent thrombosis (ST) after primary percutaneous coronary intervention (PCI).. In this multicenter retrospective observational study, 2047 consecutive STEMI patients treated with bivalirudin during primary PCI were enrolled in 65 Chinese centers between July 2013 and May 2016. The primary outcome was acute ST defined as ARC definite/probable within 24 hours after the index procedure, and the secondary endpoints included total ST, major adverse cardiac or cerebral events (MACCE, defined as death, reinfarction, stroke, and target vessel revascularization), and any bleeding at 30 days.. Among 2047 STEMI patients, 1123 (54.9%) were treated with postprocedural bivalirudin full-dose infusion (median 120 minutes) while the other 924 (45.1%) received low-dose (0.25 mg/kg/h) or null postprocedural infusion. A total of three acute ST (0.3%) occurred in STEMI patients with none or low-dose prolonged infusion of bivalirudin, but none was observed in those treated with post-PCI full-dose infusion (0.3% vs 0.0%, P=.092). Outcomes on MACCE (2.1% vs 2.7%, P=.402) and total bleeding (2.1% vs 1.4%, P=.217) at 30 days showed no significant difference between the two groups, and no subacute ST was observed.. Post-PCI full-dose bivalirudin infusion is safe and has a trend to protect against acute ST in STEMI patients undergoing primary PCI in real-world settings.

Topics: Aged; Antithrombins; China; Coronary Angiography; Coronary Thrombosis; Female; Hemorrhage; Hirudins; Humans; Infusions, Parenteral; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Recurrence; Retrospective Studies; Risk Factors; ST Elevation Myocardial Infarction; Stents; Time Factors; Treatment Outcome

Dialysis patients are at a higher risk of bleeding after percutaneous coronary intervention (PCI); however, due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. We sought to evaluate the comparative safety and effectiveness of bivalirudin monotherapy versus unfractionated heparin (UFH) monotherapy in dialysis patients undergoing PCI.. We included dialysis patients who underwent PCI in a multicenter registry between January 2010 and September 2015 at 47 Michigan hospitals. We compared in-hospital outcomes between bivalirudin versus UFH; excluding those treated with glycoprotein IIb/IIIa inhibitors. Optimal full matching was used to account for the nonrandom use of these drugs.. Of 177,963 patients who underwent PCI, 4,303 (2.4%) were on dialysis. Among those, 1,257 (29.2%) received bivalirudin monotherapy and 2,112 (49.1%) received UFH monotherapy. Patients treated with bivalirudin had fewer comorbidities. After matching, there were no significant differences in outcomes between those who received bivalirudin versus UFH: bleeding (adjusted odds ratio: 0.67; 95% confidence interval: 0.41-1.07; P = 0.093); major bleeding (0.81; 0.19-3.50; P = 0.77); transfusion (1.01; 0.77-1.33; P = 0.96); repeat PCI (0.57; 0.14-2.24; P = 0.42); stent thrombosis (0.56; 0.05-5.83; P = 0.63); and death (0.84; 0.46-1.51; P = 0.55).. We found no significant differences in in-hospital outcomes between bivalirudin and UFH monotherapy among dialysis patients undergoing PCI. Randomized clinical trials are needed to determine the optimal anticoagulant regimen for this population. © 2017 Wiley Periodicals, Inc.

Topics: Aged; Anticoagulants; Antithrombins; Blue Cross Blue Shield Insurance Plans; Comparative Effectiveness Research; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Logistic Models; Male; Michigan; Middle Aged; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Propensity Score; Recombinant Proteins; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Stents; Thrombosis; Time Factors; Treatment Outcome

Currently the majority of coronary and peripheral interventions are performed with an overnight stay. This increases the cost and does not reduce logistic constraints on hospital resources. We hypothesised that by combining bivalirudin with vascular closure devices we can safely discharge patients on the same day after percutaneous coronary intervention (PCI) and percutaneous transluminal angioplasty (PTA) without increasing their risk of bleeding.. To evaluate the safety and the feasibility of same-day discharge after PCI and PTA using bivalirudin and vascular closure devices.. This is a retrospective analysis of 833 consecutive patients who underwent percutaneous procedures in our centre between January 2007 and February 2010. The population was divided into interventional and diagnostic arms. All interventions were done with use of bivalirudin for anticoagulation and vascular closure devices for achieving haemostasis. Haemostasis in the diagnostic cohort was achieved with standard manual compression. The mean time of observation was 30 days. The mean age of patients was 64.3 years. The primary endpoint was any bleeding event meeting GUSTO criteria. The secondary endpoints included local vascular complications, major adverse cardiac and cerebrovascular events, time to ambulation and discharge, as well as need for overnight hospitalisation.. In 30-day observation the primary endpoint occurred in 4.0% of patients in the interventional group and in 2.6% of patients in the diagnostic group (p = 0.31). The frequency of local vascular complications was higher in the interventional group although it was not statistically significant (3.1% vs. 2.9%; p = 0.33). Patients from the interventional group were ambulated sooner compared to the diagnostic group (117.5 vs. 131 min; p = 0.003). Time to discharge was 316.4 ± 38.7 min and 214.2 ± 23.4 min for interventional and diagnostic procedures, respectively (p < 0.001).. PCI and PTA in the selected group of patients, with use of bivalirudin and vascular closure devices, do not appear to have increased risk of post-procedural events when compared to diagnostic procedures, and can be done safely without the need for an overnight stay.

Topics: Aged; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Female; Hemorrhage; Hirudins; Hospitalization; Humans; Male; Middle Aged; Patient Discharge; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Vascular Closure Devices

We aimed to construct a predictive model for one-year mortality in patients undergoing invasive coronary evaluation and to examine the impact of bivalirudin on survival according to the level of baseline risk.. Compared to heparin plus GP IIb/IIIa inhibitors (HEP/GPI), bivalirudin decreases bleeding complications in a range of clinical presentations. The impact of preprocedural risk assessment on survival and whether this is modified by bivalirudin, has not been investigated in detail.. We examined patient-level data from the REPLACE-2, ACUITY, and HORIZONS-AMI trials (n = 18,819) to construct a risk-adjusted mortality model using baseline clinical variables.. One-year mortality occurred in 287 patients (3.1%) assigned to bivalirudin and 336 patients (3.6%) assigned to HEP/GPI (HR 0.85; 95% CI, 0.73-1.00; P = 0.048). Using 11 highly significant predictors of mortality, we developed an integer-risk score to classify patients into risk tertiles. High-risk patients had a rate of 1-year mortality over 9-fold greater than low-risk patients. Consequently, the absolute mortality reduction attributed to bivalirudin was more marked in high-risk patients: 3.1% (-0.8% to 7.0%) in the overall cohort, 4.8% (0.5% to 9.2%) in the PCI cohort (P-interaction versus intermediate and low risk categories, 0.09 and P = 0.02, respectively).. In patients undergoing invasive coronary evaluation, 1-year mortality can be predicted using baseline variables. Bivalirudin treatment (versus HEP/GPI) conferred a survival benefit.

Topics: Aged; Angina, Stable; Angina, Unstable; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

To observe the efficacy and safety of bivalirudin use in Chinese patients with coronary heart disease (CHD) during the peri-percutaneous coronary intervention(PCI) period.. A total of 3 271 patients who underwent PCI and received periprocedural bivalirudin treatment between July 2013 and October 2015 from 88 centers of China were involved in this study. The primary outcome was 30-day net adverse clinical events (NACE a composite of major adverse cardiac or cerebral events (MACE, all-cause death, reinfarction, urgent target vessel revascularization, or stroke) or bleeding), the secondary outcome was stent thrombosis at 30 days.. The mean age of enrolled patients was (65.12±12.44) years old, 27.4%(889/3 244) of them were female. Percent of stable coronary disease (SCD), non-ST segment elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) was 5.0%(162/3 248), 44.6%(1 450/3 248) and 50.4%(1 636/3 248) respectively. Radial access was performed in 89.5% (2 879/3 271) patients, and 9.7% (316/3 271) and 34.1% (1 115/3 271) patients also received ticagrelor and tirofiban medication. 69.3% (2 266/3 271) patients received post-procedural bivalirudin infusion, in which 46.3% (1 050/2 266) was treated at PCI-does, with a median duration of 2.5(1.0, 4.0) h. During the 30-day follow-up, NACE occurred in 3.45% (103/2 988) patients, the incidence of MACE, death was 2.17% (65/2 994) and 1.03% (31/3 017), respectively and bleeding events were recorded in 1.37% (41/2 996) patients. Four cases (0.13%) of stent thrombosis (3 acute stent thrombosis) were recorded.. Peri-PCI Bivalirudin use is safe and related with low bleeding risk in Chinese CHD patients.

Topics: Aged; China; Coronary Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Retrospective Studies; Stroke; Tirofiban; Tyrosine

The association of bleeding avoidance strategy (BAS) (consisting of a combination of radial access, bivalirudin [rather than heparin +/- glycoprotein GPIIb/IIIa antagonists], and/or vascular closure devices after femoral access) with bleeding and in-hospital outcomes has not been evaluated among elderly patients undergoing percutaneous coronary interventions (PCI).. We studied BAS use, bleeding and in-hospital mortality among 121,635 patients categorized by age (<50, 50-59, 60-69, 70-79, and ≥80years) undergoing PCI from the BMC2 registry (1/2010-12/2013).. The use of BAS decreased marginally with age and despite improved utilization over time, remained lower among the elderly. BAS was used in a much lower risk cohort among all age groups. Nonetheless, compared with no BAS, the use of this strategy was associated with lower bleeding (adjusted OR 0.984, 95% CI 0.980-0.985) and in-hospital mortality (adjusted OR 0.996, 95% CI 0.994-0.997) among all age-groups. Similar relative reduction in the risk of bleeding was observed among all age groups with BAS use with lowest risk (thus greatest absolute risk reduction given their highest risk for bleeding) for the oldest cohort.. BAS use decreased with age among patients undergoing PCI despite its association with lower in-hospital mortality. Although overall utilization improved over time, it still remained lower in the elderly cohort, a group likely to benefit most from it. These data identified an opportunity to design strategies to improve BAS use particularly among high-risk elderly patients undergoing PCI so as to decrease bleeding and reduce related adverse events and costs.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antithrombins; Blue Cross Blue Shield Insurance Plans; Catheterization, Peripheral; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Female; Femoral Artery; Hemorrhage; Hemostatic Techniques; Hirudins; Hospital Mortality; Humans; Logistic Models; Male; Michigan; Middle Aged; Multivariate Analysis; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Punctures; Recombinant Proteins; Registries; Risk Factors; Time Factors; Treatment Outcome

The aim of this study was to explore whether the use of bleeding avoidance strategies (BAS) explains variability in hospital-level bleeding following percutaneous coronary intervention.. Prior studies have reported that bleeding rates following percutaneous coronary intervention vary markedly among hospitals, but the extent to which use of BAS explains this variation is unknown.. Using the American College of Cardiology National Cardiovascular Data Registry's CathPCI Registry, estimated hospital-level bleeding rates from 2,459,686 procedures at 1,358 sites were determined. A series of models were fit to estimate random-effect variance, adjusting for patient risk (using the validated CathPCI bleeding risk model, C statistic = 0.77) and various combinations of BAS (transradial access, bivalirudin, vascular closure device use). The rate of any BAS use was also estimated for each hospital, and the association between percentage BAS use and predicted bleeding rates was determined.. In total, 125,361 bleeding events (5.1%) were observed; patients experiencing bleeding events had lower rates of radial access (5.0% vs. 11.2%; p < 0.001), bivalirudin therapy (43.8% vs. 59.4%), and vascular closure device use (32.9% vs. 42.4%, p < 0.001) than those without bleeding. There was significant variation in bleeding rates across hospitals (median 5.0%; interquartile range [IQR]: 2.7% to 6.6%), which persisted after incorporating patient-level risk (median 5.1%; IQR: 4.0% to 4.4%). Patient factors accounted for 20% of the overall hospital-level variation, and radial access plus bivalirudin use accounted for an additional 7.8% of the overall hospital-level variation. The median hospital rate of any BAS use was 86.6% (IQR: 72.5% to 94.1%). A significant decrease in observed hospital-level bleeding was seen in hospitals above the median in BAS use (adjusted odds ratio: 0.90; 95% confidence interval: 0.88 to 0.93).. A modest proportion of the variation in hospitals' rates of bleeding following percutaneous coronary intervention is attributable to differential use of BAS. Further analyses are required to determine the remaining approximately 70% causes of variation in percutaneous coronary intervention bleeding seen among hospitals.

Topics: Aged; Antithrombins; Cardiac Catheterization; Catheterization, Peripheral; Chi-Square Distribution; Female; Healthcare Disparities; Hemorrhage; Hirudins; Hospitals; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Practice Patterns, Physicians'; Process Assessment, Health Care; Radial Artery; Recombinant Proteins; Registries; Risk Assessment; Risk Factors; Treatment Outcome; United States; Vascular Closure Devices

Transition from bivalirudin to long-term warfarin therapy is often difficult to execute due to bivalirudin prolongation of the international normalized ratio (INR), and literature to help guide this transition is extremely limited.. To assess the transition from bivalirudin to warfarin after implementation of an institution-wide transition protocol.. In this retrospective quasiexperimental study, adult patients receiving bivalirudin directly followed by warfarin for nonprocedural systemic anticoagulation were evaluated to determine the frequency of successful transition to warfarin. Participants were compared before (preprotocol) and after (postprotocol) the implementation of the transition protocol.. A total of 39 patients met inclusion criteria and were included in the analysis (preprotocol = 19; postprotocol = 20). The percentage of patients achieving a successful transition was significantly higher in the postprotocol group compared with the preprotocol group (80.0% vs 42.1%, P = 0.015). Bleeding events were similar between the 2 groups (23.1% vs 16.7%, P = 0.689). Withholding of warfarin doses or the use of anticoagulant reversal agents or blood transfusions for supratherapeutic INR levels, surgical procedures, or drop in hemoglobin was numerically lower in the postprotocol group compared with the preprotocol group (16.7% vs 46.2%, P = 0.202).. Implementation of a simplistic bivalirudin-warfarin transition protocol significantly increased the frequency of therapeutic INR results on bivalirudin discontinuation. Additionally, patients treated according to this protocol were less likely to have warfarin doses withheld or require reversal agents. Larger studies testing this transition strategy are warranted.

Topics: Adult; Aged; Anticoagulants; Female; Hemorrhage; Hirudins; Humans; International Normalized Ratio; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombocytopenia; Transitional Care; Warfarin

During the pre-procedural (medication) phase, the use of bivalirudin monotherapy is associated with the lowest rate of bleeding in patients with Non-ST elevation myocardial infarction (Non-STEMI) undergoing an early invasive strategy. Monotherapy with either bivalirudin or unfractionated heparin (UFH) appear interchangeable in this setting. The use of GPI upstream with either drug should be discouraged due to an increased risk of bleeding and net adverse events. The use of low dose aspirin plus potent P2Y12 inhibitors followed by a transradial approach with implantation of drug-eluting coronary stents with fluorinated polymers represents an strategy that may help limit perioperative ischemic and hemorrhagic complications in these individuals.

Topics: Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

Intracoronary thrombus is a common finding in acute coronary syndromes and often correlates with adverse prognosis and complications during percutaneous coronary interventions (PCIs). Bivalirudin, a direct thrombin inhibitor, is one of the recommended antithrombotic treatments for PCI in ST-elevation myocardial infarction (STEMI). The intracoronary administration of a bivalirudin loading dose, even if off-label, offers theoretical advantages over the standard intravenous route, providing a very high drug concentration in the infarct-related artery without increasing the total dose of the drug administered. After the description in case reports of such an approach, a larger scale experience was recently reported in a large cohort of patients with STEMI treated during primary PCI with a bivalirudin intracoronary loading dose followed by the standard intravenous maintenance infusion. As a control group, a propensity score-matched cohort of patients undergoing primary PCI treated with intravenous bivalirudin in the same institution was selected. Compared with the intravenous bolus, the intracoronary administration of bivalirudin was associated with improved ST-segment resolution, lower post-procedural peak CK-MB levels, and better Thrombolysis in Myocardial Infarction (TIMI) frame count values, without difference in bleeding rates. Thus, this new promising antithrombotic strategy, based on the intracoronary administration of a bivalirudin loading dose during primary PCI, appeared safe, improved myocardial reperfusion, and mitigated enzymatic myocardial infarct size compared with the standard intravenous protocol. Randomized trials are warranted to confirm these results and evaluate the possible long-term clinical benefits.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Electrocardiography; Hemorrhage; Hirudins; Humans; Injections, Intravenous; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Thrombosis

The purpose of this study was to describe temporal trends and determine the comparative effectiveness of bivalirudin versus unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).. Several clinical trials have compared the safety and effectiveness of bivalirudin versus UFH during PCI for STEMI, but results have been conflicting.. Trends in anticoagulant use were examined among 513,775 PCIs for STEMI from July 2009 through December 2014 within the National Cardiovascular Data Registry CathPCI Registry. We conducted an instrumental variable analysis comparing bivalirudin with UFH, using operator preference for bivalirudin as the instrument. We used a test of mediation to determine the extent to which differences in outcomes between anticoagulants were due to differences in use of glycoprotein IIb/IIIa inhibitors (GPI). Primary outcomes were in-hospital bleeding and mortality.. Bivalirudin use increased from 2009 through 2013, followed by a new decline. GPIs were used in 74.7% of UFH PCIs versus 26.5% of bivalirudin PCIs. In unadjusted analyses, bivalirudin was associated with decreased bleeding (risk difference [RD]: -4.2%; p < 0.001) and mortality (RD: -0.84%; p < 0.001). After instrumental variable analyses, bivalirudin remained associated with less bleeding (RD: -3.75%; p < 0.001), but not mortality (RD: -0.10%; p = 0.280). The higher rate of GPI use with UFH was responsible for more than one-half of bivalrudin's bleeding reduction (GPI-adjusted RD: -1.57%; p < 0.001). Bleeding reductions were negligible for transradial PCI (RD: -0.11%; p = 0.842).. The use of bivalirudin during STEMI has decreased. Bivalirudin was associated with reduced bleeding and no mortality difference. The bleeding reduction with bivalirudin was largely explained by the greater use of GPIs with UFH.

Topics: Aged; Anticoagulants; Antithrombins; Comparative Effectiveness Research; Coronary Thrombosis; Drug Utilization Review; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Risk Factors; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome; United States

Pharmacoinvasive therapy (PIT) is a potential treatment for ST-segment elevation myocardial infarction patients who are not able to achieve primary percutaneous intervention (PCI) within guideline-recommended time limits. The risk for bleeding complications with PIT has not been studied in the setting of routine use of two selected bleeding avoidance strategies (BAS): bivalirudin and vascular closure devices.. We analyzed a contemporary multicenter registry (2009-2013) of consecutive patients undergoing PCI as part of a 10-hospital regional algorithm involving one PCI center and nine transfer centers: PIT for hospitals greater than 60 min (N=140), and primary PCI if less than 60-min travel time to the PCI center (N=346). We compared the risk for Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS) major bleeding among patients undergoing PIT versus primary PCI in the setting of routine use of selected BAS and determined the independent predictors of major bleeding in the entire cohort.. The PIT patients had a median travel time of 103±49 min, were more frequently female, had a higher incidence of renal failure, and had a lower frequency of cardiogenic shock compared with the primary PCI group. BAS were routine and similar in both groups. Rates of death, stroke, and ischemic and major bleeding outcomes were similar between the two groups, and the length of stay was shorter in the PIT group. Multivariate logistic models indicated that two independent predictors of major bleeding were cardiac arrest [odds ratio (OR)=3.89, 95% confidence interval (CI): 1.2-12.1, P=0.02] and bailout glycoprotein IIb/IIIa inhibitor utilization (OR=3.29, 95% CI: 1.1-9.6, P=0.03). The PIT strategy in conjunction with selected BAS did not predict major bleeding (OR=2.1, 95% CI: 0.85-5.44, P=0.11).. Bleeding and ischemia rates were similar between the PIT and primary PCI strategies in the setting of routine use of selected BAS; further study on a broader range of BAS including the radial approach may be warranted. Cardiac arrest and bailout glycoprotein IIb/IIIa inhibitor, but not PIT in conjunction with selected BAS, are independent predictors of bleeding risk in a regional ST-segment elevation myocardial infarction population.

Topics: Aged; Antithrombins; Catchment Area, Health; Equipment Design; Female; Health Services Accessibility; Health Services Needs and Demand; Hemorrhage; Hemostatic Techniques; Hirudins; Humans; Length of Stay; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Transportation of Patients; Treatment Outcome; Vermont

Argatroban is the only commercially available Food and Drug Administration (FDA)-approved anticoagulant for managing heparin-induced thrombocytopenia (HIT). However, bivalirudin may be an attractive alternative.. To assess the efficacy and safety of argatroban and bivalirudin in patients with suspected HIT.. This single-center, retrospective analysis included patients who received argatroban or bivalirudin for at least 24 hours between January 1, 2000, and June 30, 2012. The primary end point assessed anticoagulation goals, specifically time to therapeutic activated partial thromboplastin time (aPTT) goal and percentage of aPTT values within therapeutic range. Secondary end points included new thromboembolic events, bleeding, and mortality.. Of the 68 patients who met the inclusion criteria, 48 received argatroban and 20 received bivalirudin. Baseline characteristics were similar between the 2 groups except for age, percentage of patients with liver dysfunction, aPTT immediately prior to drug initiation, and the serotonin release assay results. The mean ± SD times to reach therapeutic aPTT goal for argatroban and bivalirudin were 14 ± 15 and 7 ± 8 hours, respectively (P = 0.024). The mean ± SD percentage of aPTT values within therapeutic aPTT goal was 69% ± 23% for argatroban and 84% ± 18% for bivalirudin (P = 0.005). Rates of thromboembolic events were similar between the 2 groups, as were the rates of bleeding and all-cause mortality.. Bivalirudin appears to reach therapeutic aPTT goal faster with more aPTT values within therapeutic aPTT goal while achieving similar clinical outcomes. Although not approved by the FDA for managing HIT, bivalirudin may be an attractive alternative anticoagulant.

Topics: Aged; Anticoagulants; Arginine; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Partial Thromboplastin Time; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Retrospective Studies; Sulfonamides; Thrombocytopenia

Topics: Anticoagulants; Blood Platelets; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Patient Selection; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Recurrence; Risk Assessment; Risk Factors; Treatment Outcome

Bivalirudin has historically been considered an attractive anticoagulant during percutaneous coronary intervention (PCI) because of reduced bleeding complications reported by early trials. Bivalirudin use during PCIs has been a subject of controversy because of conflicting data and recent findings.. To evaluate the clinical characteristics of patients receiving bivalirudin to determine if an opportunity to improve use exists based on risk of procedure-related bleeding.. This was a single-center, retrospective, observational study (n = 100) of all adult patients who received bivalirudin during cardiac catheterization at St John Hospital and Medical Center from June to August 2013. The risk of bleeding complications associated with PCI was estimated using a clinical risk algorithm developed from the National Cardiovascular Data Registry (NCDR).. Treatment with bivalirudin was safe and effective. Of the 100 patients who received bivalirudin, only 34% were identified as having a high risk of procedure-related bleeding according to the NCDR clinical risk algorithm. There was no incidence of stent thrombosis noted and only 1 case of provisional glycoprotein IIb/IIIa inhibitor use. No episodes of Thrombolysis in Myocardial Infarction (TIMI) major bleeding were noted in the study population; however, 1 patient met TIMI minor bleeding criteria. Limitations of this study include small sample size and retrospective nature of the study.. Opportunities to establish a more cost-effective use of bivalirudin may exist through implementation of protocols incorporating the NCDR risk assessment model.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Risk; Treatment Outcome

The primary objective of this study is the compare the association between bleeding and the use unfractionated heparin (UFH) versus bivalirudin during percutaneous coronary intervention (PCI).. In patients undergoing PCI, the risk of bleeding with use of bivalirudin compared with UFH in the absence of glycoprotein IIb/IIIa inhibitors is not well defined.. Patients undergoing PCI with either UFH or bivalirudin monotherapy at a single institution between 2007 and 2014 were included (n = 6,143). Propensity score matching was used to adjust for baseline characteristics yielding 2,984 well matched patients (1,492 in each group). The primary endpoint was major non-coronary artery bypass graft (non-CABG) related bleeding as defined by a Bleeding Academic Consortium type 3 or 5. Secondary outcomes included combined major and minor bleeding, in-hospital death, periprocedural myocardial infarction, and recurrent ischemia requiring urgent revascularization (repeat PCI).. In the propensity matched cohort, there was no difference in major bleeding between UFH and bivalirudin monotherapy (1.8% versus 2.4%, P = 0.305). Combined major and minor bleeding was also similar between the two groups (4.3% versus 4.3%, P = 1.0). Likewise, no differences were observed between the bivalirudin and UFH groups in terms of in-hospital death (0.4% versus 0.5%, P = 0.592), periprocedural myocardial infarction (1.5% versus 2.0%, P = 0.332) and repeat PCI (0.7% versus 0.8%, P = 0.669).. Among patients undergoing PCI, there was no significant difference in rate of bleeding between bivalirudin and heparin monotherapy in a real-world setting.

