bivalirudin and Myocardial-Infarction

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

 Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed..  To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin..  We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin..  From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin)..  We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results.

Topics: Algorithms; Anticoagulants; Data Interpretation, Statistical; Databases, Factual; Drug Administration Schedule; Heparin; Hirudins; Humans; Medical Informatics; Myocardial Infarction; Outcome Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk; Treatment Outcome

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

Although the current practice guidelines recommend using both heparin and bivalirudin for percutaneous coronary interventions (PCI), the research data are ambiguous.. The aim of the study was to compare the impact of bivalirudin and heparin on major clinical endpoints in PCI patients with particular emphasis on periprocedural stent thrombosis.. A total of 18 randomised clinical trials involving 41,752 subjects were included. The endpoints comprised: net adverse clinical event (NACE: death, myocardial infarction [MI], unscheduled revascularisation, major bleeding), major adverse cardiovascular event (MACE: death, MI, or stroke), and acute/subacute stent thrombosis (ST). A subanalysis for planned and provisional glycoprotein IIb/IIIa inhibitor (GPI) use with heparin was performed. Results were presented as risk ratios (RR) and 95% confidence intervals (CI).. Bivalirudin significantly reduced NACE risk (RR 0.85, 95% CI 0.76-0.96) and increased the incidence of MI (RR 1.09, 95% CI 1.01-1.18), ST (RR 1.50, 95% CI 1.13-1.99), and MACEs (RR 1.06, 95% CI 0.99-1.13). Comparing to heparin with provisional or planned GPI use, there was higher risk of acute ST with bivalirudin (RR 2.14, 95% CI 1.01-4.56 and RR 5.53, 95% CI 2.32-13.18, respectively). Comparing to heparin and provisional GPIs, bivalirudin failed to reduce NACEs and major bleeding. However, it decreased rates of NACEs (RR 0.81, 95% CI 0.69-0.96) and major bleeding (RR 0.64, 95% CI 0.48-0.85) compared with heparin and planned GPI use.. The advantages of bivalirudin are undoubtedly related to GPI use in the heparin arms. Bivalirudin-based regimens are more beneficial when compared with heparin and planned GPI use in terms of NACE and major bleedings; this was not observed when compared to heparin and provisional GPI use. Regardless of adjunctive GPI use, stent thrombosis episodes were significantly more common in bivalirudin-treated subjects. Therefore, the safety and economic issues may urge revision of this aspect of current clinical practice and guidelines.

Topics: Adult; Anticoagulants; Antithrombins; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins

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

Despite several randomized controlled trials and meta-analyses, the ideal anticoagulant for patients undergoing primary percutaneous coronary intervention (PCI) remains controversial. We performed an updated meta-analysis including recently reported randomized clinical trials that compare bivalirudin and heparin with or without provisional administration of a glycoprotein IIb/IIIa inhibitor (GPI) for primary PCI.. Scientific databases and Web sites were searched for randomized clinical trials. Data from 6 trials involving 14,095 patients were included. The pooled risk ratios (RRs) were calculated using random-effects models. Moderator analyses examined the impact of routine use of GPI, radial access, and P2Y12 inhibitors on safety outcomes. At 30 days, patients receiving bivalirudin had rates of major adverse cardiac events similar to those receiving heparin with or without provisional GPI (RR 1.02, 95% CI 0.87-1.19, P = .800), myocardial infarction (RR 1.41, 95% CI 0.94-2.11, P = .089), target vessel revascularization (RR 1.37, 95% CI 0.91-2.04, P = .122), and net adverse clinical events (RR 0.81, 95% CI 0.64-1.01, P = .069). However, bivalirudin use decreased the risk of all-cause mortality (RR 0.81, 95% CI 0.67-0.99, P = .041) and cardiac mortality (RR 0.68, 95% CI 0.51-0.91, P = .009) at 30 days, There were higher rates of acute stent thrombosis (RR 3.31, 95% CI 1.79-6.10, P < .001) in patients receiving bivalirudin. Bivalirudin use also decreased the risk of major bleeding at 30 days by 37% (RR 0.63, 95% CI 0.44-0.90, P = .012), but bleeding risk varied depending on routine GPI use with heparin (RR 0.44, 95% CI 0.23-0.81, P = .009) vs bailout (RR 0.73, 95% CI 0.42-1.25, P = .252), predominantly radial access (RR 0.54, 95% CI 0.25-1.15, P = .114) vs non-radial access (RR 0.60, 95% CI 0.36-0.99, P = .049), and second-generation P2Y12 inhibitor use with bivalirudin (RR 0.70, 95% CI 0.40-1.24, P = .226) vs clopidogrel use (RR 0.39, 95% CI 0.18-0.85, P = .018).. In primary PCI, relative to heparin, bivalirudin reduces the risk for all-cause mortality, cardiac mortality, and major bleeding but yields similar rates of major adverse cardiac event and net adverse clinical event at 30 days. However, the benefit of a reduction in bleeding with bivalirudin appears to be modulated by the concurrent administration of second-generation P2Y12 inhibitors with bivalirudin, using radial access, and avoiding routine GPI use with heparin.