Topics: Aged; Anticoagulants; Antithrombins; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Propensity Score; Recombinant Proteins; Risk Factors; Treatment Outcome

Topics: Anticoagulants; Antithrombins; Coronary Angiography; Drug Therapy, Combination; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Stroke; Treatment Outcome

To estimate periprocedural bleeding risk before elective percutaneous coronary intervention (PCI) by using a point-of-care bleeding risk calculator and to document changes in anticoagulant use and bleeding complications after implementation of use of this calculator.. Prospective observational pilot study with a historical control cohort.. Tertiary care medical center.. The pilot cohort consisted of 100 patients undergoing ad hoc PCI during elective cardiac catheterization procedures between January and May 2013, whose bleeding risk and accompanying PCI anticoagulant recommendations were determined by the use of a pre-PCI point-of-care bleeding risk calculator. The historical control cohort consisted of all patients who underwent elective PCI at the same facility between April 1, 2011, and March 31, 2012, before implementation of use of the bleeding risk calculator.. The pre-PCI bleeding risk calculator distinguished patients in the pilot cohort as high risk (score 12 or higher) or low risk (lower than 12) for bleeding after a PCI procedure. The primary outcome was bivalirudin use in the pilot cohort compared with its use in the historical control cohort. Implementation of the bleeding risk calculator significantly decreased bivalirudin use compared with bivalirudin use in the historical control cohort (87% in the control cohort vs 60% in the pilot cohort, p<0.01). Bivalirudin use remained high in patients at high bleeding risk (82.2% in the pilot cohort vs 87.4% in the control cohort, p=0.3) and its use was decreased in patients at low bleeding risk (41.8% in the pilot cohort vs 87.1% in the control cohort, p<0.01). The incidence of bleeding complications in the pilot cohort was comparable with that in the control cohort (1% vs. 0.4%, p=0.37), although this pilot study was underpowered to potentially detect a significant change in the incidence of bleeding complications.. A simple bleeding risk calculator can substantially reduce overall bivalirudin use by specifically decreasing its use among patients at low bleeding risk while maintaining its use among patients at high bleeding risk. The incidence of bleeding complications remained unchanged despite decreasing bivalirudin use among patients undergoing elective coronary catheterization who were at low risk for bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Glomerular Filtration Rate; Health Care Costs; Hemorrhage; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Pilot Projects; Point-of-Care Systems; Prospective Studies; Recombinant Proteins; Risk Assessment

The Premier Perspective hospital billing database provides a promising data source for studies of inpatient medication use. However, in-hospital recording of confounders is limited, and incorporating linked healthcare claims data available for a subset of the cohort may improve confounding control. We investigated methods capable of adjusting for confounders measured in a subset, including complete case analysis, multiple imputation of missing data, and propensity score (PS) calibration.. Methods were implemented in an example study of adults in Premier undergoing percutaneous coronary intervention (PCI) in 2004-2008 and exposed to either bivalirudin or heparin. In a subset of patients enrolled in UnitedHealth for at least 90 days before hospitalization, additional confounders were assessed from healthcare claims, including comorbidities, prior medication use, and service use intensity. Diagnostics for each method were evaluated, and methods were compared with respect to the estimates and confidence intervals of treatment effects on repeat PCI, bleeding, and in-hospital death.. Of 210,268 patients in the hospital-based cohort, 3240 (1.5 %) had linked healthcare claims. This subset was younger and healthier than the overall study population. The linked subset was too small for complete case evaluation of two of the three outcomes of interest. Multiple imputation and PS calibration did not meaningfully impact treatment effect estimates and associated confidence intervals.. Despite more than 98 % missingness on 24 variables, PS calibration and multiple imputation incorporated confounders from healthcare claims without major increases in estimate uncertainty. Additional research is needed to determine the relative bias of these methods.

Topics: Adult; Aged; Anticoagulants; Confounding Factors, Epidemiologic; Databases, Factual; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Hospitals; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Propensity Score; Recombinant Proteins

Excess dosing of anticoagulant agents has been linked to increased risk of bleeding after percutaneous coronary intervention (PCI) for women compared with men, but these studies have largely included older patients. We sought to determine the prevalence and gender-based differences of excess dosing of anticoagulants including glycoprotein IIb/IIIa inhibitors, bivalirudin, and unfractionated heparin in young patients with acute myocardial infarction who underwent PCI and to examine its association with bleeding. Of 2,076 patients enrolled in the Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients study who underwent PCI, we abstracted doses of unfractionated heparin, bivalirudin, and glycoprotein IIb/IIIa inhibitors administered during PCI from the medical records. At least 47.2% received at least 1 excess dose of an anticoagulant, which did not differ by gender. We used logistic regression to determine the predictors of excess dosing and the association of excess dosing with bleeding. In multivariable analysis, only lower body weight and younger age were significant predictors of excess dosing. Bleeding was higher in young women who received excess dosing versus those who did not (9.3% vs 6.0%, p = 0.03) but was comparable among men (5.2% vs 5.9%, p = 0.69) in univariate analysis. In multivariable analysis, there was a trend to an association between excess dosing and bleeding (odds ratio 1.33, 95% confidence interval 0.92 to 1.91) although not statistically significant. In conclusion, approximately half of the patients received excess dosing of anticoagulant drugs during PCI, which did not vary based on gender. There was a trend toward an association between excess dosing and increased bleeding, although not statistically significant.

Topics: Adult; Age Distribution; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Body Mass Index; Cohort Studies; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Prevalence; Recombinant Proteins; Risk Assessment; Risk Factors; Sex Distribution; Treatment Outcome; United States

Topics: Antithrombins; Blood Coagulation; Coronary Restenosis; Hemorrhage; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation; Postoperative Complications; Recombinant Proteins; Risk Assessment

Bivalirudin and heparin are the major available parenteral anticoagulants for percutaneous coronary intervention (PCI) in ST-segment-elevation myocardial infarction. Even though hard clinical outcomes are comparable with both drugs, bivalirudin appears to be safer (less bleeding events) at the expense of lower short-term efficacy (more acute stent thrombosis events). The selection of anticoagulation during PCI in ST-segment-elevation myocardial infarction should be individualized, taking into account the patient's ischemic and bleeding risk. In patients with increased bleeding risk, bivalirudin might be preferable to heparin, whereas in complex PCI with increased risk for stent thrombosis, heparin is preferable. Further clinical studies are needed to elucidate the role of these drugs in PCI for ST-segment-elevation myocardial infarction in the era of radial approaches, new potent antiplatelet agents and the use of glycoprotein IIb/IIIa inhibitors.

Topics: Administration, Intravenous; Antithrombins; Electrocardiography; Hemorrhage; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk Assessment; Stents; Thrombosis

To evaluate the safety, effectiveness, and dosing of off-label bivalirudin to argatroban and lepirudin in patients with heparin-induced thrombocytopenia (HIT) using a new pharmacist driven protocol.. Retrospective cohort study of forty eight patients treated with lepirudin, argatroban, or bivalirudin from November 2010 to February 2012 for suspected HIT. Patients were excluded if the bivalirudin therapy was being used for acute coronary syndrome or if the treatment duration was less than 24 hours. The primary endpoint was time to therapeutic activated partial thromboplastin time (aPTT 50-90 seconds for argatroban and bivalirudin and 50-85 seconds for lepirudin). The secondary endpoints were elevation in international normalized ratio (INR), bleeding episodes, and percent time in aPTT target range.. Patients receiving bivalirudin reached a therapeutic aPTT more quickly than those receiving argatroban and lepirudin (3.7 hours vs. 14.2 hours vs. 14.7 hours, p <0.001). The INR was increased more in patients treated with argatroban than lepirudin and bivalirudin (1.3 vs. 0.3 vs. 0.4, p = 0.4). Clinically significant bleeding in patients treated with bivalirudin was significantly lower than that observed with argatroban or lepirudin (7% vs. 22% vs. 56%, p = 0.02). The average percentage of therapeutic aPTTs drawn was higher for patients treated with bivalirudin than those patients treated with argatroban and lepirudin (90% vs. 66% vs. 67%, p = 0.2).. A pharmacist-driven protocol for bivalirudin provided a significantly shorter time to therapeutic aPTT and lower bleeding rate for patients being treated for HIT when compared to lepirudin and argatroban. A larger study should be considered to confirm the results of this single center study.

Topics: Aged; Anticoagulants; Antithrombins; Arginine; Dose-Response Relationship, Drug; Female; Hemorrhage; Heparin; Hirudins; Humans; International Normalized Ratio; Male; Middle Aged; Partial Thromboplastin Time; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Retrospective Studies; Sulfonamides; Thrombocytopenia

To determine the impact of suture-mediated vascular closure devices (VCDs) on net adverse clinical events (NACEs) after balloon aortic valvuloplasty (BAV).. Ischemic and bleeding complications are common following transfemoral BAV; however, previous studies have been single center and limited by varying definitions of major bleeding.. The Effect of Bivalirudin on Aortic Valve Intervention Outcomes (BRAVOs) study was a retrospective observational study conducted at two high-volume academic centers over a 6-year period designed to compare the effect of bivalirudin versus unfractionated heparin. This is a subanalysis of 428 consecutive patients who underwent BAV (with 10-13 French sheaths) to compare the effect of hemostasis with VCDs versus manual compression utilizing standardized definitions. NACE was defined as the composite of major bleeding and major adverse clinical events (MACEs). All events were adjudicated by an independent clinical events committee who were blinded to antithrombin use.. Preclosure was performed in 269 (62.8%) of patients. While bivalirudin was used more frequently in those with pre-closure (60.6% vs. 37.7%, P < 0.001), a history of prior BAV (11.1% vs. 3.6%, P = 0.04) and peripheral vascular disease (30.7% vs. 19.7%, P = 0.01) was more common in those not undergoing preclosure (n = 159, 37%). Other clinical and demographic features were well balanced between groups. Vascular closure was associated with a significant reduction in NACE (24.5% vs. 10.0% P < 0.001). Results remained significant after adjusting for baseline differences and bivalirudin use (OR 0.38, 95% CI: 0.21-0.68; P = 0.001).. Our study suggests that suture-mediated vascular closure is associated with a substantial reduction in NACE after transfemoral BAV. Large randomized clinical trials should be conducted to confirm our results.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Balloon Valvuloplasty; Chi-Square Distribution; Equipment Design; Female; Femoral Artery; Florida; Hemorrhage; Hemostatic Techniques; Heparin; Hirudins; Hospitals, High-Volume; Humans; Logistic Models; Male; Multivariate Analysis; New York City; Odds Ratio; Peptide Fragments; Punctures; Recombinant Proteins; Retrospective Studies; Risk Factors; Suture Techniques; Treatment Outcome

We aimed to assess the impact of bleeding after percutaneous coronary intervention (PCI) on the outcome of patients >75 years of age.. Limited information exists on the impact of post-PCI bleeding on the outcome in elderly patients.. This study included 3,255 patients >75 years of age. Bleeding events were assessed using the Bleeding Academic Research Consortium (BARC) criteria. The primary outcome was 1-year mortality.. Within 30 days after PCI, bleeding occurred in 501 patients (15.4%). Bleeding according to BARC was: class 1 (170 patients; 33.9%), class 2 (81 patients; 16.2%), class 3a (177 patients; 35.3%), class 3b (65 patients; 13.0%), class 3c (four patients; 0.8%), and class 4 (four patients; 0.8%). There were 201 deaths within the first year after PCI: 61 deaths (12.3%) among bleeders and 140 deaths (5.1%) among nonbleeders (adjusted hazard ratio = 2.03, 95% confidence interval [CI] 1.42-2.91, P < 0.001). Bleeding improved the discriminatory power of multivariable model for mortality prediction (P = 0.001). Female sex (adjusted odds ratio [OR] = 1.49 [1.17-1.88], P = 0.001) and reduced renal function (adjusted OR = 1.30 [1.04-1.63], P = 0.019 for each 30 ml/min decrease in the creatinine clearance) were independent associates of increased bleeding risk. Bivalirudin reduced the bleeding risk by 24% compared with unfractionated heparin and 33% compared with abciximab plus unfractionated heparin.. Post-PCI bleeding is an important prognostic factor in patients >75 years of age. The risk for bleeding in this age category is increased in women and patients with impaired renal function. Bleeding risk is reduced by bivalirudin.

Topics: Age Factors; Aged; Aged, 80 and over; Antithrombins; Chi-Square Distribution; Female; Hemorrhage; Hirudins; Humans; Incidence; Kaplan-Meier Estimate; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Percutaneous coronary intervention (PCI)-related risks are increased among patients with left main disease (LMD). The aim was to evaluate the impact of antithrombotic therapy on outcomes after LMD PCI in a predominantly ACS population.. One hundred and seventy-seven patients undergoing LMD PCI were identified in a pooled dataset of 14,326 patients from three large randomised trials comparing treatment with heparin plus glycoprotein IIb/IIIa inhibitors (GPI) or bivalirudin alone, including the REPLACE-2, ACUITY and HORIZONS-AMI trials. Overall, net adverse clinical events (NACE) and non-CABG major bleedings at 30 days occurred more frequently in patients undergoing LMD PCI compared to the overall non-LMD PCI population (NACE: 19.8% vs. 10.6%, p≤0.001, major bleeding: 9.6% vs. 4.6%, p≤0.001). In the LMD group, bivalirudin was associated with significantly less non-CABG related major bleeding compared to heparin+GPI (4.5% versus 14.6%, relative risk [RR] 0.27, 95% CI: 0.09-0.83; p=0.013), while the composite ischaemic endpoint (death/MI/TVR) at 30 days was similar in the two groups (11.4% vs. 12.4%, p=0.513) resulting in a benefit on NACE for bivalirudin over heparin+GPI (14.8% vs. 24.7%; RR 0.53; p=0.039).. Among patients undergoing LMD PCI, the use of bivalirudin instead of heparin+GPI resulted in significantly less major bleeding and improved short-term net clinical outcome. Bivalirudin may be the preferred anticoagulation strategy in LMD PCI patients.

Topics: Abciximab; Aged; Aged, 80 and over; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Coronary Artery Disease; Eptifibatide; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Peptide Fragments; Peptides; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Several percutaneous coronary intervention (PCI) trials have established that the use of bivalirudin (BIV) is associated with improved patient outcomes and substantial hospital cost savings, relative to heparin (HEP)-based regimens±glycoprotein IIb/IIIa inhibitors (GPIs). Whether these benefits persist with the use of prasugrel, a new third-generation oral thienopyridine, has not been previously evaluated.. Using the Premier hospital database, 6986 patients treated with prasugrel who underwent elective, urgent, or primary PCI between quarter 3, 2009 and quarter 4, 2010 from 166 US hospitals were identified. These patients received either BIV (n=3377) or HEP±GPI (n=3609) as procedural anticoagulation. Outcomes of interest included bleeding, transfusions, death, and hospital length of stay (LOS). To control for patient and hospital-level characteristics, propensity score-matching (PSM) analyses were performed.. Mortality, clinically apparent bleeding, clinically apparent bleeding requiring transfusion, any transfusions, and LOS were all lower in patients treated with BIV as compared with patients treated with HEP±GPI. After PSM, the rate of transfusion was significantly lower with BIV (odds ratio: 0.57, 95% confidence interval: 0.34-0.96), and the hospital LOS was significantly shorter in patients treated with BIV compared with those treated with HEP±GPI (0.9±2.0 vs 1.2±2.3 days, P<0.0001).. In patients undergoing PCI and treated with prasugrel, the use of BIV rather than HEP±GPI is associated with significantly lower transfusion rate and LOS. These results suggest that the previously documented safety and cost-effectiveness benefits of BIV remain applicable when prasugrel is used.

Topics: Aged; Anticoagulants; Blood Transfusion; Chi-Square Distribution; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Length of Stay; Male; Middle Aged; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Recombinant Proteins; Retrospective Studies; Risk Factors; Thiophenes; Time Factors; Treatment Outcome; United States

We sought to assess if bivalirudin use during balloon aortic valvuloplasty (BAV) would affect clinical outcomes compared with heparin.. We compared the outcomes of consecutive patients who underwent elective or urgent BAV with intraprocedural use of bivalirudin or heparin at two high-volume centres. All in-hospital events post BAV were adjudicated by an independent, blinded clinical events committee. Of 427 patients, 223 patients (52.2%) received bivalirudin and 204 (47.8%) received heparin. Compared with patients who received heparin, patients who received bivalirudin had significantly less major bleeding (4.9% vs. 13.2%, p=0.003). Net adverse clinical events (NACE, major bleeding or major adverse cardiovascular events [MACE]) were also reduced (11.2% vs. 20.1%, p=0.01). There was no significant difference in the rates of MACE (mortality, myocardial infarction or stroke, 6.7% vs. 11.3%, p=0.1), or vascular complications (major, 2.7% vs. 2.0%; minor, 4.5% vs. 4.9%; p=0.83). After multivariate analysis controlling for vascular preclosure, the use of bivalirudin remained independently associated with reduced major bleeding (OR 0.37; 95% CI: 0.16 to 0.84; p=0.02) while the association was attenuated in propensity-adjusted analysis (OR 0.44, 95% CI: 0.18 to 1.07, p=0.08).. In this registry of patients with severe aortic stenosis, bivalirudin as compared to heparin resulted in improved in-hospital outcomes post BAV in terms of reduced major bleeding, similar MACE and reduced NACE. If verified in a randomised study and extended to the transcatheter aortic valve implantation (TAVI) population, these results might indicate a potential benefit for patients undergoing such procedures.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve Stenosis; Balloon Valvuloplasty; Female; Florida; Hemorrhage; Heparin; Hirudins; Hospitals, High-Volume; Humans; Logistic Models; Male; Multivariate Analysis; Myocardial Infarction; New York City; Odds Ratio; Peptide Fragments; Propensity Score; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome

Little is known about the use of bivalirudin in "real life". In the context of contemporary antiplatelet treatment, we aimed to assess bivalirudin treatment patterns and short-term (one-month) outcome.. Greek Antiplatelet Registry (GRAPE) is a prospective, observational, multicenter cohort study of consecutive, moderate-to-high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI). We assessed bivalirudin treatment patterns and predictive factors for its use. Combined in-hospital and one-month major adverse cardiovascular events (MACE, including death, myocardial infarction, urgent revascularization, and stroke), and bleeding events according to Bleeding Academic Research Consortium (BARC) criteria were analyzed after propensity matching.. Of 2047 registered patients, 480 (23.4%) were treated with bivalirudin. Multivariate analysis (C statistic 0.77, 0.75-0.80 95% CIs, P < 0.001) revealed as factors favoring bivalirudin use primary PCI, radial arterial access, presentation with positive biomarkers and use of novel P2Y12 inhibitor, whereas IIb/IIIa inhibitor administration did not. Regional trends also affected bivalirudin's choice. In 370 propensity-matched pairs of patients who received or not bivalirudin, MACE, BARC type 1, 2 and 3 did not differ between groups: 4.1%, 21.9%, 3.2%, 3.5% and 5.1%, 18.9%, 2.7%, 4.3%, respectively, P = nonsignificant for all.. In a "real life", contemporary antiplatelet treatment registry, clinical, laboratory and logistic factors affect bivalirudin's choice, while there are no differences in one-month outcome between bivalirudin-treated and non-bivalirudin-treated patients.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Female; Greece; Hemorrhage; Hirudins; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Patient Selection; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Prospective Studies; Recombinant Proteins; Recurrence; Registries; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome

Bleeding complications after percutaneous coronary intervention (PCI) have been associated with higher short and long-term mortality. Bivalirudin has been shown to reduce bleeding complications in patients who underwent PCI; however, the impact of anemia on bleeding complications and long-term mortality has not been studied. A total of 11,991 patients who underwent PCI over a period of 8 years with bivalirudin as the primary antithrombotic agent were included. Anemia was defined according to the World Health Organization definition. Bleeding complications were prospectively collected. Survival analysis was performed using multivariable Cox proportional hazards models. Of the 11,991 patients, 4,815 patients (40%) had baseline anemia. Major bleeding occurred in 3.3% of patients with anemia compared with 0.7% of patients without anemia (p <0.001) driven largely by transfusion events. In the overall study population, major bleeding was a significant predictor of mortality (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.04 to 1.8, p = 0.027) at a mean follow-up of 2.6 years (interquartile range 1.4 to 3.5). In patients with anemia, major bleeding remained an independent predictor of mortality (HR 1.5, 95% CI 1.1 to 2.0, p = 0.008); however, in patients without anemia, it did not (HR 1.25, 95% CI 0.52 to 3.03, p = 0.62). In patients who underwent PCI with bivalirudin therapy, major bleeding is associated with early and long-term mortality, which is more pronounced in patients with baseline anemia.

Topics: Aged; Anemia, Hypochromic; Antithrombins; Female; Hemorrhage; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Recombinant Proteins

The prospective EUROVISION Registry was designed to capture patterns of use and short term outcomes in consecutive patients undergoing PCI with bivalirudin (BIV) in European centres.. A total of 2018 consecutive BIV-treated patients were included from 58 sites in 5 countries (Germany, Italy, France, Austria, United Kingdom). In-hospital and 30-day outcomes were prospectively collected and included: death, myocardial infarction (MI), stroke, urgent revascularization (URV), major and minor bleeding, stent thrombosis (ST) and thrombocytopenia (TCP).. In this all-comer population, indication for PCI included STEMI (34%), NSTEMI (25%), unstable angina (16%) and stable angina (26%). Diabetes was present in 24% of patients and 30% of cases were performed via radial access. Preloading with a P2Y12 inhibitor was frequent (74%) while procedural glycoprotein inhibitor (GPI) use was low at 4.2%. Almost half (45%) of patients had received at least one additional anticoagulant prior to receiving BIV for PCI. The overall 30-day mortality was 1.0%, with low rates of MI (1.1%), URV (0.8%), ST (0.3%) and stroke (0.2%). The rate of ACUITY major bleeding was 1.6% and no TCP was reported. Dosing variations representing possible under- or over-dosing of BIV were frequent at 35%.. In this prospective registry of consecutive patients intended for PCI, use of BIV was associated with low rates of ischemic complications and excellent safety.

Topics: Aged; Angina, Stable; Angina, Unstable; Anticoagulants; Antithrombins; Coronary Thrombosis; Europe; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Registries; Risk Factors; Stents; Stroke

The aim of this study was to assess the impact of bleeding after percutaneous coronary intervention (PCI) on the outcome of patients with type 2 diabetes.. This study included 4,329 diabetic patients who underwent PCI. Bleeding was assessed using the Bleeding Academic Research Consortium criteria. The primary outcome was one-year mortality. Bleeding events occurred in 474 patients (10.9%). Access-site and non-access-site bleeds occurred in 274 patients (58%) and 200 patients (42%), respectively. Within the first year after PCI there were 198 deaths: 45 deaths (9.6%) among patients with bleeding and 153 deaths (4.0%) among patients without bleeding (adjusted hazard ratio=2.04 [95% confidence interval 1.38-3.00], p<0.001). There were 25 deaths (12.7%) among patients with non-access-site bleeding and 20 deaths (7.4%) among patients with access-site bleeding (odds ratio [OR]=3.45 [2.20-5.41], p<0.001 for non-access-site bleeding vs. no bleeding and OR=1.90 [1.17-3.01], p=0.008 for access-site bleeding vs. no bleeding). Bleeding improved the discriminatory power of the multivariable model for mortality prediction (p=0.002).. In patients with diabetes undergoing PCI, occurrence of bleeding within the first 30 days after PCI was associated with a significant increase in the risk of one-year mortality.

Topics: Abciximab; Aged; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Aspirin; Clopidogrel; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Logistic Models; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prognosis; Proportional Hazards Models; Recombinant Proteins; Risk Factors; Stents; Ticlopidine

Optimal treatment of acute ST-elevation myocardial infarction (STEMI) involves rapid diagnosis, and transfer to a cardiac centre capable of percutaneous coronary intervention (PCI) for immediate mechanical revascularisation. Successful treatment requires rapid return of perfusion to the myocardium achieved by thromboaspiration, passivation of the culprit lesion with stent scaffolding and systemic inhibition of thrombosis and platelet activation. A delicate balance exists between thrombosis and bleeding and consequently anti-thrombotic and antiplatelet treatment regimens continue to evolve. The desire to achieve reperfusion as soon as possible, in the setting of high platelet reactivity, requires potent and fast-acting anti-thrombotic/anti-platelet therapies. The associated bleeding risk may be minimised by use of short-acting anti-thrombotic intravenous agents. However, effective oral platelet inhibition is required to prevent recurrent thrombosis. The interaction between baseline platelet reactivity, timing of revascularisation and effective inhibition of thrombosis is yet to be formally investigated.. We present a protocol for a prospective observational study in patients presenting with acute STEMI treated with primary PCI (PPCI) and receiving bolus/infusion bivalirudin and prasugrel therapy. The objective of this study is to describe variation in platelet reactivity, as measured by the multiplate platelet function analyser, at presentation, the end of the PPCI procedure and 1, 2, & 24 hours post-procedure. We intend to assess the prevalence of high residual platelet reactivity within 24 hours of PPCI in acute STEMI patients receiving prasugrel and bivalirudin. Additionally, we will investigate the association between high platelet reactivity before and after PPCI and the door-to-procedure completion time.This is a single centre study with a target sample size of 108 participants.. The baseline platelet reactivity on presentation with a STEMI may impact on the effect of acute anti-thrombotic and anti-platelet therapy and expose patients to a heightened risk of bleeding or ongoing thrombosis. This study will define the baseline variation in platelet reactivity in a population of patients experiencing acute STEMI and assess the pharmacodynamic response to combined treatment with bivalirudin and prasugrel. The data obtained from this trial will be hypothesis generating for future trials testing alternative pharmacotherapies in the acute phase of treatment for STEMI.. This study has approval from Wiltshire research ethics committee (10/H0106/87) and is registered with current controlled trials (http://www.controlled-trials.com/ISRCTN82257414).

Topics: Blood Platelets; Clinical Protocols; Coronary Thrombosis; Drug Monitoring; Drug Therapy, Combination; England; Hemorrhage; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Point-of-Care Systems; Prasugrel Hydrochloride; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Research Design; Thiophenes; Time Factors; Treatment Outcome

The use of bivalirudin versus unfractionated heparin monotherapy in patients without ST-segment-elevation myocardial infarction is not well defined.. The study population consisted of patients enrolled in the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease, who underwent percutaneous coronary intervention with either unfractionated heparin or bivalirudin monotherapy. Propensity score matching was used to adjust for baseline characteristics. The primary bleeding (in-hospital composite bleeding-access site bleeding, thrombolysis in myocardial infarction major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/myocardial infarction/unplanned repeat revascularization at 12 months) were evaluated. Propensity score matching yielded 1036 patients with non-ST-segment-elevation acute coronary syndromes and 2062 patients with stable ischemic heart disease. For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01; number need to treat=30) without increase in either primary (difference, 1.2% [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable ischemic heart disease cohort, bivalirudin use was associated with lower bleeding (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7% to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy.. Among patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease undergoing percutaneous coronary intervention, bivalirudin use during percutaneous coronary intervention when compared with unfractionated heparin monotherapy was associated with lower bleeding without significant increase in ischemic outcomes or stent thrombosis.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Cohort Studies; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Registries; Risk Factors; Thrombosis; Treatment Outcome

Reducing bleeding events is a priority in patients diagnosed with acute coronary syndromes (ACS). The effectiveness of optimization measures for reducing abciximab-related bleeding was evaluated through the implementation of a pilot program developed by the Pharmacy and the Cardiology Departments at a tertiary-care hospital.. Percentage of bleeding events.. Intervention was effective in reducing the incidence of the three factors associated with an increased risk of bleeding between the pre-intervention phase (n = 86) and the post-intervention phase (n = 73): unknown body weight (24.4 vs. 1.4 %, p = 0.0001), overdosing (31.4 vs. 0 %, p < 0.0001) and combination with bivalirudin (12.8 vs. 1.4 %, p = 0.016). Bleeding events associated with these factors were numerically reduced in all three cases but these differences were not statistically significant between both periods.. The implementation of a multidisciplinary prevention program can reduce situations associated with an increased risk of bleeding in patients treated with abciximab. Larger scale trials are needed to confirm whether such programs can also reduce the incidence of bleeding at a statistically significant level.

Topics: Abciximab; Acute Coronary Syndrome; Aged; Antibodies, Monoclonal; Antithrombins; Body Weight; Cohort Studies; Drug Dosage Calculations; Drug Therapy, Combination; Female; Hemorrhage; Hirudins; Humans; Immunoglobulin Fab Fragments; Incidence; Male; Middle Aged; Peptide Fragments; Pharmacy Service, Hospital; Pilot Projects; Platelet Aggregation Inhibitors; Recombinant Proteins; Retrospective Studies; Risk Factors; Spain; Tertiary Care Centers; Workforce

Parenteral direct thrombin inhibitors (DTIs) may be used in pediatric patients with contraindications to heparin therapy, such as heparin-induced thrombocytopenia. Few data exist regarding the use of DTIs in pediatric patients.. To characterize the use of DTIs in pediatric patients, including monitoring strategies and bleeding complications.. A retrospective descriptive study was designed and the Pediatric Health Information System database was queried from 2004 to 2011 for pediatric patients receiving a parenteral DTI. Patient demographic and hospital data, mortality, disease state, and procedure information (from International Classification of Diseases, Ninth Revision codes) were collected from the query. DTI monitoring information was also collected. Patients were divided into 2 time periods (2004-2007, 2008-2011) to evaluate trends.. Two hundred eight patients met study criteria (50.9% male, 64.4% white), and children (2-12 years of age) represented 34.6% of the population. Congenital heart disease was present in 43.8% and cardiovascular surgical procedure occurred in 28.4%. Argatroban was most commonly used (73.1%) and bivalirudin use increased (P < .001). Bleeding complications were present in 37.9% of patients and mortality was 19.7%. Bleeding complications were associated with lepirudin (62.5%) and argatroban (41.7%) more often as compared with bivalirudin (18.8%) (P < .001). Activated partial thromboplastin time and prothrombin time were used more often in patients receiving argatroban and lepirudin in comparison with bivalirudin, and thrombin time was used more often in patients receiving lepirudin (P < .001). Activated clotting time use increased over time (5.1% versus 17.5%, P = .02).. Pediatric use of DTIs is infrequent and occurs in patients with high morbidity and mortality.

Topics: Adolescent; Age Factors; Antithrombins; Arginine; Child; Child, Preschool; Databases, Factual; Female; Health Information Systems; Hemorrhage; Hirudins; Humans; Incidence; Infant; Infant, Newborn; Infusions, Parenteral; Male; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Retrospective Studies; Sulfonamides; Thrombocytopenia; Young Adult

Unfractionated heparin (UFH) is the anticoagulant of choice for extracorporeal membrane oxygenation (ECMO), but bivalirudin can be used as an alternative. The purpose of the present study is to investigate the existence of a heparin-like effect (HLE) during heparin-free ECMO.. This is a retrospective study on patients treated with ECMO and receiving bivalirudin as the sole anticoagulant. Thromboelastography (TEG) tests with and without heparinase were recorded during the ECMO duration. A total of 41 patients (22 pediatrics and 19 adults) treated with ECMO after cardiac surgery procedures and receiving only bivalirudin-based anticoagulation were studied. Based on the presence of a different reaction time (R-time) between the TEG test with heparinase or without heparinase we defined the presence of a HLE. Survival to hospital discharge, liver failure, sepsis, bleeding and transfusion rate were analyzed for association with HLE with univariate tests.. HLE was detected in 56.1% of the patients. R-times were significantly shorter in tests done with heparinase versus without heparinase during the first seven days on ECMO. Patients with HLE had a significantly (P = 0.046) higher rate of sepsis (30%) than patients without HLE (5.6%) at a Pearson's chi-square test.. A heparin-like effect is common during ECMO, and most likely due to a release of heparinoids from the glycocalyx and the mast cells, as a consequence of sepsis or of the systemic inflammatory reaction triggered by the contact of blood with foreign surfaces.

Topics: Adult; Anticoagulants; Cardiac Surgical Procedures; Child; Child, Preschool; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Hirudins; Humans; Infant; Infant, Newborn; Male; Partial Thromboplastin Time; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Thrombelastography; Time Factors

Within a clinical trial population, direct thrombin inhibition using bivalirudin in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with a reduction in mortality and major bleeding compared to heparin/glycoprotein IIb/IIIa receptor inhibition (GPI), but a higher incidence of acute stent thrombosis (ST), particularly in the absence of pre-procedural heparin. The safety and efficacy of bivalirudin in an all-comer, real-world primary PCI setting is unknown.. 968 consecutive STEMI patients (mean age 63 years, 72% male, 42% anterior STEMI, 3.7% cardiogenic shock) undergoing primary PCI with bivalirudin as the recommended anticoagulation, and with heparin/GPI (abciximab) as an alternative, were prospectively followed. Bivalirudin was administered as a bolus, high-dose procedural infusion and, unlike the HORIZONS-AMI trial, as a low-dose infusion for four hours post-PCI. Additional heparin was not routinely given. Mortality, major adverse cardiovascular events (MACE), major bleeding and ST were assessed at 30 days. Initial antithrombotic therapy was bivalirudin in 885 patients (91%), of whom 123 (13.9%) received additional antithrombin therapy, and 114 (11.8%) "bail-out" GPI. Outcomes for bivalirudin-treated patients were; mortality 5.2%, MACE 7.5%, major bleeding 3.8%. The incidence of acute ST was 1.0%, including in the absence of additional heparin (1.2%). Most cases of acute ST (7/9) occurred in the first four hours post-PCI. There was no significant difference in outcomes between patients treated with bivalirudin versus heparin/GPI.. Routine use of bivalirudin in a real-world primary PCI population was associated with good 30-day outcomes. Acute stent thrombosis was infrequent, even without additional heparin. A continued low-dose infusion of bivalirudin did not appear to offer protection against very early stent thrombosis.

Topics: Aged; Antithrombins; Coronary Thrombosis; Drug Administration Schedule; Female; Hemorrhage; Hirudins; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

Topics: Antithrombins; Female; Groin; Hemorrhage; Hemostatic Techniques; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

This study sought to assess whether incorporation of routine bleeding risk estimates affected the utilization of bivalirudin during percutaneous coronary intervention (PCI).. Bivalirudin use during PCI has been shown to reduce bleeding complications. However, a risk-treatment paradox exists, in which patients at highest risk for bleeding are least likely to receive bivalirudin. Whether routine estimation of individualized bleeding risk can affect physicians' use of bivalirudin is unknown.. PCI data from a single health system between 2007 and 2011 were analyzed. Beginning in July 2009, individualized bleeding risk estimates were provided immediately preceding PCI. Using a pre-post design, we compared bivalirudin use before and after this implementation, for patients across 3 strata of bleeding risk (<1%, 1% to 3%, and >3%).. Data from 6,491 PCI procedures were analyzed. Overall, bivalirudin use increased in the post-implementation period (26.9% vs. 34.2%, p < 0.001). Bivalirudin use increased in intermediate (27% to 35%, p < 0.001) and high bleeding risk patients (25% to 43%, p < 0.001), and decreased in low-risk patients (30% to 25%, p = 0.014). During the same period, bleeding complications decreased in intermediate-risk (3.4% to 1.8%, p = 0.009) and high-risk (6.9% to 3.7%, p = 0.005) patients and remained unchanged in low-risk patients (1.1% to 1.0%, p = 0.976).. There was an increase in bivalirudin use and a lower incidence of bleeding after the incorporation of individualized bleeding risk estimates into clinical practice. This implementation led to a reversal of the risk-treatment paradox, through a rational increase in bivalirudin use in patients at intermediate and high bleeding risk and decreased use in lower-risk patients.

Topics: Aged; Antithrombins; Clinical Competence; Coronary Disease; Female; Hemorrhage; Hirudins; Humans; Incidence; Male; Middle Aged; Missouri; Peptide Fragments; Percutaneous Coronary Intervention; Preoperative Period; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors

The direct thrombin inhibitor, bivalirudin, is associated with similar efficacy and superior safety in patients undergoing percutaneous coronary intervention. However, the role of direct thrombin inhibitors in carotid artery stenting is not well defined. The objective of this study was to compare the safety and effectiveness of bivalirudin and unfractionated heparin (UFH) for carotid artery stenting. We hypothesized that bivalirudin would be associated with less in-hospital postprocedure bleeding than UFH but similar rates of in-hospital and 30-day ischemic outcomes.. We compared the incidence of in-hospital hemorrhagic and in-hospital/30-day ischemic outcomes among patients in the CARE Registry who underwent carotid artery stenting between May 2005 and March 2012 using bivalirudin or UFH. Propensity score matching was used to obtain a balanced cohort of 3555 patients in each treatment group. Patients treated with bivalirudin had a significantly lower incidence of bleeding or hematoma requiring red blood cell transfusions (0.9% versus 1.5%; odds ratio, 0.57 [0.36-0.89]; P=0.01) when compared with UFH-treated patients. The incidence of in-hospital and 30-day ischemic outcomes, including death, myocardial infarction, stroke, transient ischemic attack, and the composite outcome, death/myocardial infarction/stroke, did not differ significantly between groups.. Bivalirudin was associated with lower rates of hemorrhagic outcomes compared with UFH during the index hospitalization for carotid artery stenting. In-hospital and 30-day ischemic events were similar between the 2 groups. Randomized comparisons of these agents are needed to confirm these findings.

Topics: Aged; Aged, 80 and over; Angioplasty; Anticoagulants; Antithrombins; Brain Ischemia; Carotid Stenosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Male; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Registries; Risk Factors; Stents; Stroke

Topics: Angioplasty; Brain Ischemia; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Stents

Bivalirudin has emerged as a suitable alternative anticoagulant to unfractionated heparin and low-molecular-weight heparins during percutaneous coronary intervention (PCI) procedures in the management of coronary artery disease and acute coronary syndromes (ACS). In clinical trials, bivalirudin dosing was standardized, and activated clotting time (ACT) did not influence dosing adjustments. The role of ACT monitoring of bivalirudin in PCI is not defined based on current practice guidelines.. The hypothesis of this study is that hyper- and hypo-ACT responses to bivalirudin in PCI may be associated with excessive bleeding or thrombotic complications.. The planned protocol screened all patients who received bivalirudin therapy and ACT monitoring during PCI in a single center's cardiac catheterization laboratory from July 2009 to June 2010. The first ACT monitored 5 to 60 minutes after bivalirudin initiation was screened for inclusion. Values above 800 seconds and below 300 seconds were included as hyper- and hypo-ACT responses, respectively. Outcomes assessed include thrombotic and bleeding complications.. There were 32 patients identified as hyper-responders and 20 patients identified as hypo-responders. There were no significant thrombotic or bleeding complications in the hyper-responder group. There was 1 case (1/20, 5%) of angiographically confirmed acute stent thrombosis immediately following the placement of 5 adjoining bare-metal stents in the right coronary artery of a hypo-responder.. Hyper-ACT responses to bivalirudin therapy in PCI were not associated with additional bleeding risk. Bivalirudin may not adequately protect hypo-ACT responders against thrombotic complications during PCI.

Topics: Acute Coronary Syndrome; Antithrombins; Blood Coagulation; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Retrospective Studies; Risk Factors; Thrombosis; Time Factors; Whole Blood Coagulation Time

A simplified dosing nomogram to assist nurses in adjusting the rate of i.v. bivalirudin administration in cases of heparin-induced thrombocytopenia (HIT) is described.. To facilitate the availability of bivalirudin [corrected] as an alternative direct thrombin inhibitor (DTI) for patients with HIT at The Ohio State University Wexner Medical Center (OSUWMC), a team of clinical pharmacists developed a nomogram designed to simplify infusion dosage adjustments by nurses. In contrast to bivalirudin nomograms requiring patient-specific, percentage-based dose adjustments, the nomogram developed at OSUWMC specifies fixed adjustments (0.005 or 0.01 mg/kg/hr) according to the current activated partial thromboplastin time (aPTT) value relative to aPTT goals. During pilot testing over three years, the nomogram was used to guide dosage adjustments in 65 adult patients receiving continuous infusions of bivalirudin for suspected or confirmed HIT in intensive care units. Overall, the use of the nomogram resulted in adequate anticoagulation, with 53.7% of all measured aPTT values in the target range; 30.5% of aPTT values were below target, and 15.8% of values were above target. The median time to steady state was 11.0 hours (range, 5.0-31.8 hours), and bleeding rates were consistent with those reported in the literature. Nurse adherence to the nomogram was 100%, and no dosing errors occurred during a total of 487 dosage changes. Based on the pilot study results, the nomogram was refined to improve initial dosing for patients with creatinine clearance values of >30 mL/min; other refinements were made to enhance the safety of bivalirudin therapy for HIT in patients with severe renal impairment.. A nurse-driven, sliding-scale nomogram for bivalirudin therapy in patients with HIT provided a simple dosing protocol and resulted in a high rate of adherence by nurses.

Topics: Aged; Disease Management; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Nomograms; Nurse's Role; Peptide Fragments; Pilot Projects; Program Development; Recombinant Proteins; Thrombocytopenia

We investigated the feasibility and safety of intra-arterial bivalirudin bolus during primary angioplasty.. Bivalirudin has been shown to be an effective and safe anticoagulant during angioplasty. However, in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial, the bivalirudin group experienced higher acute stent thrombosis rate compared with the heparin and glycoprotein IIb/IIIa inhibitor group. One possible explanation is suboptimal systemic administration.. To prevent this possibility and to potentially prevent acute stent thrombosis, we administered intra-arterial bivalirudin bolus during primary angioplasty in 100 consecutive patients.. Our observational study suggests safety with no bleeding episode and no observed acute stent thrombosis.. We conclude that intra-arterial bivalirudin bolus during primary angioplasty is safe and could ensure effective systemic delivery of bivalirudin.

Topics: Aged; Antithrombins; Coronary Thrombosis; Feasibility Studies; Female; Hemorrhage; Hirudins; Humans; Infusions, Intravenous; Injections, Intra-Arterial; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Stents; Treatment Outcome

Bleeding is a common, noncardiac, preventable complication of percutaneous coronary intervention. We compared the relative safety of radial access and bivalirudin in percutaneous coronary intervention.. From CathPCI Registry, we determined the association between the site of arterial access, bivalirudin, and periprocedural bleeding rates in 501 017 patients. Radial access patients receiving heparin (radial group) were compared with those receiving bivalirudin (radial combination group). Femoral access patients who had bivalirudin and a vascular closure device served as a reference group (femoral group). An inverse probability weighting analysis incorporating propensity scores was used to compare groups. The overall rate of bleeding was 2.59%. It was 2.71% in the femoral group, 2.5% in the radial group, and 1.82% in the radial combination groups (P<0.001). When compared with femoral group, the adjusted odds ratio for bleeding was significantly lower for patients with radial combination group (odds ratio, 0.79; 95% confidence interval, 0.72-0.86), but not for radial group (odds ratio, 0.96; 95% confidence interval, 0.88-1.05), unless patients treated with IIb/IIIa were excluded (radial group-IIb/IIIa odds ratio, 0.84; 95% confidence interval, 0.75-0.94).The number needed to treat to prevent 1 bleeding event with radial combination group was 138, whereas the number needed to treat to prevent 1 bleeding event in high-bleeding risk patients was 68.. In this observational analysis, the combination of bivalirudin and radial access was associated with reduced bleeding event rate. This benefit was present across the entire spectrum of preprocedural risk of bleeding, with or without exposure to IIb/IIIa inhibitors. These data support an adequately powered randomized trial comparing bleeding avoidance strategies.

Topics: Aged; Antithrombins; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Radial Artery; Recombinant Proteins; Registries; Risk

Use of bivalirudin has been associated with a reduction in the incidence of bleeding in patients undergoing percutaneous coronary intervention. Patients with chronic kidney disease, a known predictor of post-percutaneous coronary intervention bleeding, are under-represented in clinical trials.. We evaluated the outcome of 64,052 patients who underwent percutaneous coronary intervention from 2007 to 2009 at 33 hospitals in Michigan and were treated with bivalirudin (28,378) or with heparin and glycoprotein IIb/IIIa inhibitors (35,674). Propensity-matched analysis was adjusted for the nonrandomized use of the 2 strategies. Patients treated with bivalirudin were older, had a lower glomerular filtration rate, and had more comorbidities. Use of bivalirudin was associated with fewer transfusions (2.8% versus 4.2%; P<0.0001), gastrointestinal bleeds (0.5% versus 1.3%; P<0.0001), and vascular complications (1.0% versus 2.5%; P<0.0001), with no difference in survival. Bleeding complications were more common with worsening renal function, but use of bivalirudin was associated with less bleeding across the continuum of renal dysfunction.. The risk of bleeding after percutaneous coronary intervention increases with worsening chronic kidney disease. Bivalirudin was associated with a dramatically reduced risk of bleeding across all categories of renal dysfunction. Our study findings suggest that bivalirudin monotherapy is an acceptable, if not the more appropriate alternative, to heparin and glycoprotein IIb/IIIa inhibitors in patients with chronic kidney disease.

Topics: Aged; Antithrombins; Blue Cross Blue Shield Insurance Plans; Comorbidity; Coronary Artery Disease; Female; Hemorrhage; Hirudins; Humans; Incidence; Kidney; Male; Michigan; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Severity of Illness Index; Treatment Outcome

This study was undertaken to evaluate the safety of bivalirudin (BIV) use during percutaneous coronary intervention (PCI), following thrombolytic therapy in patients with ST-segment elevation myocardial infarction (STEMI).. BIV has emerged as a safer anticoagulant than unfractionated heparin (UFH) during primary PCI; however, its use in patients who receive thrombolytic therapy has not been established.. A consecutive series of 104 patients who presented with STEMI treated with full-dose thrombolytics and who subsequently received PCI within 6 hr was identified and analyzed. BIV use was compared with UFH for in-hospital bleeding and ischemic events. The primary end points were the rate of major bleeding and the rate of net adverse clinical events as defined in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial. The study cohort consisted of 104 patients, of whom 47 (45%) received BIV and 57 (55%) received UFH.. Patients on BIV were more frequently preloaded with clopidogrel, while intraprocedural glycoprotein IIb/IIIa inhibitors were used only in UFH patients. In-hospital death, ischemic events, and thrombolysis in myocardial infarction major bleeding occurred more frequently in patients treated with UFH. The net adverse clinical events rate was lower in the intraprocedural BIV group (3 [6.4%] vs. 12 [21.1%] UFH, P = 0.034).. The use of BIV in patients presenting with STEMI who were pretreated with thrombolytic therapy and who subsequently underwent PCI is safe and is associated with less ischemic and bleeding events when compared with UFH, and should be considered as the first line anticoagulant for these patients during PCI.