Topics: Anticoagulants; Antithrombins; Global Health; Heparin; Hirudins; Humans; Incidence; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Recombinant Proteins; Survival Rate

Radial access for percutaneous coronary intervention (PCI) has been shown to be associated with better outcomes compared with femoral access. However, it is unknown whether bivalirudin would offer any further benefit when compared with unfractionated heparin for PCI with radial access.. A systematic search of electronic databases was conducted for randomized trials comparing bivalirudin with unfractionated heparin in patients undergoing PCI with a radial access. The primary safety outcome was major bleeding, while the primary efficacy outcome was major adverse cardiac events (MACE). Random effects overall risk ratios (RR) were calculated using DerSimonian and Laird model.. A total of 8044 patients from 5 trials were included in the final analysis. The incidence of major bleeding was 1.8% in the bivalirudin group versus 2.2% in the unfractionated heparin group (RR 0.72, 95% CI 0.44-1.17, p=0.18). Meta-regression analysis demonstrated that the risk of major bleeding was lower with bivalirudin when higher doses of unfractionated heparin were used in the control arm (p=0.02). The incidence of MACE was 8.5% in the bivalirudin group versus 7.5% in the unfractionated heparin group (RR 1.15, 95% CI 0.81-1.64, p=0.44). There were no significant differences in the incidence of all-cause mortality, and net adverse clinical events between both groups (RR 0.98, 95% CI 0.70-1.36, p=0.89; and RR 0.79, 95% C I0.60-1.03, p=0.08, respectively).. Bivalirudin might not be associated with better outcomes, when compared with unfractionated heparin in patients undergoing PCI with radial access.

Topics: Blood Loss, Surgical; Heparin; Hirudins; Humans; Incidence; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Radius; Randomized Controlled Trials as Topic; Recombinant Proteins; Regression Analysis; 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

In the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) treated with bivalirudin had lower bleeding and mortality rates, but higher acute stent thrombosis rates compared with heparin + a glycoprotein IIb/IIIa inhibitor (GPI). Subsequent changes in primary PCI, including the use of potent P2Y12 inhibitors, frequent radial intervention, and pre-hospital medication administration, were incorporated into the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned 2,218 patients to bivalirudin versus heparin ± GPI before primary PCI.. The goal of this study was to examine the outcomes of procedural anticoagulation with bivalirudin versus heparin ± GPI for primary PCI, given the evolution in primary PCI.. Databases from HORIZONS-AMI and EUROMAX were pooled for patient-level analysis. The Breslow-Day test evaluated heterogeneity between trials.. A total of 5,800 patients were randomized to bivalirudin (n = 2,889) or heparin ± GPI (n = 2,911). The radial approach was used in 21.3% of patients, prasugrel/ticagrelor was used in 18.1% of patients, and GPI was used in 84.8% of the control group. Bivalirudin compared with heparin ± GPI resulted in reduced 30-day rates of major bleeding (4.2% vs. 7.8%; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to 0.66; p < 0.0001), thrombocytopenia (1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; p = 0.0002), and cardiac mortality (2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; p = 0.03), with nonsignificantly different rates of reinfarction, ischemia-driven revascularization, stroke, and all-cause mortality. Bivalirudin resulted in increased acute (<24 h) stent thrombosis rates (1.2% vs. 0.2%; RR: 6.04; 95% CI: 2.55 to 14.31; p < 0.0001), with nonsignificantly different rates of subacute stent thrombosis. Composite net adverse clinical events were lower with bivalirudin (8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; p < 0.0001). There was no significant heterogeneity between the 2 trials for these outcomes, and results were consistent across major subgroups.. Despite increased acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical outcomes, with significant reductions in major bleeding, thrombocytopenia, and transfusions compared with heparin ± GPI, results that were consistent with evolution in PCI technique and pharmacotherapy. (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723).