Topics: Adult; Aged; Anticoagulants; Antithrombins; Combined Modality Therapy; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Patient Selection; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Recurrence; Retrospective Studies; Risk Factors; Thrombolytic Therapy; Time Factors; Treatment Outcome

To investigate the safety and risk of vascular complications of arteriotomy closure devices (ACD) with the direct thrombin inhibitor bivalirudin in patients undergoing percutaneous coronary intervention (PCI).. ACDs and manual compression have been shown to have a similar risk of complications in the setting of PCI with heparin ± glycoprotein (GP) IIb/IIIa inhibitor usage. In many centers bivalirudin is becoming the most frequent type of anticoagulation used during PCI. We sought to determine the risk of vascular complications using Angio-Seal, Perclose, and manual compression for groin hemostasis using predominantly bivalirudin.. Our institution's interventional database retrospectively identified 14,354 consecutive patients undergoing PCI from 2000 to 2008. Patients were grouped by the adjunctive anticoagulation used (bivalirudin vs. heparin + GP IIb/IIIa inhibitors) as well as ACD employed. The incidence of complications was evaluated using multivariable analysis to account for baseline differences between groups.. Patients undergoing PCI with adjunctive bivalirudin had significantly fewer complications overall, regardless of closure method (2.9% vs. 8.7%, P < 0.001). The Perclose group had significantly fewer complications than the Angio-Seal and manual compression groups (3.9% vs. 5.6% vs. 9.0%, P < 0.001) respectively; the Angio-Seal group had significantly fewer complications than manual compression. Multivariable analysis also identified age ≥ 65, female gender, BMI ≤ 26, and operator as independent predictors of complications.. The use of adjunctive bivalirudin during PCI was associated with fewer vascular complications. In addition, the Perclose and Angio-Seal devices had significantly fewer complications than manual compression and women ≥ 65 are at highest risk.

Topics: Age Factors; Aged; Antithrombins; Body Mass Index; Chi-Square Distribution; Equipment Design; Female; Groin; Hemorrhage; Hemostatic Techniques; Heparin; Hirudins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Punctures; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Treatment Outcome

We sought to (1) determine the bleeding rates after primary percutaneous coronary intervention (PPCI) in our institution, where the default strategy has been transradial (TR) access in combination with unfractionated heparin (UFH) plus eptifibatide, and (2) compare these with the outcomes of patients treated with bivalirudin in HORIZONS-AMI.. HORIZONS-AMI demonstrated that in PPCI undertaken via the transfemoral route, routine use of bivalirudin was associated with lower bleeding rates and improved mortality compared to routine use of UFH plus glycoprotein IIb/IIIa inhibitor (GPI).. This was a single-center prospective registry of consecutive patients undergoing PPCI from January 2009 to August 2011 at the Queen Elizabeth Hospital Birmingham, UK. Thirty-day major bleeding was defined as per the HORIZONS-AMI criteria and also according to TIMI and GUSTO scales.. Of the 432 consecutive patients, 350 fulfilled entry criteria for HORIZONS-AMI. In contrast with HORIZONS-AMI, these subjects were older (62.5 ± 13.7 yr vs. 59.8 ± 11.1 yr, P < 0.05) with a higher rate of cardiogenic shock (6.3% vs. 0.8%, P < 0.0001). Despite this higher risk population, the rate of major bleeding was favorable (3.7% [95% CI: 2.0-6.3%] vs. 4.9% [4.0-6.1%], P = 0.32). Similarly, TIMI major bleeding (2.0% [0.8-4.1%] vs. 3.1% [2.3-3.4%], P = 0.10) and GUSTO severe or life-threatening bleeding (0.6% [0.1-2.5%] vs. 0.4% [0.2-0.9%], P = 0.75) were comparable.. Routine TR access for PPCI using UFH plus GPI is associated with a low 30-day rate of major bleeding equivalent to the bivalirudin arm of HORIZONS-AMI. Default transradial access for PPCI permits routine use of a GPI without the penalty of high bleeding rates.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Cardiac Catheterization; Coronary Thrombosis; England; Eptifibatide; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Prospective Studies; Radial Artery; Recombinant Proteins; Registries; Risk Factors; Shock, Cardiogenic; Time Factors; Treatment Outcome

Patients with acute myocardial infarction are at high risk of dying within the first hours after onset of coronary ischemia. Therefore, pharmacological intervention should be started in the prehospital setting. This study investigates the effect of the prehospital administration of bivalirudin on short-term morbidity and mortality compared to heparin plus abciximab in patients with ST-segment-elevation myocardial infarction (STEMI).. One hundred ninety-eight patients with STEMI treated with bivalirudin in the prehospital setting were prospectively collected. Coronary angiography was performed to identify the infarct-related artery. In case of a percutaneous coronary intervention, bivalirudin was given according to the guidelines. The historic control group consisted of 171 consecutive patients from the same myocardial infarction network treated with unfractioned heparin and abciximab administration before the admission to the emergency department of the percutaneous coronary intervention center. The primary outcome parameter was the incidence of major adverse cardiac events (recurrent myocardial infarction, stroke, death, target vessel revascularization for ischemia) within 30 days after the primary event.. The overall rate of major adverse cardiac events was significantly lower in the bivalirudin group compared to the abciximab group (7.6% vs 14.6%; P = .04). The number of major bleedings was significantly higher in the abciximab group compared to the bivalirudin group (11.8% vs 3.8%; P = .03).. The use of bivalirudin in the prehospital setting leads to a reduced rate of major cardiovascular events compared to a standard treatment with abciximab plus heparin. Bivalirudin is a reasonable choice of treatment in the prehospital setting for patients with STEMI.

Topics: Abciximab; Aged; Angioplasty; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Cardiac Catheterization; Drug Therapy, Combination; Emergency Medical Services; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Preoperative Care; Prospective Studies; Recombinant Proteins; Time Factors; Treatment Outcome

Limited data are available regarding adverse bleeding events associated with antithrombotic agents incorrectly dosed based on renal function in patients receiving percutaneous coronary intervention (PCI).. To compare the incidence of bleeding during their hospital stay in patients with reduced renal function receiving incorrect doses of bivalirudin or eptifibatide to the incidence of correct doses, based on manufacturer recommendations; secondary objectives were to determine the incidence of correct dosing based on manufacturer recommendations and the incidence of TIMI (Thrombolysis in Myocardial Infarction) major bleeding.. A chart review over a 32-month period showed that patients with reduced renal function who received either eptifibatide or bivalirudin during PCI were evaluated for correct dosing based on manufacturer recommendations, bleeding incidence according to the TIMI criteria, and extent of bleeding according to the TIMI and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) criteria.. One hundred ninety patients met inclusion criteria, 56 who received eptifibatide and 134 who received bivalirudin. Eptifibatide was dosed incorrectly in 64% of the patients. Patients receiving incorrectly dosed compared to correctly dosed eptifibatide experienced significantly more bleeding (64% vs 35%, respectively, p = 0.04), a greater extent of bleeding based on the TIMI and GUSTO criteria (p = 0.03 and p = 0.009, respectively), and had more TIMI major bleeding (19% vs 5%, respectively). Bivalirudin was dosed incorrectly in 28% of the patients. Patients receiving incorrectly dosed compared to correctly dosed bivalirudin experienced a significantly greater extent of bleeding based on the GUSTO criteria (p = 0.01). There was no significant difference between the incidence of bleeding (37% vs 21%, respectively; p = 0.06), extent of bleeding based on the TIMI criteria (p = 0.058), or incidence of TIMI major bleeding (5% vs 3%).. Patients receiving incorrectly dosed eptifibatide and bivalirudin are susceptible to adverse bleeding events. The occurrence of incorrect dosing offers an opportunity for pharmacist-driven institutional improvement.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Eptifibatide; Female; Glomerular Filtration Rate; Hemorrhage; Hirudins; Humans; Incidence; Male; Medical Records Systems, Computerized; Medication Errors; Middle Aged; Peptide Fragments; Peptides; Practice Guidelines as Topic; Recombinant Proteins; Renal Insufficiency; Thrombosis

Randomized trials show improved outcomes among acute coronary syndrome patients treated with bivalirudin. The objective of this analysis was to compare clinical and economic outcomes in ST-elevation myocardial infarction (STEMI) patients encountered in routine clinical practice undergoing primary percutaneous coronary intervention (PPCI), treated with bivalirudin or heparin+GP IIb/IIIa receptor inhibitor (heparin+GPI).. STEMI admissions from January 1, 2004 through March 31, 2008 among patients receiving PPCI and bivalirudin or heparin+GPI in the Premier hospital database were identified. The probability of receiving bivalirudin was estimated using individual and hospital variables; using propensity scores, each bivalirudin patient was matched to 3 heparin+GPI treated patients. The primary outcome was in-hospital death. Rates of bleeding, transfusion, length of stay, and in-hospital cost were secondary outcomes. There were 59,917 STEMI PPCIs receiving bivalirudin (n=6735) or heparin+GPI (n=53,182). Seventy-nine percent of bivalirudin patients matched, resulting in 21,316 STEMI PPCIs for analysis. Compared with heparin+GPI patients, bivalirudin patients had fewer deaths (3.2% versus 4.0%; P=0.011) and less inpatient bleeding (clinically apparent bleeding [6.9% versus 10.5%, P<0.0001], clinically apparent bleeding with transfusion [1.6% versus 3.0%, P<0.0001], and transfusion [5.9% versus 7.6%, P<0.0001]). Patients receiving bivalirudin had shorter average length of stay (mean 4.3 versus 4.5 days; P<0.0001), with lower in-hospital cost (mean $18,640 versus $19,967 [median $14,462 versus $16,003], P<0.0001).. This large "real-world" retrospective analysis demonstrates that bivalirudin therapy compared with heparin+GPI is associated with a lower rate of inpatient death, inpatient bleeding, and decreased overall in-hospital cost in STEMI patients undergoing PPCI.

Topics: Acute Coronary Syndrome; Adolescent; Adult; Aged; Aged, 80 and over; Angioplasty; Antithrombins; Coronary Vessels; Cost-Benefit Analysis; Electrocardiography; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult

Thrombin a key modulator of the complex process involved in coronary obstruction during acute ST-segment elevation myocardial is infarction. A correct and complete thrombin inhibition has to be achieved early in this setting and is complementary with fast and potent antiplatelet treatment. Bivalirudin, a direct thrombin inhibitor, has clearly shown to be an effective tool for acute coronary syndromes managed invasively, contemporarily causing fewer hemorragies. However, its efficacy has been questioned, mostly in cases of inadequate platelet inhibition and during primary PCI if compared with therapy with heparin and glycoprotein IIb/IIIa inhibitors due to an increase in acute stent thrombosis. Other modalities of infusion have been shown to improve the antithrombotic properties of bivalirudin, maintaining its safety profile. In this article, we discuss on the most recent studies on this drug in the catheterization laboratory during acute myocardial infarction.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Arrhythmias, Cardiac; Combined Modality Therapy; Hemorrhage; Hirudins; Humans; Infusions, Parenteral; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Postoperative Care; Recombinant Proteins; Risk; Thrombosis

Topics: Cardiac Catheterization; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Percutaneous coronary intervention (PCI) is the most commonly used procedure for coronary revascularization. There are multiple adjuvant anticoagulation strategies available. In this era of cost containment, we performed a comparative effectiveness analysis of clinical outcomes and cost of the major anticoagulant strategies across all types of PCI procedures in a large observational database.. A retrospective, comparative effectiveness analysis of the Premier observational database was conducted to determine the impact of anticoagulant treatment on outcomes. Multiple linear regression and logistic regression models were used to assess the association of initial antithrombotic treatment with outcomes while controlling for other factors.. A total of 458,448 inpatient PCI procedures with known antithrombotic regimen from 299 hospitals between January 1, 2004 and March 31, 2008 were identified. Compared to patients treated with heparin plus glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin was associated with a 41% relative risk reduction (RRR) for inpatient mortality, a 44% RRR for clinically apparent bleeding, and a 37% RRR for any transfusion. Furthermore, treatment with bivalirudin alone resulted in a cost savings of $976 per case. Similar results were seen between bivalirudin and heparin in all end-points. Combined use of both bivalirudin and GPI substantially attenuated the cost benefits demonstrated with bivalirudin alone.. Bivalirudin use was associated with both improved clinical outcomes and decreased hospital costs in this large "real-world" database. To our knowledge, this study is the first to demonstrate the ideal comparative effectiveness end-point of both improved clinical outcomes with decreased costs in PCI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Cost-Benefit Analysis; Female; Hemorrhage; Heparin; Hirudins; Humans; Linear Models; Logistic Models; Male; Middle Aged; Observation; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Young Adult

Topics: Acute Coronary Syndrome; Age Factors; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antithrombins; Feasibility Studies; Female; Hemorrhage; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Prospective Studies; Radial Artery; Recombinant Proteins; Registries; Risk Assessment; Risk Factors; Thrombosis; Time Factors; Treatment Outcome

Major bleeding in the setting of acute coronary syndromes and percutaneous coronary intervention has been associated with increased short-term and long-term risk for adverse cardiac events and mortality. Recent studies on antithrombotic agents in this setting have highlighted their differential impact on ischemic and hemorrhagic complications.. To measure bleeding events consistently, an updated standardized definition has been developed by the Bleeding Academic Research Consortium (BARC) representatives. Additionally, the antithrombin agent bivalirudin has emerged as a frontrunner in the invasive management of acute coronary syndromes because of fewer bleeding complications, lower long-term mortality, and similar efficacy compared with heparin plus a glycoprotein IIb/IIIa inhibitor. The mortality benefit with bivalirudin is most likely correlated with reductions in major bleeding, including in-hospital, access-site, and nonaccess site bleeding, and despite the use of preprocedural unfractionated heparin.. The BARC definition is an improved version of prior bleeding classifications, and will likely play a significant role in comparing different anticoagulation strategies in future clinical trials and registry analyses. Bivalirudin has been shown to reduce bleeding events in a multitude of diverse clinical settings and bleeding definitions, and has become the preferred antithrombotic agent in the setting of acute coronary syndromes.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Phenotype; Recombinant Proteins; Risk Factors; United States

Anticoagulation therapy during percutaneous coronary intervention (PCI) has been the focus of numerous clinical trials. Low-anticoagulant doses have been successfully used in patients undergoing elective PCI, a situation with low-thrombogenic milieu.. The purpose of the study was to evaluate the safety and efficacy of shorter duration of treatment with bivalirudin in patients undergoing elective PCI and receiving optimal antiplatelet therapy.. We compared patients undergoing PCI who received aspirin and clopidogrel loading dose in addition to either conventional bivalirudin dosing (intravenous [IV] bolus of 0.75 + 1.75 mg/kg per h for the duration of PCI; n = 197) or a reduced bivalirudin dose (IV bolus of 0.75 mg/kg; n = 200).. Procedural success was obtained in 100% of cases. The primary end point (in-hospital death, acute myocardial infarction, or need for urgent target vessel revascularization) did not differ between both the groups (6 patients [3%] in the conventional dose group vs 5 patients [2.5%] in the reduced dose group). Major bleeding occurred in 1 patient in the conventional dose group (P = nonsignificant [NS]). Minor bleeding occurred in 4 patients (2%) in the conventional dose group vs 5 patients (2.5%) in the reduced dose group (P = NS) and was mainly due to bleeding at entry site.. In patients undergoing elective PCI, using bivalirudin as a bolus only dosing may be as effective and less costly when compared with bolus followed by an infusion for the duration of the intervention. A larger study is needed to confirm our findings.

Topics: Aged; Alabama; Antithrombins; Aspirin; Clopidogrel; Dose-Response Relationship, Drug; Elective Surgical Procedures; Female; Hemorrhage; Hirudins; Humans; Incidence; Infusions, Intravenous; Injections, Intravenous; Ischemia; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Retrospective Studies; Severity of Illness Index; Thrombosis; Ticlopidine

Fondaparinux is an indirect, Factor Xa inhibitor that requires co-administration of another anticoagulant with anti-Factor IIa activity for percutaneous coronary intervention (PCI) per guideline recommendations. In this setting, the use of bivalirudin, a direct Factor IIa inhibitor, is not well established.. Using the Premier hospital database, we identified 971 patients who underwent elective or urgent PCI after receiving fondaparinux as the initial anticoagulant. They were treated with either bivalirudin ± glycoprotein IIb/IIIa inhibitor (GPI) (Group A=618) or unfractionated heparin (UFH) ± GPI (Group B=353) during PCI. A 2:1 propensity score matching (PSM) process was performed to control for patient and hospital level characteristics. The primary endpoints were to determine in-hospital death, bleeding and post-PCI length of stay (LOS) between treatment groups. After PSM, 512 matched patients were analysed (Group A=348 and Group B=174). In-hospital death was 1.4% in Group A vs. 2.9% in Group B (p=0.26). Clinically apparent bleeding occurred in 4.0% of Group A vs. 9.2% of Group B patients (p<0.02). Clinically apparent bleeding requiring transfusion was lower in Group A patients (0.6% vs. 2.9%; p=0.04). Post-PCI LOS was 1.9 ± 3.8 days for Group A and 2.4 ± 5.8 days for Group B (p=0.36). GPI use during PCI occurred in 9.2% of Group A vs. 44.8% of Group B patients (p<0.0001).. After initial administration of fondaparinux, a bivalirudin-based strategy for PCI is associated with significantly reduced bleeding, with similar mortality and post-PCI LOS when compared with an UFH-based strategy.

Topics: Aged; Anticoagulants; Antithrombins; Drug Therapy, Combination; Female; Follow-Up Studies; Fondaparinux; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Incidence; Length of Stay; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Polysaccharides; Prospective Studies; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Thrombosis; Enoxaparin; Evidence-Based Medicine; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Polysaccharides; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

Patients with central nervous system (CNS) malignancies have a substantial risk for developing both thrombotic and bleeding disorders. The risk of venous thromboembolism (VTE) is substantially higher in these patients, both in the perioperative period and throughout their disease course. Patients with CNS malignancy harbor a latent hypercoagulability, which predisposes to VTE, as do postoperative immobility, hemiparesis, and other factors. The management of VTE in these patients is complex, given the significant morbidity and mortality associated with intratumoral hemorrhage. In the past, the perceived risk of intracranial hemorrhage limited the use of anticoagulation for the management of VTE with many favoring nonpharmacologic methods for prophylaxis and treatment. Inferior vena cava (IVC) filters have since lost favor at many centers given significant complications, which appear to be more frequent in patients with CNS malignancy. Recent studies have demonstrated safe and efficacious use of anticoagulation in these patients with a low incidence of intracranial hemorrhage. Treatment of established VTE is now recommended in this population with many centers favoring low-molecular-weight heparin (LMWH) versus oral warfarin for short- or long-term treatment. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, we recommend LMWH in patients with newly diagnosed VTE and a CNS malignancy.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Bevacizumab; Central Nervous System Neoplasms; Fondaparinux; Glioblastoma; Glioma; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Vena Cava Filters; Venous Thromboembolism; Venous Thrombosis; Warfarin

Bivalirudin, a direct thrombin inhibitor, has been shown to reduce major bleeding and provide a better safety profile compared to unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI) through transfemoral access. Data pertaining to the clinical benefit of bivalirudin compared to UFH monotherapy in patients undergoing transradial PCI are lacking. The present study sought to compare the in-hospital net clinical adverse events, including death, myocardial infarction, target vessel revascularization, and bleeding, for these 2 antithrombotic regimens for all patients at a tertiary care, high-volume radial center. From April 2009 to February 2011, all patients treated with bivalirudin were matched by access site to those receiving UFH. The patients in the bivalirudin group (n = 125) were older (72 ± 13 years vs 66 ± 11 years; p <0.0001), more often had chronic kidney disease (51% vs 30%; p = 0.0012), and more often underwent primary PCI (30% vs 14%, p <0.0037) than the UFH-treated patients (n = 125). A radial approach was used in 71% of both groups. The baseline bleeding risk according to Mehran's score was similar in both groups (14 ± 9 vs 15 ± 8, p = 0.48). In-hospital mortality was 2% in both groups (p = 1.00). No difference in net clinical adverse events or ischemic or bleeding complications was detected between the 2 groups. Bivalirudin reduced both ischemic and bleeding events in femoral-treated patients, but no such clinical benefit was observed in the radial-treated patients. In conclusion, as periprocedural PCI bleeding avoidance strategies have become paramount to optimize the clinical benefit, the interaction between bivalirudin and radial approach deserves additional investigation.

Topics: Aged; Anticoagulants; Antithrombins; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Tertiary Healthcare; Treatment Outcome

The authors sought to describe the association between post-procedural bleeding and long-term recurrent bleeding, major adverse cardiac events (MACE), and mortality among older patients undergoing percutaneous coronary intervention (PCI).. Bleeding complications after PCI are associated with an increased risk for acute morbidity and long-term mortality, but the association of these bleeding complications with other events is unknown.. Patients entered into the National Cardiovascular Data Registry (NCDR) CathPCI Registry (n = 461,311; 946 sites) from January 2004 to December 2008 were linked with claims from the Centers for Medicare & Medicaid Services and grouped according to in-hospital post-PCI bleeding. The association between post-PCI bleeding and 1-, 12-, and 30-month readmission for bleeding, MACE, and all-cause mortality was examined with Cox regression that included patient and procedural characteristics using no bleeding as the reference.. Overall, 3.1% (n = 14,107) of patients experienced post-PCI bleeding. Patients who bled were older, more often female, had more medical comorbidities, less often received bivalirudin, and more often underwent PCI via the femoral approach. After adjustment, bleeding after the index procedure was significantly associated with readmission for bleeding (adjusted hazard ratios [95% confidence interval]: 1 month, 1.54 [1.42 to 1.67]; 12 months, 1.52 [1.40 to 1.66]; 30 months, 1.29 [1.11 to 1.50]), MACE (1 month, 1.11 [1.07 to 1.15]; 12 months, 1.17 [1.13 to 1.21]; 30 months, 1.12 [1.06 to 1.19]) and all-cause mortality (1 month, 1.32 [1.26 to 1.38]; 12 months, 1.33 [1.27 to 1.40]); 30 months, 1.22 [1.15 to 1.30]).. Post-PCI bleeding complications are associated with an increased risk for short- and long-term recurrent bleeding, MACE, and all-cause mortality. These data underscore the prognostic importance of periprocedural bleeding and the need for identifying strategies to reduce long-term bleeding risk among patients undergoing PCI.

Topics: Age Factors; Aged; Aged, 80 and over; Antithrombins; Centers for Medicare and Medicaid Services, U.S.; Chi-Square Distribution; Comorbidity; Female; Hemorrhage; Hirudins; Hospital Mortality; Humans; Kaplan-Meier Estimate; Male; Patient Readmission; Peptide Fragments; Percutaneous Coronary Intervention; Proportional Hazards Models; Recombinant Proteins; Registries; Risk Assessment; Risk Factors; Sex Factors; Time Factors; Treatment Outcome; United States

The impact of a collaborative drug therapy management (CDTM) agreement enabling pharmacist-managed direct thrombin inhibitor (DTI) therapy was evaluated.. A retrospective chart review was conducted to compare selected outcome measures between cohorts of adults who received argatroban or bivalirudin therapy for suspected heparin-induced thrombocytopenia (HIT) before (n = 25) and after (n = 25) the implementation of an institutional DTI protocol under which properly trained and credentialed pharmacists have a primary role in dosing and monitoring DTI infusions. The primary endpoints were the mean time to attainment of activated partial thromboplastin time (aPTT) values in a specified therapeutic range and the proportion of total inpatient treatment time during which aPTT values were in that range. Secondary endpoints included the incidence of major and minor bleeding and the incidence of medication errors.. After implementation of the DTI protocol, therapeutic aPTT values were achieved more rapidly (a mean of 3.4 hours in the postimplementation cohort versus a mean of 7.7 hours in the preimplementation cohort, p = 0.009) and maintained more consistently. Rates of bleeding and overall mortality were similar in the two groups; the frequencies of documented medication errors were 12% and 40% in the postimplementation and preimplementation cohorts, respectively (p = 0.05).. A pharmacist-driven DTI program resulted in improved effectiveness and safety outcomes, as demonstrated by improved attainment of target aPTT values and a decreased frequency of medication errors.

Topics: Adult; Aged; Antithrombins; Arginine; Cohort Studies; Cooperative Behavior; Drug Monitoring; Female; Hemorrhage; Heparin; Hirudins; Humans; Inpatients; Male; Medication Errors; Middle Aged; Outcome Assessment, Health Care; Partial Thromboplastin Time; Peptide Fragments; Pharmacists; Pharmacy Service, Hospital; Pipecolic Acids; Recombinant Proteins; Retrospective Studies; Sulfonamides; Thrombocytopenia; Time Factors

Data from randomized trials has demonstrated the superiority of bivalirudin to glycoprotein IIb/IIIa inhibitors plus heparin in patients undergoing primary percutaneous coronary intervention. Real-world performance of bivalirudin in primary percutaneous coronary intervention and the benefit of bivalirudin over heparin remain unknown in an era of routine dual antiplatelet therapy.. From July 2004 to December 2010, 2317 consecutive patients were indexed in the University of Ottawa Heart Institute ST-segment-elevation myocardial infarction registry. During this period 748 patients received bivalirudin, 699 patients received glycoprotein IIb/IIIa inhibitors, and 676 patients received unfractionated heparin alone. The primary outcome was the rate of noncoronary artery bypass graft related thrombolysis in myocardial infarction major bleeding. Bivalirudin significantly reduced the primary outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors (2.7% versus 7.3%, adjusted OR 2.96, 95% CI: 1.61-5.45, P<0.001) and the composite end point of death, stroke, reinfarction and major bleed (OR 1.66, 95% CI: 1.12-2.45, P=0.01). Compared with heparin alone, a reduction in major bleeds (OR 1.21, 95% CI: 0.60-2.44, P=0.59) or the composite end point (1.05, 95% CI: 0.68-1.63, P=0.83) with bivalirudin could not be demonstrated. Notably, major bleeding was associated with a 5-fold increase in the risk of mortality both in-hospital (3.5% versus 20.6%) and out to 180 days (5.6% versus 25.8%).. Bivalirudin use compared with glycoprotein IIb/IIIa inhibitors plus heparin as an antithrombotic strategy in primary percutaneous coronary intervention results in less major bleeding in contemporary practice. A benefit of bivalirudin over heparin could not be established with this registry and requires additional investigations to either confirm or refute.

Topics: Aged; Anticoagulants; Antithrombins; Chi-Square Distribution; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Hospitals, University; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Ontario; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Propensity Score; Recombinant Proteins; Recurrence; Registries; Risk Factors; Stroke; Thrombosis; Time Factors; Treatment Outcome

Antithrombins are among standard treatment agents for patients with non-ST-segment elevation acute coronary syndromes. We aimed to determine the association between time from emergency department (ED) presentation to treatment with an antithrombin and adverse cardiac events.. The study cohort was a subgroup of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, enrolled from March 1, 2005, to December 5, 2005. The ACUITY trial enrolled patients with moderate- and high-risk non-ST-segment elevation acute coronary syndromes and who were undergoing an early invasive strategy (<72 hours from randomization). All patients received an antithrombin (unfractionated heparin, low-molecular-weight heparin, or bivalirudin), in addition to other agents. A formal ED case report form was introduced in March 2005. Time from presentation to antithrombin initiation was evaluated as a continuous variable in hours. The endpoints were defined as major ischemic events (death, myocardial infarction, unplanned revascularization) or major bleeding within 30 days, or inhospital major bleeding. Logistic regression was used to adjust for demographics, severity of disease, comorbidities, and treatment differences.. Of the 2,722 patients enrolled with an ED case report form, complete time data were available in 2,632 (96%). Median time to antithrombin administration was 4.87 hours (interquartile range 2.67 to 9.83). After multivariable analysis, there was no association of major ischemic events with log time (hours) to antithrombin treatment (adjusted odds ratio [OR] 0.99; 95% confidence interval [CI] 0.97 to 1.01). There was an increase in major bleeding at 30 days and inhospital major bleeding complications with longer log time (hours) to antithrombin initiation (adjusted OR 1.44, 95% CI 1.15 to 1.80; OR 1.43, 95% CI 1.13 to 1.83, respectively).. In this study of patients with non-ST-segment elevation acute coronary syndromes who were undergoing an early invasive management strategy, we were unable to demonstrate an association between adverse ischemic outcomes with the timing of antithrombin administration. However, there was an increase in bleeding outcomes as time to antithrombin administration increased.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Confidence Intervals; Emergency Service, Hospital; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Odds Ratio; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Time Factors

Thrombin-generation and activation of platelets during percutaneous coronary intervention (PCI) play a key role for early thrombotic events. Heparin and bivalirudin are approved anticoagulants for PCI. We examined the specific effects of these anticoagulants on platelet adhesion and aggregation under high shear conditions, and the presence of excess thrombin. To simulate in vivo conditions that may precipitate a bleeding/thrombotic event, we added thrombin in vitro to blood samples from 89 stable patients who had been randomly assigned to receive heparin or bivalirudin for elective PCI and examined thrombin-inducible platelet adhesion and aggregation under high shear conditions. Platelet adhesion increased by 10% of baseline with heparin, but decreased by 20% with bivalirudin (p=0.0047). Thrombin-inducible platelet adhesion and size of aggregates was equally inhibited by heparin and bivalirudin. Thus, under high shear conditions and excessive thrombin generation as they occur in atherosclerotic vascular compartments and acute vascular syndromes, heparin and bivalirudin inhibit thrombin-induced platelet adhesion and aggregation to a similar extent, while they have opposite effects on platelet adhesion in the absence of thrombin.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Adhesiveness; Platelet Aggregation; Recombinant Proteins; Shear Strength; Thrombin; Thrombosis

The majority of coronary angioplasty is done via the femoral artery, with vascular complications being a major adverse event. Bivalirudin has been shown to reduce bleeding complication and improve outcomes. The use of bivalirudin in radial interventions has largely been limited due to the routine use of heparin for the diagnostic procedure. In current practice there is a concern with using the traditional 5,000 Units of heparin during radial sheath insertion and administration of bivalirudin when proceeding to percutaneous coronary intervention (PCI). We describe outcome analysis of the use of low-dose heparin (2,500 Units) with bivalirudin in patients who underwent PCI comparing the adverse outcomes related to bleeding and radial artery occlusion.. The study was an institutional review board-approved retrospective analysis of patients who underwent coronary intervention using the radial approach and the use of bivalirudin over 9-month period. Patients on heparin/low-molecular-weight heparin (LMWH), acute myocardial infarction or allergy to bivalirudin were excluded from the study.. We evaluated 155 patients in the radial and 100 patients in the femoral group. The mean age of the population was 63 ± 11 years (males 68%, weight 88 ± 18 kg) and 66 ± 12 years (males 56%, weight 82 ± 16 kg) in the radial and femoral groups, respectively. Ninety-two percent of the radial and 98% of the femoral cases were elective. The vessels intervened upon were similar in the two groups (left main: 0.65% vs. 2%, left anterior descending artery: 39% vs. 38%, diagonal: 3.8% vs.7%, left circumflex: 16% vs. 21%, obtuse marginal: 7 vs. 11%, right coronary artery: 30% vs.31%, grafts: 1% vs. 5%, in the radial and femoral groups, respectively; p > 0.05). The mean activated clotting time at the end of infusion was 376 ± 47 seconds in the radial and 331 ± 18 seconds in the femoral group. There was only 1 case of documented radial artery occlusion that resolved with 2 weeks of LMWH. Six patients in the radial group and 5 in the femoral group reported minor bruising. There were no reported events related to any major bleeding or transfusions.. Bivalirudin in combination with low-dose heparin (2,500 Units) is safe to use in patients undergoing radial angioplasty with similar event rates to the femoral approach.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Artery Disease; Dose-Response Relationship, Drug; Feasibility Studies; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Radial Artery; Recombinant Proteins; Retrospective Studies; Risk Factors

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Cardiac Catheterization; Coronary Artery Disease; Hemorrhage; Hirudins; Humans; Incidence; Outcome Assessment, Health Care; Peptide Fragments; Radial Artery; Recombinant Proteins

Topics: Acute Coronary Syndrome; Anticoagulants; Clinical Trials as Topic; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk; Stents; Thrombin

Although clopidogrel pretreatment benefits patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes, these benefits are less well established among patients undergoing elective PCI--in particular, when they are treated with the direct thrombin inhibitor, bivalirudin. We used data from the multicenter Evaluation of Drug Eluting stents and ischemic Events registry to assess the association between clopidogrel pretreatment and PCI-related complications among patients undergoing elective PCI with bivalirudin as the antithrombotic regimen. The primary end point was the composite of in-hospital death or myocardial infarction. From January 2005 and December 2007, 4,681 patients underwent elective PCI at 55 United States centers, and 1,913 (41%) received bivalirudin as the planned anticoagulant. Clopidogrel pretreatment was used in 923 patients (48%). The incidence of in-hospital death or myocardial infarction was similar among patients who did and did not receive clopidogrel pretreatment (5.5% vs 5.8%, p = 0.83). This result was unchanged in propensity-adjusted analyses (adjusted odds ratio for pretreatment 0.91, 95% confidence interval 0.60 to 1.39, p = 0.66). Also, no differences were seen in the in-hospital bleeding events (1.0% vs 1.0%, p = 0.94) or 1-year ischemic complications between the 2 treatment groups (7.5% vs 8.3%, p = 0.26). In conclusion, among unselected patients undergoing elective PCI with bivalirudin as the planned anticoagulant, clopidogrel pretreatment was common but was not associated with a reduced risk of ischemic complications.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Antithrombins; Clopidogrel; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Premedication; Recombinant Proteins; Thrombosis; Ticlopidine

This study sought to develop a risk score predictive of bleeding in patients undergoing percutaneous coronary intervention (PCI) and to investigate the impact of bleeding on subsequent mortality.. Bleeding complications after PCI have been independently associated with early and late mortality.. This study represents a patient-level pooled analysis including 17,034 patients undergoing PCI from 3 large, randomized trials of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors, including the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials. We developed a risk score to predict noncoronary artery bypass graft (CABG)-related TIMI (Thrombolysis In Myocardial Infarction) major bleeding and evaluated the impact of various types of bleeding on 1-year mortality.. A non-CABG-related TIMI major bleed occurred within 30 days in 267 patients (1.6%), and death occurred in 497 patients (2.9%) within 1 year. A risk score was developed to predict the bleeding risk of patients undergoing PCI, consisting of 7 variables (serum creatinine, age, sex, presentation, white blood cell count, cigarette smoking, and randomized treatment). The TIMI major bleeding rates increased by bleeding risk score groups: from 0.4% for those in the lowest to 5.8% for those in the highest risk group. Non-CABG-related TIMI major bleeding and the occurrence of myocardial infarction within 30 days were independent predictors of subsequent mortality, with respective hazard ratios of 4.2 and 2.9, each p < 0.001. Ranked in order of severity, TIMI major bleeding, blood transfusion without TIMI bleed, TIMI minor bleeding requiring blood transfusion, and TIMI minor bleeding not requiring blood transfusion were independent predictors of subsequent mortality with hazard ratios of 4.89, 2.91, 2.73, and 1.66, respectively. Isolated hematomas were not predictive of subsequent mortality.. Non-CABG-related bleeding within 30 days is strongly associated with an increased risk of subsequent mortality at 1 year in patients undergoing PCI for all indications. A risk score was established to calculate the bleeding risk for patients undergoing PCI, allowing therapeutic decision making to minimize the incidence of bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Confidence Intervals; Coronary Artery Disease; Drug-Eluting Stents; Female; Health Status Indicators; Hemorrhage; Heparin; Hirudins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Triage

Bivalirudin is widely used as an anticoagulant during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction. However, an increase in acute stent thrombosis rates has been found in the HORIZONS-AMI trial. A prolonged infusion after PCI has been shown to be a safe and effective tool in patients undergoing urgent or elective PCI in the PROBI VIRI study. We examined the effects of prolonged drug infusion after primary PCI. From databases of 5 high-volume centers we compared a group of patients treated with a 4-hour prolonged infusion after PCI to 2 groups treated with a peri-PCI infusion and heparin plus abciximab. The primary study end point was >70% ST-segment resolution within 90 minutes after PCI; secondary end points were partial (>50%) ST-segment resolution within 90 minutes and intrahospital major and minor bleedings on the Acuity scale. The study population consisted of 264 patients undergoing primary PCI who were pretreated with aspirin and clopidogrel. The 3 study groups did not differ significantly by baseline characteristics. The primary end point was achieved in 69.8%, 48.8%, and 69.6% of patients in the prolonged bivalirudin, bivalirudin, and heparin/abciximab groups, respectively (p = 0.048 for prolonged vs standard infusion, p = 0.98 for prolonged infusion vs abciximab). Major bleedings and other secondary study end points were not significantly different among study groups. In conclusion, a strategy of prolonged bivalirudin infusion after primary PCI seems equivalent to a strategy with heparin plus abciximab, with an improvement in standard infusion in obtaining early microvascular reperfusion.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Drug Therapy, Combination; Electrocardiography; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Postoperative Care; Recombinant Proteins

Currently, the wide variety of antithrombotic agents as adjunctive pharmacological therapy for non-ST-segment elevation acute coronary syndromes (ACS) in the setting of contemporary percutaneous coronary intervention (PCI) available for clinical use has made choosing the optimal drug therapy a complex and difficult task. In the stent era, bivalirudin, a semisynthetic direct thrombin inhibitor, has recently been shown to provide similar efficacy with less bleeding compared with unfractionated heparin plus platelet glycoprotein IIb/IIIa inhibitors in ACS patients treated with PCI. Although there are some controversial results and limitations in the studies with bivalirudin, this drug certainly is a plausible option in the treatment of ACS. With current findings in contemporary PCI, there may be a steady increase in the utilization of bivalirudin. On the other hand, in the real world, there may be reinforcement in the sole use of unfractionated heparin confining glycoprotein IIb/IIIa inhibitors and other intravenous antithrombotics to bailout therapy for periprocedural PCI complications in ACS patients.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Blood Coagulation; Combined Modality Therapy; Electrocardiography; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Therapeutic Equivalency

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cohort Studies; Drug Therapy, Combination; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Piperazines; Prasugrel Hydrochloride; Recombinant Proteins; Stents; Thiophenes; Thrombosis; Time Factors

Both ischemic and hemorrhagic complications increase mortality rate in acute coronary syndromes. Their frequency and relative importance vary according to individual patient risk profiles. We sought to develop prognostic models for the risk of myocardial infarction (MI) and major bleeding to assess their impact on risk of death and to examine the manner in which alternative antithrombotic regimens affect these risks in individual patients.. The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial randomized 13 819 patients with acute coronary syndrome to heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. By logistic regression, there were 5 independent predictors of MI within 30 days (n=705; 5.1%) and 8 independent predictors of major bleeding (n=645; 4.7%), only 2 of which were common to both event types. In a covariate-adjusted, time-updated Cox regression model, both MI and major bleeding significantly affected subsequent mortality rate (hazard ratios, 2.7 and 2.9, respectively; both P<0.001). Treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor was associated with a nonsignificant 8% increase in MI and a highly significant 50% decrease in major bleeding. Given the individual patient risk profiles and the fact that bivalirudin prevented approximately 6 major bleeds for each MI that might occur from its use, the estimated reduction in bleeding was greater than the estimated increase in MI by bivalirudin alone rather than heparin plus a glycoprotein IIb/IIIa inhibitor for nearly all patients.. Consideration of the individual patient risk profile for MI and major bleeding and the relative treatment effects of alternative pharmacotherapies permits personalized decision making to optimize therapy of patients with acute coronary syndrome.. clinicaltrials.gov Identifier: NCT00093158.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Factors

Chronic dialysis-dependent patients undergoing percutaneous coronary intervention (PCI) are at a greater risk of bleeding and ischemic events. Bivalirudin has been associated with fewer bleeding complications than unfractionated heparin (UFH) in patients undergoing PCI in various clinical settings. These studies, however, have systematically excluded patients dependent on chronic dialysis. We sought to assess the safety, bleeding rates, and in-hospital outcomes of bivalirudin use compared to UFH use alone in patients requiring dialysis and undergoing PCI. A retrospective analysis of 396 dialysis-dependent patients undergoing PCI from January 2000 to March 2009 was performed. Patients treated with a dose-adjusted bivalirudin regimen (n = 267) were compared to those treated with UFH alone (n = 129). The primary end point of major bleeding (hematocrit decrease > or = 15%, gastrointestinal or intracerebral bleeding) and the composite end point of in-hospital death, nonfatal Q-wave myocardial infarction, and urgent target vessel revascularization were compared between groups. The baseline characteristics were similar between the 2 groups, except for the proportion of men and nonsmokers and body mass index, which were greater in patients treated with bivalirudin. The rate of major bleeding was similar between the bivalirudin and UFH groups (3.4% vs 3.1%, respectively, p = 0.9). The rate of the composite end point (death, Q-wave myocardial infarction, urgent target vessel revascularization) was not significantly different between the 2 groups (1.8% for bivalirudin vs 0.8% for UFH group, p = 0.7). After adjustment, bivalirudin use was not associated with major bleeding (odds ratio 1.23, 95% confidence interval 0.37 to 4.13, p = 0.7). In conclusion, a dose-adjusted bivalirudin anticoagulation regimen for patients requiring chronic dialysis undergoing PCI seems to be as safe and as effective as UFH use alone. These results do not suggest the superiority of bivalirudin over UFH.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Inpatients; Kidney Failure, Chronic; Male; Peptide Fragments; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Diabetes Complications; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Stroke

Topics: Angioplasty; Anticoagulants; Constriction, Pathologic; Hemorrhage; Heparin; Hirudins; Humans; Ischemia; Peptide Fragments; Peripheral Vascular Diseases; Radiography; Recombinant Proteins; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome

To present real-world data to evaluate the safety and effectiveness of bivalirudin, a direct thrombin inhibitor, in an unselected group of patients undergoing percutaneous peripheral interventions (PPI).. Data were extracted from a prospectively collected peripheral vascular registry developed for quality assurance measures at 2 centers. Of 398 consecutive patients (195 men; mean age 69.4+/-11.3 years) who underwent PPI in a 2-year period, 369 (92.7%) received bivalirudin (0.75 mg/kg bolus followed by a 1.75 mg/kg/h infusion) and 29 (7.3%) received unfractionated heparin (UFH). In the bivalirudin sample, critical limb ischemia was present in 28.0% of patients, TASC D lesion in 29.5%, and angiographic thrombus in 7.8% of vessels. Demographic, clinical, procedural, and angiographic variables and in-hospital complications were analyzed. All in-hospital adverse events were independently adjudicated.. Procedural success (<30% residual narrowing) was achieved in 359 (97.3%) patients receiving bivalirudin. Adverse events included stroke (1, 0.3%), acute renal failure (1, 0.3%), major bleeding (3, 0.8%), distal embolization (11, 3.0%), vascular access complications (2, 0.5%), and minor amputation (2, 0.5%).. Bivalirudin had an excellent safety profile in a real-life cohort of patients undergoing PPI, including high-risk patients with critical limb ischemia and TASC D lesions. In-hospital major bleeding and other adverse events were infrequent. A randomized trial of bivalirudin versus UFH is needed to verify these results and establish bivalirudin as a standard anticoagulant in PPI.

Topics: Aged; Aged, 80 and over; Angioplasty; Anticoagulants; Chi-Square Distribution; Constriction, Pathologic; Female; Hemorrhage; Heparin; Hirudins; Humans; Inpatients; Iowa; Ischemia; Logistic Models; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Radiography; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome

Although bivalirudin compared with unfractionated heparin with glycoprotein IIb/IIIa inhibitors reduces bleeding and hospitalization costs in patients undergoing percutaneous coronary intervention (PCI), little is known about the economic impact of bivalirudin versus heparin alone and at what threshold of procedural bleeding risk bivalirudin would be considered cost-effective.. A validated model was used to predict risk of major bleeding for 81,628 National Cardiovascular Data Registry (NCDR) CathPCI Registry patients from 2004 to 2006 who received unfractionated heparin only. Costs were derived from multiple sources including wholesale acquisition costs (for drugs) and single-center data (for PCI-related complications). Based on ISAR-REACT 3, we assumed that bivalirudin would reduce the risk of major bleeding by 33% compared with unfractionated heparin alone. A Markov model was used to estimate lost life expectancy associated with a major bleed. Major bleeding was predicted to occur in 2.2% of patients. Bivalirudin for all patients was estimated to increase costs by $571 per patient, yielding cost-effectiveness ratios of $287,473 per bleeding event averted and $1,173,360 per quality-adjusted life-year gained. Bivalirudin was cost saving for patients with a predicted bleeding risk >20% (0.16% of CathPCI population). At willingness-to-pay thresholds of $50K and $100K per quality-adjusted life-year gained, bivalirudin was cost-effective for patients with a bleeding risk > or = 8% (2.5% patients) and > or = 5% (7.9% patients), respectively.. This decision-analytic modeling study demonstrates that for patients undergoing PCI, substitution of bivalirudin for unfractionated heparin monotherapy is projected to increase costs for virtually all patients and would be considered cost-effective for only a minority of patients with a high bleeding risk. From a policy standpoint, studies such as this, aimed at identifying the appropriate risk threshold for initiating treatment, may help in the development of informed guidelines for the use of expensive therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioplasty; Cost-Benefit Analysis; Decision Support Techniques; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Risk Adjustment

Bleeding complications with percutaneous coronary intervention (PCI) are associated with adverse patient outcomes. The association between the use of bleeding avoidance strategies and post-PCI bleeding as a function of a patient's preprocedural risk of bleeding is unknown.. To describe the use of 2 bleeding avoidance strategies, vascular closure devices and bivalirudin, and associated post-PCI bleeding rates in a nationally representative PCI population.. Analysis of data from 1,522,935 patients undergoing PCI procedures performed at 955 US hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry from January 1, 2004, through September 30, 2008.. Periprocedural bleeding.. Bleeding occurred in 30,654 patients (2%). Manual compression, vascular closure devices, bivalirudin, or vascular closure devices plus bivalirudin were used in 35%, 24%, 23%, and 18% of patients, respectively. Bleeding events were reported in 2.8% of patients who received manual compression, compared with 2.1%, 1.6%, and 0.9% of patients receiving vascular closure devices, bivalirudin, and both strategies, respectively (P < .001). Bleeding rates differed by preprocedural risk assessed with the NCDR bleeding risk model (low risk, 0.72%; intermediate risk, 1.73%; high risk, 4.69%). In high-risk patients, use of both strategies was associated with lower bleeding rates (manual compression, 6.1%; vascular closure devices, 4.6%; bivalirudin, 3.8%; vascular closure devices plus bivalirudin, 2.3%; P < .001). This association persisted following adjustment using a propensity-matched and site-controlled model. Use of both strategies was used least often in high-risk patients (14.4% vs 21.0% in low-risk patients, P < .001).. In a large national PCI registry, vascular closure devices and bivalirudin were associated with significantly lower bleeding rates, particularly among patients at greatest risk for bleeding. However, these strategies were less often used among higher-risk patients.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Embolization, Therapeutic; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Pressure; Recombinant Proteins; Registries; Retrospective Studies; Risk; United States

The aim of this study was to examine the use of and outcomes associated with antithrombotic strategies in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI).. A variety of antithrombotic strategies have been tested in clinical trials for NSTEMI patients treated with PCI.. Antithrombotic strategies for NSTEMI patients undergoing PCI at 217 ACTION (Acute Coronary Treatment and Intervention Outcomes Network) hospitals from January 1, 2007, to December 31, 2007, (n = 11,085) were classified into commonly observed antithrombotic groups: heparin alone (Hep alone; low-molecular-weight heparin or unfractionated heparin), bivalirudin alone (Bival alone), heparin with glycoprotein IIb/IIIa inhibitors (Hep/GPI), and bivalirudin with GPI (Bival/GPI). Baseline characteristics are shown across treatment groups. In addition, unadjusted and adjusted rates of in-hospital major bleeding and death are shown.. The standard strategy used was Hep/GPI (64%), followed by Hep or Bival alone (28%), and Bival/GPI (8%). Patients who received Hep or Bival alone were older with more comorbidities, higher baseline bleeding and mortality risk, and lower peak troponin. Compared with patients who received Hep/GPI , those who received Hep alone and Bival alone had lower rates of major bleeding (adjusted odds ratio [OR]: 0.52; 95% confidence interval [CI]: 0.42 to 0.65; adjusted OR: 0.48; 95% CI: 0.39 to 0.60; respectively), yet only patients who received Bival alone had lower mortality (adjusted OR: 0.39; 95% CI: 0.21 to 0.71).. NSTEMI patients undergoing PCI are more likely to receive Bival or Hep alone when at higher baseline bleeding risk than when at lower baseline bleeding risk. Despite higher baseline risk, those receiving Bival or Hep alone had less bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Chi-Square Distribution; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Registries; Risk Assessment; Risk Factors; Thrombosis; Time Factors; Treatment Outcome; United States

Topics: Angioplasty, Balloon, Coronary; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Risk Factors; Thrombosis; Time Factors; Treatment Outcome

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antithrombins; Eptifibatide; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Patient Selection; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Assessment; Risk Factors; Secondary Prevention; Stents; Time Factors; Treatment Outcome

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Time Factors

This study sought to investigate if the efficacy of bivalirudin monotherapy is similar to heparin plus GP IIb/IIIa inhibition in patients with acute coronary syndromes (ACS) treated with clopidogrel following diagnostic angiography.. Prior trials have demonstrated that peri-procedural bivalirudin therapy confers similar efficacy as heparin plus GP IIb/IIIa inhibitors, while lowering the risk of bleeding complications in ACS patients undergoing percutaneous coronary interventions (PCI). However, the incidence of adverse ischemic events post-PCI appeared to be higher in patients receiving bivalirudin without adequate pretreatment with clopidogrel.. Using the 2004/2005 Cornell Angioplasty Registry, we evaluated 980 consecutive patients undergoing urgent PCI for UA/NSTEMI who were treated with either bivalirudin or UFH plus GP IIb/IIIa inhibitor. We excluded patients who were on chronic clopidogrel therapy or received clopidogrel pretreatment prior to angiography. All patients received a clopidogrel load (≥300-mg dose) immediately before or after the PCI. Long-term all-cause mortality was obtained for 100% of patients, with a mean follow-up of 24.6 ± 7.7 months.. Of the 980 study patients, 461 (47.0%) were treated with bivalirudin and 519 (53.0%) patients received UFH plus GP IIb/IIIa inhibitor. DES were used in 88% of PCI; 45% of patients presented with NSTEMI. The incidence of in-hospital death (0.4% vs. 0.2%, P = 0.604), post-procedural MI (6.9% vs. 5.4%, P = 0.351), and MACE including death, stroke, emergent CABG/PCI, and MI (7.6% vs. 5.8%, P = 0.304) were similar in patients treated with bivalirudin versus UFH plus GP IIb/IIIa inhibitors, respectively. The incidence of in-hospital stent thrombosis was similar (0.7% vs. 0%, P = 0.104), while major (0.9% vs. 2.9%, P = 0.034) and minor bleeding (10.4% vs. 18.9%, P < 0.001) was reduced in the bivalirudin-treated group. By two-years of follow-up, after propensity-score adjusted multivariate Cox regression analysis, there was no significant difference in long-term mortality between the two groups (HR 1.18; 95%CI 0.64-2.19, P = 0.598).. In patients presenting with ACS and receiving clopidogrel treatment after angiography (before or within 30 min of PCI), peri-procedural bivalirudin monotherapy suppresses acute and long-term adverse events to a similar extent as does UFH plus GP IIb/IIIa inhibitors, while significantly lowering the risk of bleeding complications.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antithrombins; Chi-Square Distribution; Clopidogrel; Coronary Angiography; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Diseases; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; New York City; Odds Ratio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Propensity Score; Proportional Hazards Models; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Ticlopidine; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Clopidogrel; Coronary Angiography; Drug Administration Schedule; Drug Therapy, Combination; Heart Diseases; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Risk Factors; Stroke; Ticlopidine; Time Factors; Treatment Outcome

Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI) for stable angina and acute coronary syndrome. This study analyzed the impact of bivalirudin-based anticoagulation strategy versus UFH-based anticoagulation strategy on long-term bleeding complications and major adverse cardiac events in patients undergoing PCI in routine clinical practice. From September 2005 to April 2009, 3,367 consecutive patients who underwent PCI for stable angina or non-ST-segment elevation acute coronary syndrome at Brigham and Women's Hospital were studied. Of these patients, 2,228 patients (66%) received UFH and 1,139 (34%) received bivalirudin. Bleeding complication and major adverse cardiac event rates were compared at discharge, 30 days, and 1 year. In a propensity-score matched analysis, bivalirudin-based anticoagulation strategy was associated with lower bleeding complications at 30 days (7.0% vs 13.7%, p = 0.001) and 1 year (12.7% vs 18.9%, p = 0.013). Major adverse cardiac event rates were not significantly different between groups at discharge, 30 days, and 1 year (6.4% vs 8.3%, p = 0.103; 9.4% vs 10.9%, p = 0.449; 12.1% vs 14.8%, p = 0.235, respectively). There was no difference in all-cause mortality rates between the 2 groups (0.9% vs 0.8%, p = 0.808, at discharge; 1.9% vs 3.6%, p = 0.112, at 30 days; 3.6% vs 5.5%, p = 0.195, at 1 year). In conclusion, in a real-world cohort of patients undergoing PCI, bivalirudin-based anticoagulation strategy is associated with a significant decrease in risk of bleeding complications after 30 days and 1 year compared to a UFH-based anticoagulation strategy with no increase in risk for major adverse cardiac events.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Chi-Square Distribution; Combined Modality Therapy; Female; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Logistic Models; Male; Myocardial Infarction; Peptide Fragments; Propensity Score; Prospective Studies; Recombinant Proteins; Risk Factors

The addition of glycoprotein IIb/IIIa inhibitors (GPIs) to heparin in percutaneous coronary intervention (PCI) procedures has been demonstrated to reduce ischemic complications; however, GPI use is known to increase the risk of bleeding events, which are linked to increased mortality, longer hospital length of stay, greater medical resource utilization, and increased costs. New antithrombotic therapies have the potential to improve clinical outcomes and decrease costs. The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) study of bivalirudin demonstrated significantly reduced clinical event rates (mortality and bleeding) compared with an unfractionated heparin (UFH)+GPI regimen.. The potential clinical and economic value of implementing a bivalirudin-based strategy for ST-segment elevation myocardial infarction (STEMI) patients receiving primary PCI (PPCI) is compared with current UFH+GPI-based practice from a US hospital perspective.. A budget impact model was developed to compare treatment of STEMI patients undergoing PPCI with a bivalirudin- or UFH+GPI-based strategy. Clinical data for the model were derived from the HORIZONS-AMI trial, and included 30-day event rates for major complications (eg, protocol bleeding, Q-wave MI, repeat PCI, and coronary artery bypass graft procedures). United States cost data and clinical practice data were derived from a Premier Perspective™ database analysis and published sources.. Overall, average procedure costs per UFH+GPI-treated patient were $18,561. Treating patients with bivalirudin (incorporating 7.2% provisional GPI use per HORIZONS-AMI) may save $1690 per patient (average procedural cost, $16,872). In extrapolating these benefits to the American College of Cardiology/American Heart Association recommended institutional minimum of 36 PPCIs annually, 1 major bleeding event (3.7%) and 3 minor bleeding events (6.8%) could be averted with use of bivalirudin. In addition, introducing a bivalirudin-based strategy to treat a minimum cohort of 36 STEMI patients would save the hospital budget $60,807 (9%) per year.. Using a bivalirudin-based strategy in STEMI patients undergoing PPCI is associated with favorable clinical and economic outcomes when compared with an UFH+GPI-based strategy in a US hospital setting.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Boston; Budgets; Cost Savings; Drug Costs; Economics, Pharmaceutical; Hemorrhage; Heparin; Hirudins; Hospital Costs; Humans; Models, Econometric; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Reoperation; Risk Factors; Treatment Outcome

The aim of this study was to evaluate anticoagulant use patterns and bleeding risk in a contemporary population of patients with acute coronary syndrome.. Current practice guidelines support the use of unfractionated heparin, low molecular weight heparin, bivalirudin, or fondaparinux in non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Little is known about how these agents are selected in clinical practice.. Between January 2007 and June 2009, data were captured for 72,699 patients with NSTEMI and 48,943 patients with STEMI at 360 U.S. hospitals for the NCDR ACTION Registry-GWTG (National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines). Patients were categorized based on anticoagulant strategy selected during hospitalization and their CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of ACC/AHA [American College of Cardiology/American Heart Association] Guidelines) bleeding risk category.. At least 1 anticoagulant was administered to 66,279 patients (91.2%) with NSTEMI and 46,149 patients (94.3%) with STEMI. Among STEMI patients, unfractionated heparin was most commonly used (66%), followed by bivalirudin (14%) and low molecular weight heparin (8%). In NSTEMI patients, unfractionated heparin was also the most commonly used anticoagulant (42%), followed by low molecular weight heparin (27%) and then bivalirudin (13%). There were significant differences in anticoagulant use by age, risk factors, concomitant medications, and invasive care. There was a 5-fold difference in the rate of bleeding between patients in the lowest and highest CRUSADE bleeding risk groups, which was consistently observed in most anticoagulant groups.. There is a wide variability in the use of anticoagulant regimens with significant differences according to baseline characteristics and concomitant therapies. Major bleeding is common, though a great degree of the variability in the rate of bleeding is largely based on differences in baseline characteristics, comorbidities, and invasive treatment strategies, rather than specific anticoagulant regimens.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Cardiac Catheterization; Chi-Square Distribution; Drug Utilization; Female; Guideline Adherence; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Myocardial Infarction; Outcome and Process Assessment, Health Care; Peptide Fragments; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States

The use of glycoprotein IIb/IIIa inhibitors (GPI) reduces ischemic events in patients undergoing percutaneous coronary intervention (PCI). However, the same properties that confer this benefit lead to an increased bleeding risk. Recent studies have shown a less robust net clinical benefit of GPI in the current era of routine thienopyridine and direct thrombin inhibitor use. To optimize the net clinical benefit of GPI, these agents need to be selectively used in patients most likely to benefit from their anti-ischemic effect, namely patients undergoing PCI for non-ST-segment elevation myocardial infarction, select patients undergoing primary PCI, and select patients undergoing PCI without appropriate pre-loading with a thienopyridine. Moreover, strategies to minimize bleeding should be applied in these patients and include shorter GPI infusions (in some patients), dose adjustments of heparin and GPI, careful access site management with more frequent use of the transradial approach, use of smaller sheaths, and identification of patients at high bleeding risk. This review provides an update of the current literature that supports these measures, an insight on the tailored use of GPI, and a potential direction for future research addressing combined antithrombotic therapies.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Artery Disease; Eptifibatide; Hemorrhage; Hirudins; Humans; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

To retrospectively evaluate the safety and effectiveness of the use of bivalirudin, a direct thrombin antagonist, compared with unfractionated heparin in endovascular aneurysm repair (EVAR).. Between March 1994 and September 2007, 740 consecutive patients (mean age, 75.7 y +/- 7.7; 69 women) underwent elective EVAR for infrarenal abdominal aortic aneurysm. Bivalirudin was used in 98 of these 740 (13.2%) and unfractioned heparin was used in the other 642 (86.8%). Complications were classified according to the Society of Vascular Surgery/International Society for Cardiovascular Surgery criteria. Major bleeding was defined as clinically overt blood loss resulting in a decrease of hemoglobin of more than 3 g/dL, any decrease in hemoglobin of more than 4 g/dL, transfusion of 2 U or more of red blood cells, or intracranial or retroperitoneal hemorrhage.. Grade 1 major complications were observed in 161 of 642 patients (25.2%) in the heparin group and 12 of 98 patients (12.2%) in the bivalirudin group (P = .0046), whereas the incidences of grade 3 major complications were not significantly different between groups (P = .57). The rate of total complications was higher in the heparin group than in the bivalirudin group (247 of 642 [38.5%] vs 21 of 98 [21.4%]; P = .001). Major bleeding occurred in 10 of 98 patients (10.2%) receiving bivalirudin and in 91 of 642 patients (14.2%) receiving heparin (P = .34). One of 21 major complications (4.76%) in the bivalirudin group and 12 of 247 major complications (4.86%) in the heparin group were attributable to thrombosis (P = 1.0).. Bivalirudin is a safe and feasible alternative to unfractionated heparin in patients undergoing EVAR.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Aneurysm, Abdominal; Blood Loss, Surgical; Blood Transfusion; Blood Vessel Prosthesis Implantation; Feasibility Studies; Female; Hemoglobins; Hemorrhage; Heparin; Hirudins; Humans; Male; Peptide Fragments; Postoperative Hemorrhage; Recombinant Proteins; Retrospective Studies; Thrombin; Treatment Outcome

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Drug Hypersensitivity; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; Risk Assessment; Syndrome; Thrombosis

Bivalirudin has been associated with decreased bleeding, with similar rates of ischemia in patients with stable angina, unstable angina, non-ST elevation myocardial infarction and elective percutaneous coronary intervention (PCI). The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial tested whether with primary PCI, bivalirudin--compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor--reduced bleeding and net clinical benefit (bleeding, death, reinfarction, target-vessel revascularization for ischemia or stroke). Bivalirudin reduced major bleeding by 40% (4.9 vs 8.3%; risk ratio [RR]: 0.60; 95% confidence interval [CI]: 0.46-0.77; p < 0.0001) as compared with unfractionated heparin and a IIb/IIIa antagonist. Net adverse clinical events were reduced (9.2 vs 12.1%; RR: 0.76: 95% CI: 0.63-0.92; p = 0.005). Cardiac death and total death at 30 days were reduced with bivalirudin (1.8 vs 2.9%; p = 0.03) and (2.1 vs 3.1%; p = 0.047), and at 12 months (2.1 vs 3.8%; p < 0.005) and (3.4 vs 4.8%; p = 0.029), respectively. Bivalirudin reduced bleeding and net adverse clinical events as well as mortality compared with unfractionated heparin and a glycoprotein IIb/IIIa inhibitor. Bivalirudin is an attractive antithrombotic choice in patients undergoing primary PCI.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Stents

Caring for patients at high risk is inherent to the practice of interventional cardiology. Recognizing high-risk situations, minimizing risk and employing preventive techniques proactively to avoid complications cannot be over-emphasized within this dynamic field. This case demonstrates real-world concerns and decision-making regarding severe bleeding risk, rescue angioplasty, stent thrombosis, appropriate usage of intravascular ultrasound and differences in stent design. Three take-home messages are identified to reduce complications in similar situations.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Thrombosis; Coronary Vessels; Hemorrhage; Hirudins; Humans; Intracranial Hemorrhages; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Risk Factors; Stents; Treatment Outcome; Ultrasonography, Interventional

This study aimed to analyze the impact of replacing heparin with bivalirudin in octogenarians undergoing percutaneous coronary intervention (PCI) on postprocedure hemorrhage and 6-month mortality.. Randomized trials comparing the antithrombin agent bivalirudin with heparin as the intraprocedural anticoagulant identify a reduction in periprocedural bleeding after PCI. Further, the occurrence of such bleeding seems to predict an increased risk of death or myocardial infarction both in-hospital and at long-term follow-up. Importantly, elderly people who are at the greatest risk of post-PCI bleeding complications are underrepresented in these randomized trials.. From 2000 to 2007, 2,766 consecutive patients from our center who were > or = 80 years of age underwent PCI with stent implantation and were included in this analysis. Bivalirudin was used in 1,207 (43.6%) patients and heparin in 1,559 (56.4%). We compared the rates of post-PCI bleeding complications and 6-month mortality.. The overall in-hospital bleeding and 6-month mortality rates were 4.6% and 11.8%, respectively. By multivariate logistic regression and after adjustment by propensity score analysis, bivalirudin was associated with a significant decrease in in-hospital bleedings (HR = 0.41, 95% CI = 0.23-0.73, P = 0.003). By multivariate Cox analysis, bivalirudin was also associated with a significant decrease (HR = 0.6, 95% CI = 0.4-0.9, P = 0.01) and in-hospital bleedings with a significant increase in the 6-month mortality (HR = 2.5, 95% CI = 1.6-3.9, P < 0.001).. This study suggests an important subset for use of bivalirudin in lieu of heparin that will benefit the very elderly.

Topics: Age Factors; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Patient Selection; Peptide Fragments; Proportional Hazards Models; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome

The leech protein hirudin is a potent inhibitor of thrombin, but clinical use of recombinant hirudin is restricted by haemorrhagic risks, and complicated by hirudin's rapid clearance from the circulation. We previously employed albumin fusion to slow hirudin variant 3 (HV3) clearance. In this study, we hypothesized that reconfiguration of the chimera, appending human serum albumin (HSA) to the N-terminus of HV3, with an intervening plasmin cleavage site, would create a slowly cleared, plasmin-activatable HV3. Potential plasmin cleavage sites were screened by expression in Escherichia coli, interposed between glutathione sulfotransferase and HV3 domains. The most reactive sequence (GSGIYR-ITY) was recreated in C-terminally His-tagged albumin fusion protein HSACHV3, expressed in Pichia pastoris yeast and purified by nickel-chelate affinity chromatography. HSACHV3 showed no thrombin inhibitory activity in the absence of plasmin, but liberated active HV3 in a time- and concentration-dependent manner in its presence. In a discontinuous clot assay involving clot-bound thrombin, HSACHV3 assisted clot lysis by limiting clot extension in a tPA- and concentration-dependent manner. Similar results were obtained in plasma at higher concentrations of HSACHV3. The chimeric protein exhibited much slower clearance in mice than unfused HV3, and indistinguishable pharmacokinetics from unfused recombinant HSA. In a mouse tail transection bleeding model, doses of HSACHV3 identical to those of HV3 that elicited a four-fold increase in the volume of shed blood were without effect. Our results suggest that HSACHV3 is a fully latent, plasmin activatable, long-lasting hirudin, of potential benefit in thrombotic disorders resistant to natural or pharmacological clot lysis.

Topics: Animals; Cloning, Molecular; Dose-Response Relationship, Drug; Fibrinolysin; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; Mice; Pichia; Recombinant Fusion Proteins; Serum Albumin; Thrombin; Time Factors

Topics: Animals; Anticoagulants; Antithrombins; Clinical Trials as Topic; Heart Valve Prosthesis; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombin; Thrombocytopenia; Thromboembolism

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Drug Therapy, Combination; Embolism; Eptifibatide; Hemorrhage; Hirudins; Humans; Immunoglobulin Fab Fragments; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Thrombosis; Treatment Outcome

Bivalirudin, a direct thrombin inhibitor, provides similar ischemic outcomes with significantly less major bleeding compared with unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients undergoing percutaneous coronary interventions (PCI). Although the approved labeling for bivalirudin allows for low-dose prolonged postprocedure administration, this practice is not routine. Therefore, we sought to evaluate the safety and efficacy of longer post-PCI infusion.. From our database, we retrospectively compared two groups of patients with acute coronary syndrome undergoing complex PCI, one group treated with UFH+GPI (n = 59) and another with a periprocedural and post-PCI bivalirudin infusion for 4 h (n = 50). Endpoints included periprocedural myocardial infarction (MI), 30-day major adverse cardiac events, and in-hospital major and minor bleeding.. There were no significant differences in the baseline and procedural characteristics of the two groups; most patients (approximately 90%) had complex coronary lesions (the American College of Cardiology/American Heart Association type B2/C). There was no significant difference in the rates of periprocedural MI (11.9 vs. 8.0%, P = NS) or 30-day major adverse cardiac events (8.5 vs. 6.0%, P = NS) among patients treated with UFH+GPI or bivalirudin. However, patients who received bivalirudin had significantly lower rates of minor bleeding (20.3 vs. 4.0%, P<0.05), and a trend toward significantly less major bleeding (8.5 vs. 4.0%, P = 0.07). When we compared the group treated with a prolonged bivalirudin infusion with a historical group treated with peri-PCI-only bivalirudin infusion, we observed in the latter an increased incidence of periprocedural MI and a comparable incidence of bleeding.. A prolonged bivalirudin infusion after urgent PCI seems effective in protecting myocardium without increasing bleeding rates, and represents an attractive alternative to the standard pharmacological treatment of UFH+GPI in the catheterization laboratory.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Cardiovascular Diseases; Drug Administration Schedule; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Risk Assessment; Severity of Illness Index; Time Factors; Treatment Outcome

Topics: Age Factors; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Practice Guidelines as Topic; Recombinant Proteins; Stents; Thrombosis

The aim of this study was to determine the efficacy and safety of bivalirudin versus low-dose unfractionated heparin (UFH) in percutaneous peripheral intervention (PPI).. Anticoagulation strategies used in PPI are based primarily on studies of percutaneous coronary intervention where higher doses of heparin are used usually in combination with a glycoprotein IIb/IIIa inhibitor. There are no studies comparing bivalirudin alone versus low-dose heparin in PPI.. Consecutive patients who underwent PPI at our institution were treated with either bivalirudin or low-dose UFH. Patients were assessed prospectively during index hospital stay for procedural success and bleeding complications. Of 236 patients, 111 were dosed with UFH at 50 U/kg (goal activated clotting time of 180 to 240 s), and 125 were dosed with bivalirudin at 0.75-mg/kg/h bolus followed by a 1.75-mg/kg infusion. Procedural success was defined as <20% post-procedure residual stenosis with no flow-limiting dissections or intravascular thrombus formation and major bleeding as intracranial or retroperitoneal hemorrhage or a fall in hemoglobin >or=5 g/dl. Anticoagulation cost analysis was conducted.. Procedural success and major bleeding rates were similar with bivalirudin versus heparin (98% vs. 99% and 2.4% vs. 0.9%, respectively). There were no differences in minor bleeding, time to ambulation, and length of hospital stay. The hospital cost for bivalirudin was $547 and <$1.22 for heparin (10,000 U). Two activated clotting time levels cost $4.00.. Low-dose UFH is as effective and safe as bivalirudin when used as an anticoagulation strategy in patients undergoing PPI, and low-dose UFH is less costly than bivalirudin. Larger randomized studies are required to further evaluate these findings.

Topics: Aged; Aged, 80 and over; Angioplasty; Anticoagulants; Cost-Benefit Analysis; Drug Costs; Female; Hemorrhage; Heparin; Hirudins; Hospital Costs; Humans; Length of Stay; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Prospective Studies; Recombinant Proteins; Stents; Thrombosis; Time Factors; Treatment Outcome; Walking

Preeclampsia (PE) is a placenta-mediated pregnancy complication that results in high maternal and neonatal mortality and morbidity worldwide. Currently, there is no satisfactory pharmacotherapeutic treatment to stop the PE progression. In this study, we investigated the therapeutic effects of anticoagulant agents, including annexin V, heparin, and a fusion protein of annexin V and hirudin (AND), in a murine PE model induced by intravenous injection of phosphatidylserine/phosphatidylcholine (PS/PC) microvesicles. Compared with the control pregnant animals, the pregnant mice injected with PS/PC presented PE-like symptoms, including elevated systolic blood pressure, proteinuria, and reduction of antithrombin III and blood platelets. However, the PE-like symptoms were significantly alleviated after the PS/PC-injected mice were treated with annexin V, AND, or heparin. Furthermore, fibrin deposition in the placentas in the anticoagulant treated mice was remarkably improved, compared with that in the mice injected with PS/PC alone. The data demonstrate that anticoagulants are effective to prevent the occurrence of PE in the murine model and also suggest that hypercoagulation in the placenta is a contributing factor in the pathogenesis of PE.

Topics: Animals; Annexin A5; Anticoagulants; Antithrombin III; Blood Pressure; Female; Fetal Death; Fetal Weight; Fibrin; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Intestines; Liposomes; Male; Mice; Mice, Inbred ICR; Organ Size; Phosphatidylcholines; Phosphatidylserines; Placenta; Platelet Count; Pre-Eclampsia; Pregnancy; Proteinuria

To resolve the therapeutic dilemma between efficacy of thrombolysis and bleeding risk associated with the use of a combination of thrombolytic and anticoagulant treatments, we created a fusion protein. Staphylokinase was fused to the N-terminus of hirudin using thrombin recognition sequence as linker peptide, resulting in a fusion protein STH. We hypothesised that STH would be cleaved by thrombin at the thrombus site, releasing staphylokinase and hirudin to perform bifunctionally, and attenuating bleeding risk. SDS-PAGE and Western blot analyses indicated that the linker peptide could be specially recognised and cleaved by thrombin. Amidolytic and thromboelastogram assays showed that the N-terminus of hirudin in STH was blocked by staphylokinase and linker peptide, impeding hirudin's anticoagulant activity. Once cleaved, STH displayed 35.7% of the anticoagulant activity of equimolar hirudin and exhibited anticoagulant effects in the fibrin clot lysis assay. Thrombin-binding and fibrin clot lysis assays showed that the C-terminus of hirudin retained its high affinity for thrombin. Moreover, STH showed improved thrombolytic effects and a lower bleeding risk in animals. Thus, STH may have the capacity to perform bifunctionally and release anticoagulant activity in a thrombus-targeted manner in vivo, which may reduce the bleeding risk that often accompanies high thrombolytic efficacy in the treatment of thromboembolic diseases.

Topics: Animals; Base Sequence; Cattle; Disease Models, Animal; DNA Primers; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; In Vitro Techniques; Metalloendopeptidases; Mice; Plasminogen; Rats; Recombinant Fusion Proteins; Thrombelastography; Thrombin; Thromboembolism; Thrombolytic Therapy; Vena Cava, Inferior

This article about hemorrhagic complications of anticoagulant and thrombolytic treatment is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Bleeding is the major complication of anticoagulant and fibrinolytic therapy. The criteria for defining the severity of bleeding vary considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist (VKA)-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that VKA therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0-3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low-molecular-weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute venous thromboembolism. Higher doses of UFH and LMWH are associated with important increases in major bleeding in ischemic stroke. In ST-segment elevation myocardial infarction, addition of LMWH, hirudin, or its derivatives to thrombolytic therapy is associated with a small increase in the risk of major bleeding, whereas treatment with fondaparinux or UFH is associated with a lower risk of bleeding. Thrombolytic therapy increases the risk of major bleeding 1.5-fold to threefold in patients with acute venous thromboembolism, ischemic stroke, or ST-elevation myocardial infarction.

Topics: Anticoagulants; Brain Ischemia; Evidence-Based Medicine; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; International Normalized Ratio; Myocardial Infarction; Polysaccharides; Risk Factors; Severity of Illness Index; Thrombolytic Therapy; Treatment Outcome; Venous Thromboembolism; Vitamin K

For patients undergoing elective percutaneous coronary intervention (PCI), procedural anticoagulation with bivalirudin was previously shown to significantly reduce bleeding complications at the cost of a modest increase in ischemic events compared with unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitors (GPIs). However, the excess bleeding in patients treated with UFH and GPIs may have been caused by excessively high UFH doses and increased activated clotting times. This study sought to determine the bleeding risk of targeted low-dose UFH with GPIs compared with bivalirudin in patients undergoing elective PCI. Of 1,205 patients undergoing elective PCI, 602 underwent PCI with adjunctive UFH and GPIs with the UFH dose targeted to an activated clotting time of approximately 250 seconds, and 603 patients matched for baseline characteristics underwent PCI with bivalirudin. Outcomes were analyzed for major bleeding (hematocrit decrease >15%, gastrointestinal bleed, or major hematoma) and 6-month major adverse cardiac events (death, myocardial infarction, and target-lesion revascularization). The maximum activated clotting time achieved was 261.7 +/- 61.6 seconds in the UFH/GPI group and 355.4 +/- 66.6 in the bivalirudin group (p <0.001). In-hospital major bleeding rates were similar between groups (1.8% UFH/GPI vs 1.7% bivalirudin; p = 0.83), as were transfusion requirements (1.2% UFH/GPI vs 0.5% bivalirudin; p = 0.61). The 6-month major adverse cardiac event rate was also similar between groups (9.5% UFH/GPI vs 9.0% bivalirudin; p = 0.81). In conclusion, there were no significant differences in major bleeding and 6-month major adverse cardiac events for patients undergoing elective PCI treated with targeted low-dose UFH and GPIs compared with those treated with bivalirudin.

Topics: Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

Topics: Acute Disease; Anticoagulants; Arginine; Blood Coagulation; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; International Normalized Ratio; Pipecolic Acids; Platelet Count; Polysaccharides; Recombinant Proteins; Research Design; Sulfonamides; Thrombin; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Warfarin

The purpose of this study was to design and evaluate hirudin (HIR) derivatives with low bleeding risk. In these derivatives, the factor (F) XIa, FXa, and thrombin recognition peptides (EPR, GVYAR, and LGPR, respectively) were linked to the N-terminus of HIR. The intact derivatives have no anticoagulant activity because of the extension of the N-terminus of HIR. After cleavage by the corresponding coagulation factor that occurs on the activation of the coagulation system and in the presence of the thrombus, its activity is released. This limited the anticoagulant activity of these derivatives to the vicinity of the thrombus, and as a result, systemic bleeding complications were avoided. The definite antithrombotic effect and low bleeding parameters of these derivatives were investigated in rat carotid artery and inferior vena cava thrombosis models. In both models, the three derivatives showed significant antithrombotic effects, indicating that anticoagulant activity could be successfully released in vivo. Moreover, the bleeding parameters of these derivatives were lower than that of HIR as indicated by the values of activated partial thromboplastin time (APTT) and thrombin time (TT). To further assess the safety of these derivatives, bleeding time was measured in a mouse tail-cut model. Although the derivatives had obvious effects on bleeding at a dose of 6 mg/kg, the effect of these derivatives on bleeding was significantly weaker than that of HIR at a dose of 1.5 mg/kg. Thus, the benefit-to-risk profiles of the derivatives were superior to that of HIR.

Topics: Animals; Anticoagulants; Bleeding Time; Blood Coagulation; Cloning, Molecular; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Hemorrhage; Hirudins; Male; Mice; Partial Thromboplastin Time; Prodrugs; Rats; Rats, Wistar; Recombinant Fusion Proteins; Risk Assessment; Thrombin Time; Thrombosis; Venous Thrombosis

The current standard of care for anti-thrombotic therapy with primary PCI for acute ST elevation myocardial infarction (STEMI) is aspirin, clopidogrel, unfractionated heparin and platelet glycoprotein IIb/IIIa inhibitors. However, heparin and glycoprotein IIb/IIIa inhibitors are associated with a high incidence of bleeding, and many of the trials documenting benefit with this therapy were performed before the widespread use of stents and clopidogrel. Bivalirudin is a direct thrombin inhibitor which has been found to have similar efficacy with less bleeding compared with heparin plus glycoprotein IIb/IIIa inhibitors when used with elective PCI and with PCI for unstable angina and non-ST elevation myocardial infarction. The HORIZONS trial evaluated bivalirudin compared with unfractionated heparin and IIb/IIIa inhibitors in patients with STEMI treated with primary PCI and found similar MACE (major adverse cardiac events) with less bleeding and a lower incidence of net adverse clinical events (MACE or major bleeding) at 30 days. Mortality at 30 days was also significantly less with bivalirudin. These results make a strong case for the use of bivalirudin with primary PCI in the great majority of patients with STEMI, with the possible exception of patients with cardiogenic shock or stent thrombosis, and patients with a large thrombus burden or no re-flow following PCI. In the latter case, platelet glycoprotein IIb/IIIa inhibitors would be used as a bail-out strategy.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Cardiovascular Diseases; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Patient Selection; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Stents; Thrombin; Thrombosis; Ticlopidine; Treatment Outcome

Topics: Angina, Unstable; Anticoagulants; Cardiac Catheterization; Drug Therapy, Combination; Femoral Artery; Hemorrhage; Hirudins; Humans; Peptide Fragments; Radial Artery; Recombinant Proteins

To compare clinical outcomes and glycoprotein IIb-IIIa inhibitor use in patients undergoing percutaneous coronary intervention (PCI) who received bivalirudin or unfractionated heparin (UFH) in a real-world setting.. Retrospective cohort analysis.. University-affiliated medical center.. One thousand seventy-five adult patients who underwent PCI and received either bivalirudin (539 patients) or UFH (536 patients) from April 1, 2003-April 1, 2004.. Patient data on demographics, comorbidities, laboratory values, and reports of radiologic examinations, cardiac catheterizations, and discharge summaries were obtained. Outcomes evaluated included rates of in-hospital mortality, myocardial infarction, revascularization, and length of stay (LOS), as well as Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) and Thrombosis in Myocardial Infarction (TIMI) bleeding categorization. Bivalirudin use was associated with a significant reduction in TIMI major (5.0% vs 9.7%, p=0.003), REPLACE-2 major (5.4% vs 12.9%, p<0.001), and TIMI minor (1.7% vs 6%, p<0.001) bleeding complications compared with UFH use. Significantly fewer patients in the bivalirudin group received glycoprotein IIb-IIIa inhibitors (27.3% vs 62.7%, p<0.001). Patients receiving bivalirudin had significantly fewer myocardial infarctions after catheterization (10.7% [40/375] vs 18.0% [51/284], p=0.007). No differences were noted in mortality and revascularization rates between groups. A shortened LOS was observed in the bivalirudin group.. This real-world analysis that included high-risk patients provides further evidence that bivalirudin is an attractive alternative to UFH because of a decrease in bleeding events without compromising efficacy.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Cohort Studies; Female; Hemorrhage; Heparin; Hirudins; Hospitals, University; Humans; Length of Stay; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Risk Factors; Thrombosis; Treatment Outcome

The recombinant protein SAK-RGD-K2-Hir is characterized by its fibrin-specific properties of plasminogen activation combined with antithrombin and antiplatelet activities. It was previously shown in our in-vitro studies to be a more potent and faster-acting thrombolytic agent compared with standard r-SAK. In order to document the effects of the thrombolytic potential of SAK-RGD-K2-Hir we examined this protein in an electrically induced carotid artery thrombosis model and stasis-induced venous model in rats. In the arterial thrombosis model, a bolus injection of SAK-RGD-K2-Hir was less effective than rt-PA and r-SAK. However, the most effective in the improvement and maintenance of carotid patency and in arterial thrombus mass reduction was SAK-RGD-K2. In contrast, all r-SAK derivatives reduced venous thrombus weight significantly in comparison to r-SAK and r-Hir. However, the most observable decrease in thrombus weight was obtained after application of recombinant proteins containing the r-Hir. The bleeding time was significantly prolonged in the animals treated with proteins containing r-Hir at a dose of 1.0 mg/kg. There were no observable changes in plasma fibrinogen concentration. In conclusion, our findings show thrombolytic activity in intravenous bolus injection of the novel thrombolytic agent SAK-RGD-K2-Hir in rats. Although this protein compares favourably with r-SAK in rat venous thrombolysis, we were unable to confirm the beneficial effects of SAK-RGD-K2-Hir over r-SAK and rt-PA in the carotid artery thrombolysis model. Furthermore, our results also suggest that SAK-RGD-K2-Hir bears a risk of bleeding, but this may be true for higher doses.

Topics: Animals; Bleeding Time; Blood Coagulation; Carotid Artery Thrombosis; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation; Fibrin; Fibrinolytic Agents; Hemorrhage; Hirudins; Ligation; Male; Metalloendopeptidases; Partial Thromboplastin Time; Rats; Rats, Wistar; Recombinant Fusion Proteins; Thrombin Time; Time Factors; Tissue Plasminogen Activator; Vascular Patency; Venae Cavae; Venous Thrombosis

Anticoagulant therapy plays an important role in current medical practice. The main types of anticoagulant agents are: heparins, hirudins and vitamin K antagonists. None of the drugs used as anticoagulants meet the criteria of an ideal anticoagulant because they have side effects and they interact with other compounds. The main side effect of anticoagulant therapy is bleeding. The choice of a certain anticoagulant is made by the doctor based on the clinical context and also on the desired effect.

Topics: Anticoagulants; Azetidines; Benzylamines; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; International Normalized Ratio; Polysaccharides; Thrombocytopenia; Vitamin K; Warfarin

The objective of this retrospective chart review was to evaluate the safety and feasibility of using the direct thrombin inhibitor bivalirudin as the procedural anticoagulant in patients undergoing percutaneous peripheral intervention (PPI).. Patients with peripheral artery disease are in general a high-risk population that requires safe and reliable anticoagulation with complete thrombin inhibition. Bivalirudin, a direct thrombin inhibitor, has been shown to be as effective as heparin, but with fewer bleeding events in PCI trials, and recent data suggest that bivalirudin may provide the same benefits in PPI.. This was a retrospective chart review of patients who underwent PPI with bivalirudin as the foundation anticoagulant. Bivalirudin was administered as a 0.75 mg per kg bolus, followed by a 1.75 mg per kg per hour infusion for the duration of the procedure. The primary endpoint was procedural success defined as residual stenosis less than or equal to 20%. Ischemic and hemorrhagic events were collected, as well as time-to-sheath removal, ambulation and discharge.. Data were collected for 150 patients. Procedural success was achieved in 98.5%. Ischemic events were low: death (2.0%), myocardial infarction (0.0%), urgent revascularization (0.8%). Major and minor hemorrhage occurred in 4.7% and 2.0% of patients, respectively. Time-to-sheath removal, ambulation and discharge were short.. Bivalirudin provided effective anticoagulation in these generally high-risk patients undergoing PPI. Ischemic and bleeding events were low and comparable to those reported in the literature, suggesting that bivalirudin is safe to use in this population.

Topics: Aged; Angioplasty; Anticoagulants; Antithrombins; Arterial Occlusive Diseases; Feasibility Studies; Female; Hemorrhage; Hirudins; Humans; Incidence; Ischemia; Male; Medical Records; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Urokinase-Type Plasminogen Activator

Outcomes in women undergoing percutaneous coronary intervention (PCI) in the contemporary era are poorly defined. The REPLACE-2 trial demonstrated that bivalirudin with provisional glycoprotein IIb/IIIa (GpIIb-IIIa) blockade is noninferior to heparin with planned GpIIb-IIIa blockade during PCI, with regard to ischemic and bleeding end points.. The aim of this study was to define sex-based clinical ischemic and bleeding outcomes from the REPLACE-2 trial.. A retrospective sex-based subgroup analysis of the REPLACE-2 trial comparing clinical ischemic and inhospital bleeding end points was conducted.. Compared with men in REPLACE-2, women were older, had more diabetes, congestive heart failure and hypertension, and less prior revascularization and myocardial infarction. Female sex was a univariate predictor of death and bleeding complications. Among women treated with either bivalirudin or heparin, there was no significant difference in the individual or composite ischemic end points of death, myocardial infarction, or urgent revascularization at 30 days or 6 months. Protocol-defined major bleeding, minor bleeding, and access site bleeding were less frequent with bivalirudin compared with heparin. Multivariable modeling found no significant interactions between sexes, with the composite ischemic end point, major bleeding, or 1-year mortality.. Women remain at higher risk for poorer outcomes with contemporary PCI, likely because of comorbidities. Bivalirudin with provisional GpIIb-IIIa confers similar protection against ischemic end points compared with heparin and planned GpIIb-IIIa blockade and significantly reduces the inherent bleeding risk of women undergoing contemporary PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Assessment; Sex Factors

The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (+/- SD) dose of 0.06 +/- 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy.

Topics: Adolescent; Adult; Aged; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Thrombocytopenia; Treatment Outcome

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

This study modeled the comparative costs and effectiveness of anticoagulation with bivalirudin alone, heparin alone, and heparin combined with a glycoprotein IIb/IIIa-receptor inhibitor (GPI) in patients undergoing percutaneous coronary intervention (PCI) in Sweden.. GPIs are prescribed for -40% to 50% of patients undergoing PCI in Sweden. However, because treatment practices vary between hospitals, the model analyzed a cohort in which different proportions of patients (0%-100%) would receive a GPI in addition to heparin and the remaining patients would receive heparin monotherapy. This mixed cohort was compared with a cohort treated with bivalirudin. Abciximab was used as the GPI comparator, as this is the only GPI currently approved in Sweden for patients undergoing PCI. Pooled data from 3 studies (REPLACE-2 [second Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischaemia Trial], and EPISTENT [Evaluation of Platelet IIb/IIIa Inhibitor for Stenting]) were used as the source for the probabilities of myocardial infarction (MI), urgent revascularization (UR), major and minor bleeding (Thrombolysis in Myocardial Infarction study definitions), and death. Treatment costs associated with these complications were obtained from 4 Swedish hospitals, and official drug prices were obtained from the Swedish Pharmacopoeia. All costs were presented in 2006 Swedish kronor (SEK). The model was evaluated over a 30-day time frame from the perspective of a Swedish hospital. The modeled patient population was 63 years old, weighed 78 kg, and was 75% male.. Compared with a pattern in which heparin plus a GPI was used in 50% of all PCIs and heparin alone was used in the remaining 50%, bivalirudin treatment was associated with a significant reduction in all complications in the model (P < 0.05), including a mean of 18.2 fewer MIs, 1.6 fewer URs, 15.3 fewer bleeding events, and 1.3 fewer deaths per 1000 treated patients. Bivalirudin therapy also was associated with a significant reduction in total drug and health care costs per patient (SEK -1301; 95% Cl, -1367 to -1229). The benefit of bivalirudin was sensitive to the rate of GPI use: additional reductions in rates of MI, UR, and death were seen at lower rates of GPI use, and additional reductions in rates of bleeding and costs of drugs and health care utilization were seen at higher rates of GPI use.. In this model, anticoagulation with bivalirudin in patients undergoing PCI was cost-effective compared with heparin alone and heparin plus a GPI. In a hypothetical Swedish hospital unit using equal proportions of heparin alone and heparin plus a GPI, a switch to bivalirudin would reduce the risk of both ischemic events and bleeding events, resulting in savings in total drug and health care costs.

Topics: Angioplasty, Balloon, Coronary; Cost-Benefit Analysis; Decision Making; Female; Hemorrhage; Heparin; Hirudins; Humans; Ischemia; Male; Middle Aged; Models, Theoretical; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Randomized Controlled Trials as Topic; Recombinant Proteins; Sweden

A recent large-scale, randomized trial demonstrated the noninferiority of a strategy of bivalirudin with provisional glycoprotein (GP) IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition. There is a paucity of outcome data with bivalirudin use in the setting of real-world experience. We evaluated 6,996 patients who underwent percutaneous coronary intervention between January 2001 and December 2004 to compare early and late outcomes with a bivalirudin-based antithrombotic regimen with those with a heparin-based regimen. Propensity adjustment was performed to correct for baseline differences in patient characteristics. Bivalirudin-based therapy was used in 1,070 patients, heparin only in 801 patients, and heparin plus GP IIb/IIIa inhibitors in 5,125 patients. Compared with patients who received heparin or those who received heparin plus GP IIb/IIIa inhibitors, patients who received bivalirudin had lower incidences of bleeding (blood transfusion rate 1.7% vs 4.0%, p <0.001) and periprocedural myonecrosis (creatine kinase-MB >5 times the upper limit of normal 2.7% vs 4.3%, p = 0.016). Differences in bleeding end points remained significant after adjusting for the propensity to receive bivalirudin, but there was no difference in ischemic events. There was no difference in unadjusted long-term survival rate (log-rank test p = 0.46, total number of deaths 412, mean follow-up 17 months) or in propensity-adjusted long-term survival rate (hazard ratio 1.37, 95% confidence interval 0.90 to 2.08, p = 0.14). Compared with heparin with or without GP IIb/IIIa inhibition, the use of bivalirudin in a large consecutive patient registry at a tertiary care center was associated with fewer bleeding events and no evident increase in the incidence of ischemic complications.

Topics: Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Restenosis; Coronary Stenosis; Creatine Kinase; Creatine Kinase, MB Form; Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Ohio; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Survival Analysis; Treatment Outcome

Chronic kidney disease is associated with an increased risk of ischemic and bleeding complications after percutaneous coronary intervention (PCI). Bivalirudin, a direct thrombin inhibitor, has been shown to reduce adverse bleeding events compared to unfractionated heparin in patients undergoing PCI. However, the effect of diminished renal function on the safety and efficacy of bivalirudin for PCI is unknown. We aimed to test the safety of bivalirudin in routine practice and to assess whether this benefit was influenced by renal function.. The interaction between renal impairment and benefit from bivalirudin was assessed in 115 consecutive patients (age 68.5+/-12.1, 45% female) undergoing PCI. Bivalirudin dosing was adjusted based on renal function. Creatinine clearance (CrCl) was calculated using the Cockroft-Gault formula. The composite endpoints of in-hospital death, myocardial infarction or revascularization and bleeding events were assessed. Overall, these events occurred in 10 (8.7%) patients. Patients with a CrCl<60 ml/min had a significantly increased risk for in-hospital complications (18.6 versus 2.78%, P = 0.011). Univariate analysis for MACE and bleeding were significant for CrCl<60 ml/min OR: 2.54 (95% CI: 1.61-39.7, P = 0.011), age OR: 3.29 (95% CI: 1.07-1.39, P<0.001) and female gender OR: 2.1 (95% CI: 0.036-0.89, P = 0.036). Risk of complications increased with decreasing renal function: 2.7, 14.2, and 37.5% for CrCl of >60, 30-60 or <30 ml/min, respectively, P = 0.002).. Advanced age, renal dysfunction, and female gender remain important risk factors for ischemic and bleeding complications in patients undergoing PCI with bivalirudin.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Comorbidity; Coronary Disease; Creatinine; Female; Hemorrhage; Hirudins; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Peptide Fragments; Prospective Studies; Recombinant Proteins; Risk Factors

Although both argatroban and lepirudin are used for the management of heparin-induced thrombocytopenia (HIT), data comparing these agents are lacking. The objective of this project was to compare the clinical outcomes of lepirudin vs argatroban therapy. Patients who received a direct thrombin inhibitor (DTI) from January 2000 to December 2001 were identified. Medical charts were retrospectively reviewed and relevant data extracted. The primary efficacy outcome was effective anticoagulation and the primary safety outcome was major bleeding. Data were analyzed using the t test and Fisher's exact test. Sixty-one lepirudin patients and 29 argatroban patients received a DTI during the study period. A new diagnosis of HIT was the indication for DTI therapy in 44.8% of argatroban patients and 57.4% of lepirudin patients. Effective anticoagulation was achieved in 77.8% of argatroban patients and 69.5% of lepirudin patients (p = .61). Major bleeding occurred in 10.3% and 11.5% of argatroban and lepirudin patients, respectively (p = 1.0). Argatroban and lepirudin demonstrated comparable safety and efficacy outcomes.

Topics: Aged; Anticoagulants; Arginine; Female; Hemorrhage; Hirudins; Humans; Male; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Thrombin; Treatment Outcome

Major hemorrhage remains a frequent complication of contemporary percutaneous coronary intervention (PCI), regardless of how it is defined. Not only do hemorrhagic complications increase hospital costs, but major hemorrhage is highly predictive of 30-day and 1-year mortality. Use of bivalirudin significantly reduces hemorrhagic complication in PCI.

Topics: Antithrombins; Clinical Trials as Topic; Hemorrhage; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

Despite improvements in techniques and patient management over the past decade, bleeding complications remain an important problem in the practice of interventional cardiology. One approach to minimize bleeding risk is through refinements in technique. Another important strategy involves selection of the antithrombotic regimen. While any discussion of safety must be set against the backdrop of efficacy, this article focuses especially on the bleeding complications associated with various agents, including heparin and other adjunctive therapies (e.g., glycoprotein IIb/IIIa inhibitors, aspirin, clopidogrel), and whether replacements for heparin, such as bivalirudin or enoxaparin, offer any advantages in terms of bleeding risk.

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Aspirin; Clopidogrel; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Immunoglobulin Fab Fragments; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Ticlopidine

Although hirudin is better than heparin at preventing recurrent ischemia in patients with unstable angina, hirudin produces more bleeding. The purpose of this study was to use a rabbit arterial thrombosis prevention and ear bleeding model to determine whether for equivalent efficacy, melagatran, a synthetic direct thrombin inhibitor, is safer than hirudin. A combination of balloon injury and stasis was used to induce thrombosis in the distal aorta, and patency and blood flow were continuously monitored with ultrasonic flow probes. Rabbits were randomized to melagatran (in total doses of 78-313 nmol kg(-1)), hirudin (in total doses of 18-107 nmol kg(-1)), or saline over 90 min. To assess safety, blood loss from standardized ear incisions was measured. Both melagatran and hirudin produced dose-dependent increases in patency and blood flow. At doses that maintained the highest levels of patency, however, melagatran produced 2-3-fold less bleeding than hirudin. Thus, at maximally effective doses, melagatran causes less bleeding than hirudin in this model. These findings raise the possibility that some direct thrombin inhibitors are safer than others.

Topics: Animals; Arteries; Azetidines; Benzylamines; Dose-Response Relationship, Drug; Fibrin; Fibrinolytic Agents; Glycine; Hemorrhage; Hirudin Therapy; Hirudins; Male; Rabbits; Risk Assessment; Thrombin; Thrombosis

Topics: Abciximab; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Angioplasty; Anticoagulants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Fees, Pharmaceutical; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombin

Hirudin, a potent and specific thrombin inhibitor, is a protein of nonhuman origin and therefore potentially immunogenic. The primary objectives of this investigation were to determine the incidence of antihirudin antibodies (ahir-ab) in patients with heparin-induced thrombocytopenia (HIT) who received lepirudin as parenteral anticoagulation and to determine the incidence of death, limb amputation, new thromboembolic complications (TECs), and major hemorrhage in patients who had ahir-ab, compared with patients who were ahir-ab negative. The investigation used data from 2 prospective multicenter studies with the same study protocol, in which HIT patients received 1 of 4 intravenous lepirudin dosage regimens. The treatment duration was 2 to 10 days. Ahir-ab were determined by a newly developed enzyme-linked immunosorbent assay (ELISA). Eighty-seven of 196 evaluable patients (44.4%) had ahir-ab of the IgG class. Development of ahir-ab was dependent on the duration of treatment (ahir-ab-positive patients 18.6 days vs ahir-ab-negative patients 11.8 days; P =.0001). Fewer ahir-ab-positive than ahir-ab-negative patients died (P =.001). Ahir-ab did not cause an increase in limb amputation (P =.765), new TECs (P >.99), or major bleedings (P =.549). In 23 of 51 (45.1%) evaluable patients in whom ahir-ab developed during treatment with lepirudin ( = 12% of all lepirudin treated patients), the ahir-ab enhanced the anticoagulatory effect of lepirudin. Ahir-ab are frequent in patients treated with lepirudin for more than 5 days. Ahir-ab are the first example for a drug-induced immune response causing enhanced activity of a drug. Therefore, during prolonged treatment with lepirudin, anticoagulatory activity should be monitored daily to avoid bleeding complications.

Topics: Amputation, Surgical; Antibodies; Anticoagulants; Extremities; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Immunoglobulin G; Partial Thromboplastin Time; Recombinant Proteins; Thrombocytopenia; Thromboembolism; Time Factors

The novel recombinant hirudin analog CX-397 was investigated with respect to its pharmacological activity and antithrombin profiles in vivo and in vitro. In three different types of thrombosis models in rats, including stasis and thrombin-induced venous, glass surface-activated arterio-venous shunt, and ferric chloride-induced arterial thrombosis models, CX-397 and rHV-1 elicited potent antithrombotic effects, where the minimum effective doses of rHV-1 tended to be higher than those of CX-397 in the arterio-venous shunt and arterial thrombosis models. The hemorrhagic risk of CX-397 in template bleeding in rats was not higher than that of rHV-1, indicating that CX-397 is superior to rHV-1 for treating the platelet-dominant type of thrombosis. However, no differences were detected between CX-397 and rHV-1 in their effects on in vitro coagulation times and thrombin-induced platelet aggregation, suggesting the possibility that some unknown mechanisms other than simple thrombin inhibition are also involved in their antithrombotic actions.

Topics: Amino Acid Sequence; Animals; Arginine; Arterial Occlusive Diseases; Arteriovenous Shunt, Surgical; Chlorides; Drug Evaluation, Preclinical; Ferric Compounds; Fibrinolytic Agents; Glass; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Molecular Sequence Data; Pipecolic Acids; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Serine Proteinase Inhibitors; Sulfonamides; Thrombin; Thrombosis; Vena Cava, Inferior; Venous Thrombosis

Topics: Anticoagulants; Drug Overdose; Heart Failure; Hemodiafiltration; Hemorrhage; Hirudins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Partial Thromboplastin Time; Recombinant Proteins; Renal Dialysis

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Drug Approval; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Multicenter Studies as Topic; Peptide Fragments; Recombinant Proteins; United States; United States Food and Drug Administration

Topics: Antithrombins; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Topics: Fibrinolytic Agents; Hematoma; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Pulmonary Embolism; Recombinant Proteins; Venous Thrombosis

A serious retroperitoneal bleeding occurred in a 56-year-old male patient receiving unfractionated heparin due to multiple pulmonary embolism. After reducing the heparin dose, the patient developed a new pulmonary embolism and a large thrombus in the right atrium. Concomitantly, the platelet count dropped to a value of 29 g/l. Heparin-induced thrombocytopenia (HIT) was confirmed by a functional assay, the heparin-induced platelet activation (HIPA) assay, whereas the results of a platelet factor 4/heparin complex ELISA were repeatedly negative. This indicated that the patient's HIT antibodies were directed towards an antigen other than platelet factor 4/heparin complexes. For treatment of the atrial thrombus, an ultra-low-dose lysis with rt-PA (2 mg/h, intravenously) was administered for a period of 52 h, overlapping with systemic treatment with recombinant hirudin (Lepirudin, Refludan, 0.06-0.14 mg/kg/h intravenously). The aim was to enhance lysis of the thrombus without increasing the haematoma, and at the same time keep the risk of fulminant pulmonary embolism due to thrombus fragmentation as low as possible. The cardiac thrombus disappeared within 48 h, without new signs of pulmonary embolism. Platelet counts normalized within nine days.

Topics: Anticoagulants; Arrhythmias, Cardiac; Autoimmune Diseases; Heart Atria; Heart Diseases; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Phenprocoumon; Plasminogen Activators; Pulmonary Embolism; Recombinant Proteins; Retroperitoneal Space; Thrombocytopenia; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Vena Cava Filters

Recombinant hirudin (rH) is a highly specific thrombin inhibitor which is under clinical investigation for various thrombotic disorders. However, one of its potential risks during clinical use might be hemorrhage, especially when combined with other agents interfering with the coagulation system like antiplatelet or fibrinolytic agents. In this experimental study we investigated whether Haemate, a von Willebrand Factor (vWF) and factor VIII containing product, could correct rH/aspirin induced bleeding in an experimental pig study. Skin bleeding time was evaluated in three open, placebo-controlled, randomized studies following comparable designs. A total of 62 animals were given a short-term infusion of aspirin (20 mg/kg) followed by a three-hour infusion of a high or low dose (0.3 or 0.5 mg/kg/h) of rH. At cessation of rH infusion, animals were allocated to treatment with either Haemate (30 FVIII U/kg) or the recombinant factor VIII, Helixate, which is devoid of vWF. The skin bleeding time (SBT, given as times of baseline) as measured four hours after the start of the rH infusion was defined as the prospective endpoint. In study 1 (low dose rH + Haemate) 4 h SBT was 2.18 (placebo) and 1.61 (Haemate, p = 0.0111). In study No. 2 (high dose rH + Haemate) SBT was 2.58 in placebo and 1.73 in Haemate (p = 0.0001). No significant difference between placebo and treatment were detected in study No. 3 (low dose rH + Helixate). Haemate but not Helixate significantly decreased bleeding time as compared to placebo at termination of the study (7 hours) which was defined as the secondary endpoint. No effect on either aPTT nor rH plasma levels were observed with any of the study drugs. It was concluded that Haemate decreases excess bleeding induced by rH/aspirin treatment without altering rH's anticoagulant effect.

Topics: Animals; Aspirin; Bleeding Time; Factor VIII; Hemorrhage; Hirudins; Infusions, Intravenous; Male; Platelet Aggregation Inhibitors; Protein Engineering; Recombinant Proteins; Skin; Swine; von Willebrand Factor

A canine model of electrolytic injury-induced coronary artery thrombosis and rtPA-induced thrombolysis was used to evaluate the relative antithrombotic efficacy of enoxaparin (a low molecular weight heparin), conventional therapy (heparin or heparin plus aspirin), and hirulog (a direct thrombin inhibitor), when used as adjunctive therapy during thrombolysis. After 60 min of clot aging, adjunctive therapy was begun at doses which elevated APTT approximately 2-fold over baseline. Fifteen minutes after the start of adjunctive therapy, recombinant tissue plasminogen activator (rtPA) was administered (100 microg/kg i.v. bolus + 20 microg/kg/min for 60 min). Adjunctive therapy continued for 1 h after termination of rtPA and blood flow was monitored for two additional hours. Enoxaparin (1 mg/kg i.v. bolus + 30 microg/kg/min, n = 10 for each treatment group) was the only adjunctive treatment that significantly increased the total minutes of flow (143 +/- 25 min out of a possible 240 min, vs 54 +/- 25 min for vehicle, p <0.05) and decreased thrombus mass (6.0 +/- 1.3 mg vs 11.8 +/- 3.2 mg for vehicle). Although hirulog (2 mg/kg i.v. bolus + 40 microg/kg/min) did not significantly increase the minutes of flow (120 +/- 27 min, p <0.06) or decrease thrombus mass (8.7 +/- 1.7 mg) compared to vehicle, these values were not significantly different than those measured in the enoxaparin group. However, the results with hirulog were achieved at the expense of a significantly greater increase in template bleeding time than that measured during enoxaparin treatment. Minutes of flow for heparin (50 U/kg i.v. bolus + 0.6 U/kg/min) and heparin plus aspirin (5 mg/kg i.v. bolus) were 69 +/- 20 and 60 +/- 23 min, respectively; thrombus masses were 8.2 +/- 1.3 and 7.3 +/- 1.0 mg, respectively. In summary, enoxaparin was more effective than conventional therapy in this model in terms of vessel patency and thrombus mass, and was as effective as hirulog, at least at a dose of hirulog that only modestly impaired hemostasis. Therefore, enoxaparin may prove to be a safe and effective alternative agent for adjunctive therapy during thrombolysis with rtPA.

Topics: Adenosine Diphosphate; Animals; Aspirin; Bleeding Time; Collagen; Coronary Thrombosis; Dogs; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Enoxaparin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Hemostasis; Heparin; Hirudin Therapy; Hirudins; Male; Partial Thromboplastin Time; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Prothrombin; Prothrombin Time; Recombinant Proteins; Recurrence; Safety; Thrombin; Thrombolytic Therapy; Tissue Plasminogen Activator

Topics: Anticoagulants; Antithrombin III; Antithrombins; Clinical Trials as Topic; Hemorrhage; Heparin, Low-Molecular-Weight; Hip Prosthesis; Hirudin Therapy; Hirudins; Humans; Postoperative Complications; Recombinant Proteins; Thrombophlebitis; Thrombosis

Hirudin is a potent thrombin inhibitor derived from the leech Hirudo medicinalis salivary gland which has considerable potential for therapeutic use in thrombotic disease. The major risk attendant its use is hemorrhage. This study investigates the hypothesis that the prohemostatic effects of DDAVP infusion can curtail the hemorrhagic effect induced by ongoing hirudin administration. In a randomized and blinded manner, rabbits were exposed to a 15-min intravenous infusion of DDAVP or saline midway through a continuous two-h intravenous infusion of hirudin. Bleeding time was monitored by full thickness ear punctures performed before, during and after hirudin exposure. Hirudin induced a significant hemorrhagic state, manifest as a 7-10-fold prolongation of the primary bleeding time. DDAVP reduced the mean duration of primary bleeding from 10.8 min to 5.9 min (p = 0.001) as well as the number of sites which bled for longer than 6 or 20 min (46% vs 27%, p = 0.002; and 18% vs 5%, p = 0.002, respectively). Although there was no difference in the incidence of spontaneous rebleeding from these sites (44 vs 36%, p = 0.21), rebleeding did not persist as long in animals that received DDAVP (8 vs 16 min, p = 0.005), and fewer sites rebled for longer than 20 min (8 vs 27%, p = 0.027). Results were essentially the same for two different commercial recombinant hirudin preparations. DDAVP appears to attenuate the bleeding caused by continuous hirudin infusion in rabbits and establishes a foundation for clinical assessment in patients.

Topics: Animals; Antithrombins; Deamino Arginine Vasopressin; Double-Blind Method; Drug Therapy, Combination; Hemorrhage; Hemostatics; Hirudins; Infusions, Intravenous; Male; Rabbits; Random Allocation

Hirudin is a peptide of 65 aminoacids extracted from the leech which very specifically inhibits the action of thrombin. Molecular engineering techniques have made it available for therapeutic usage. Experimental data would suggest that hirudin was the drug of choice for the prevention of coronary thrombosis and recurrences, an indication where heparin is not always effective. Despite well organised studies of tolerance and dosage, three large scale clinical trials have had to be interrupted because of a high incidence of severe bleeding complications. The therapeutic margin of hirudin is therefore as low as that of heparin. The initial results of trials using lower doses have not shown hirudin to be effective than heparin in the prevention of critical events in the long term. The reasons for this relative failure are two-fold: either hirudin and molecules with similar modes of action such as Hirulog are less active in vivo than in vitro, possibly due to the fact that they block the activation of the C protein, a powerful natural antithrombotic mechanism, or, the target of hirudin: thrombin, does not play the fundamental role attributed to it in arterial thrombosis. The good results observed with molecules which inhibit platelet aggregation would suggest a dominant role of the platelets.

Topics: Anticoagulants; Antithrombins; Dose-Response Relationship, Drug; Drug Administration Schedule; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Ischemia; Pilot Projects; Treatment Failure

Antithrombotic drugs, such as heparin, have been used in the clinics for a long time. Heparin acts by binding with antithrombin III to form a complex thereby enhancing the activity of antithrombin III to inactivate coagulation factors IIa, IXa, Xa, XIa and XIIa. Hirudin is a new antithrombotic agent and is reported to be much more powerful than heparin on a gravimetric basis. When both are administered systemically, one of the common complications seen is bleeding. Some previous studies have shown that local vascular endothelial concentrations of heparin are 30 to 7500 times greater than those found in the circulating blood. In order to avoid such complications, topical administration of antithrombotic drugs may be an ideal route of administration. The rabbit ear arterial crush-avulsion thrombosis model was used in this study. The animals were divided into five groups: one control group and four treatment groups which received varying concentrations of heparin and hirudin. In the saline control group, the patency rate was 19.23% at 24 hrs and 15.38% at 7 days. A higher patency rate at 7 days was obtained in groups treated with high concentration of heparin and hirudin. ACT, PT and APTT performed on samples drawn one hour after drug administration were within the normal range in both the control and the treatment groups. Scanning electron microscopy revealed the different extent of the clots on the injured intimal surfaces of the vessels in different groups. The results indicate that high concentrations of topically administered heparin or hirudin minimize the systemic complications and maximize the antithrombotic effects.

Topics: Administration, Topical; Anastomosis, Surgical; Animals; Arteries; Drug Synergism; Ear, External; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Male; Microscopy, Electron, Scanning; Microsurgery; Postoperative Complications; Rabbits; Recombinant Proteins; Single-Blind Method; Soft Tissue Injuries; Thrombosis; Vascular Patency; Wounds and Injuries

The infusion of a high dose of recombinant desulphatohirudin HVI (CGP 39393) for 40 min at 30 micrograms/kg/min, resulted in a prolongation of bleeding time in the rat when evaluated using transection of the tail. The prolonged bleeding was evident both immediately, and 30 min after cessation of the infusion of hirudin (CGP 39393). Bleeding time returned to normal after 60 min. The effect of several agents, reported to be successful in reducing bleeding tendencies in man, were evaluated in this rat model. The agents were administered immediately following cessation of the CGP 39393 infusion and their ability to normalize the prolonged bleeding-time, observed at 30 min after cessation of the CGP 39393 infusion, determined. Desmopressin (DDAVP), recombinant factor VIII and Vueffe reduced the bleeding time to the control range but did not exert any significant effects on the bleeding time in rats which did not receive CGP 39393. Epsilon-aminocaproic acid (EACA) and recombinant factor VII were ineffective, at the doses used. In conclusion, DDAVP, factor VIII and Vueffe are effective in reversing the effect of direct thrombin inhibition on bleeding in the rat.

Topics: Aminocaproic Acid; Animals; Bleeding Time; Blood Coagulation; Deamino Arginine Vasopressin; Factor VIIa; Factor VIII; Fibrinolytic Agents; Hemorrhage; Hirudins; Male; Peptides; Rats; Rats, Wistar; Recombinant Proteins

In contrast to thrombin the fibrinogen coagulant effect of the thrombin-like enzyme batroxobin in vitro and in vivo is not inhibited by the specific thrombin inhibitor hirudin. The haemostyptic effect of batroxobin has been studied in rats after bleeding had been induced by corresponding hirudin dosages. Dependent on batroxobin concentration bleeding time was shortened by local application of batroxobin containing solutions. Strong bleeding induced by i.v. injection of 5 mg r-hirudin/kg was stopped almost immediately when a batroxobin concentration of 40 BU/ml was used. Thrombin was less active to stop bleeding after r-hirudin administration than batroxobin.

Topics: Animals; Antifibrinolytic Agents; Batroxobin; Bleeding Time; Drug Interactions; Female; Fibrinolytic Agents; Hemorrhage; Hemostasis; Hirudins; Male; Rats; Rats, Wistar; Recombinant Proteins; Thrombin

The primary bleeding time is prolonged when tested during the infusion of both plasminogen activators and anticoagulants, and such sites frequently exhibit rebleeding after initial hemostatic control. This study describes an animal (rabbit) model which distinguishes fibrinolytic from anticoagulant hemorrhage and further applies the model to the study of hemostatic plugs of increasing age. In this model, rebleeding occurred from hemostatically-stable ear puncture sites induced prior to infusion of streptokinase (SK) or recombinant tissue-plasminogen activator (rt-PA), but not of heparin or hirudin. This distinction was apparent even for lesions induced only 15 minutes prior to the infusion and fibrinolytic bleeding was observed in such lesions induced up to 24 hours earlier. Post-infusion sites bled more quickly than did pre-infusion sites, and there was a gradual decrease in susceptibility of such prior trauma sites for rebleeding, evidenced not only by a lower proportion of sites that rebled, but also by a longer lag time after starting SK or rt-PA before such rebleeding occurred. At the dosages tested, SK showed a trend (not statistically significant) toward more sites that rebled, while rt-PA showed a trend towards a longer duration of rebleeding. Thus, this animal model of rebleeding appears to be unique for fibrinolytic agents and allows for more detailed study of the physiological mechanisms of such bleeding and for a multifaceted comparison of the bleeding potential of plasminogen activators.

Topics: Animals; Anticoagulants; Bleeding Time; Disease Models, Animal; Female; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Hemostasis; Heparin; Hirudins; Male; Rabbits; Recombinant Proteins; Streptokinase; Tissue Plasminogen Activator

The dose- and time-dependent antithrombotic activity of recombinant hirudin (r-hirudin) was examined in a new animal model of venous thrombosis. For the evaluation of the antithrombotic activity of r-hirudin, an occluding thrombus was produced by repeated clamping of the rat jugular vein. The number of clampings necessary to induce thrombosis served as a measure of antithrombotic activity. The gradual reduction of blood flow was registered by Doppler sonography. In order to estimate the relative antithrombotic activity of r-hirudin, its potency in this model was compared with other antithrombotic substances. r-Hirudin proved to be less potent than heparin after intravenous administration. Its half-life after subcutaneous administration was relatively short; however, the antithrombotic potency after subcutaneous administration was comparable to that of heparin.

Topics: Animals; Blood Coagulation Tests; Constriction; Disaccharides; Fibrinolytic Agents; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Injections, Intravenous; Injections, Subcutaneous; Jugular Veins; Male; Rats; Rats, Inbred Strains; Recombinant Proteins; Tail; Thrombolytic Therapy; Thrombosis

The in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin) were studied in the activated partial thromboplastin time (APTT) and the thrombin generation test systems. In the APTT, at concentrations below 5 micrograms/ml, r-hirudin showed a dose-response curve. At concentrations above 5 micrograms/ml, the plasma became unclottable, but in the thrombin generation test, at least 10 micrograms/ml of r-hirudin was required for full inhibition of thrombin generation. The antithrombotic effect was assessed using a rabbit venous stasis model; 150 micrograms/kg r-hirudin completely prevented thrombus formation at 10 and 20 min stasis. At this full antithrombotic dose, the mean bleeding time ratio measured in a rabbit ear template model, was not prolonged over control values. At higher doses, the bleeding time ratios were higher than those observed for the same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.

Topics: Animals; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; In Vitro Techniques; Partial Thromboplastin Time; Rabbits; Recombinant Proteins; Thrombin Time; Thrombophlebitis

The usability of recombinant hirudin as anticoagulant agent in haemodialysis was studied in nephrectomized dogs. To this end, we examined the capability of recombinant hirudin to penetrate the membranes of different capillary dialyzers used. Furthermore we investigated the pharmacokinetic behaviour of recombinant hirudin in nephrectomized dogs as well as its capability to prevent the activation of the clotting system and fibrin deposition during haemodialysis. The present results evidence the efficiency of recombinant hirudin in preventing thrombus formation in experimental haemodialysis and hence its suitability as anticoagulant in such extracorporeal circulation.

Topics: Animals; Blood Coagulation Tests; Blood Pressure; Dogs; Female; Fibrinogen; Hemorrhage; Heparin; Hirudins; Male; Nephrectomy; Platelet Count; Recombinant Proteins; Renal Dialysis

The bite of the medicinal leech bleeds for many hours. For decades it has been assumed that the remarkably prolonged bleeding time of a leech bite wound is due to hirudin, a specific anti-thrombin secreted by the leech during feeding. By measuring haematological parameters of blood oozing from a leech bite wound on 15 different occasions in 7 human volunteers, we demonstrate that the hirudin-sensitive coagulation parameters, including thrombin-induced platelet aggregation, are prolonged for only 15 min, after which they return to normal. This suggests that excess hirudin secreted by the leech is washed out during this period. However, bleeding from the leech bite wound persists for a mean of 10 h. Platelets in smears of exuding blood show no evidence of spontaneous aggregation, but in vitro platelet aggregation can be induced by exogenous collagen at any time. In view of sustained bleeding in the apparent absence of hirudin, attention is focussed onto an unsuspected factor or factors which may better explain the prolonged bleeding phenomenon.

Topics: Animals; Bites and Stings; Bleeding Time; Female; Hemorrhage; Hirudins; Humans; Leeches; Male; Platelet Aggregation; Platelet Function Tests; Time Factors

Haemorrhagic effects of the naturally occurring thrombin inhibitor hirudin measured by the determination of bleeding time were compared with its antithrombotic actions in different models of experimental thrombosis. In mice and rats intravenous administration of hirudin caused a plasma concentration-dependent prolongation of bleeding time after transection of the tail tip and standardized incision of the tail, respectively. In rats intravenous infusion of hirudin prevented the formation of stasis-induced venous thrombosis of the jugular vein and the occurrence of thrombotic occlusion of the carotid artery after electrically induced damage of the vessel wall. Comparison of the haemorrhagic action of hirudin with its antithrombotic effectiveness showed that it caused haemorrhagic side effects only at plasma concentrations which are not required for the antithrombotic effects.

Topics: Animals; Female; Fibrinolytic Agents; Hemorrhage; Hirudins; Injections, Intravenous; Male; Mice; Mice, Inbred Strains; Rats; Rats, Inbred Strains; Thrombin; Thrombin Time

The pharmacological properties of a genetically engineered recombinant hirudin (r-hirudin) were studied in animal experiments. r-Hirudin proved to be a well tolerated substance. I.v. injection of up to 200 mg/kg did not lead to perceptible functional or morphological changes. There were no treatment-related effects on the cardiovascular system of dogs and rats after administration of up to 10 mg/kg. After long-term treatment (4 weeks, 1.0 mg/kg daily), no r-hirudin-related histopathological, haematological or biochemical changes could be found. Formation of antibodies was not detectable. Absorption, distribution, and elimination of r-hirudin were studied in dogs and rats. Pharmacokinetics could be best described by an open two-compartment model with first-order kinetics. After i.v. injection in dogs, r-hirudin is distributed into the extracellular space and eliminated through the kidneys in active form by glomerular filtration. After i.v. administration, a half-life of about 1 h was estimated; s.c. administration prolonged the apparent half-life. Pulmonary absorption was shown. Enteral absorption, placental transfer as well as transfer through the fetal integument were very low. r-Hirudin did not pass the blood-brain barrier. The efficacy of r-hirudin in preventing both venous and arterial thrombosis, vascular shunt occlusion or disseminated intravascular coagulation was demonstrated in rats. Depending on the dose, r-hirudin was able to prevent or reduce stasis-induced venous thrombosis, prolong the patency of an extracorporeal arteriovenous shunt, reduce the incidence of arterial thrombosis caused by vascular wall lesions as well as of microthrombosis induced by thrombin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Behavior; Body Weight; Dogs; Female; Fibrinolytic Agents; Hemodynamics; Hemorrhage; Hirudins; Iodine Radioisotopes; Male; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Nephrectomy; Pregnancy; Rabbits; Rats; Rats, Inbred Strains; Recombinant Proteins; Respiration

Topics: Creatinine; Hemorrhage; Hirudins; Humans; Postoperative Complications; Uremia