Topics: Aged; Antithrombins; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

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

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

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

The aim of this study was to assess the impact of bivalirudin, as compared to unfractionated heparin, on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).. A meta-analysis of randomized trials comparing bivalirudin versus heparin in patients with STEMI undergoing primary percutaneous coronary intervention was performed. Three randomised trials enrolling 7,612 patients were included. Analysis was by intention to treat.. At 30 days, bivalirudin, as compared to heparin, was associated with a similar risk of all-cause mortality (3.03% vs. 3.38%, odds ratio (OR) 0.90, 95% confidence intervals (CI) [0.63 to 1.29], P = 0.57). Bivalirudin significantly increased the risk of definite (2.39% vs. 1.06%, OR 2.49, 95% CI [1.30 to 4.76], P = 0.006); definite or probable (2.55% vs. 1.35%, OR 2.26, 95% CI [1.07 to 4.79], P = 0.03), and acute stent thrombosis (1.69% vs. 0.39%, OR 4.34, 95% CI [2.30 to 8.16], P < 0.001); leading to nonsignificantly higher reinfarction rates (2.0% vs. 1.31%, OR 1.72, 95% CI [0.89 to 3.35], P = 0.11), and to a significantly increased risk of ischemia driven revascularization (2.50% vs. 1.52%, OR 1.80, 95% CI [1.02 to 3.18], P = 0.04) at 30 days. No firm evidence for a reduction in major bleeding associated with bivalirudin use was found (3.93% vs. 6.39%, OR 0.63, 95% CI [0.39 to 1.04], P = 0.07).. In patients with STEMI, bivalirudin, as compared to heparin, increases the risk of stent thrombosis and ischemia driven repeat revascularization at 30 days. There is no strong evidence that bivalirudin significantly reduces major bleeding at 30 days. Bivalirudin does not have an effect on all-cause mortality at 30 days.

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

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

The safety and effectiveness of using the direct thrombin inhibitor bivalirudin during transcatheter coronary interventional procedures remains uncertain.This study aimed to systematically assess anticoagulation with bivalirudin alone or bivalirudin plus glycoprotein (GP) IIb/IIIa inhibitors (bivalirudin-based anticoagulant therapy) in patients undergoing percutaneous coronary intervention (PCI) procedures by a meta-analysis of randomized controlled trials (RCTs).Systematical searches of the MEDLINE, EMBASE, and Cochrane databases were conducted. RCTs comparing bivalirudin-based anticoagulant therapy with a comparable heparin therapy in patients undergoing PCI were eligible. Risk ratios (RRs) with 95% confidence intervals (CIs) served as summary statistics.A total of 38,096 patients from 17 RCTs were randomized to the bivalirudin group (n = 18,878) or heparin group (n = 19,218) in the meta-analysis. No significant differences in death, myocardial infarction or reinfarction, ischemia-driven revascularization, or in-stent thrombosis were observed between the 2 groups (all P > 0.05). Notably, bivalirudin-based therapy showed a highly significant 34% decrease in the incidence of major bleeding (RR = 0.66; 95% CI 0.54-0.81; P < 0.001) and a 28% reduction in the need for blood transfusion (RR = 0.72; 95% CI 0.56-0.91; P < 0.01). Meta-regression analyses demonstrated that additional administration of GP IIb/IIIa receptor inhibitors (P = 0.01), especially eptifibatide (P = 0.001) and tirofiban (P = 0.002), was likely to increase the major bleeding risk associated with bivalirudin.Bivalirudin, in comparison to heparin, is associated with a markedly lower risk of major bleeding, and the additional use of GP IIb/IIIa inhibitors may weaken this benefit.

Topics: Antithrombins; Cardiac Catheterization; Eptifibatide; Hirudins; Humans; Integrin alpha2; Myocardial Infarction; Peptide Fragments; Peptides; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Tirofiban; Treatment Outcome; Tyrosine

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

This study sought to investigate the relative safety and efficacy of bivalirudin versus heparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI) and in those with ST-segment elevation myocardial infarction (STEMI). The safety of bivalirudin in PCI, particularly in patients with STEMI, continues to be debated. We searched the on-line databases for randomized controlled trials of bivalirudin versus heparin plus GP IIb/IIIa inhibitors. Data on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes at 30 days were extracted. A total of 19,856 PCI patients included in 7 randomized trials and 5,820 patients with STEMI included in 2 randomized trials were separately analyzed. At 30 days, bivalirudin use in patients undergoing PCI resulted in similar rates of death, myocardial infarction, repeat revascularization, and stent thrombosis. In patients with STEMI, bivalirudin use resulted in decreased cardiac mortality (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.50 to 0.97, p=0.03) compared with heparin plus GP IIb/IIIa inhibitors but an increase in definite stent thrombosis at 30 days (RR 1.88, 95% CI 1.09 to 3.24, p=0.02) driven by an increase in acute stent thrombosis (RR 5.48, 95% CI 2.30 to 13.07, p=0.0001). Bivalirudin use was associated with a decrease in Thrombolysis In Myocardial Infarction (TIMI) major (RR 0.58, 95% CI 0.46 to 0.74, p<0.0001) and TIMI minor (RR 0.55, 95% CI 0.48 to 0.63, p<0.0001) bleeding rates in PCI patients as well as in a subgroup of patients with STEMI. In conclusion, in PCI patients anticoagulation with bivalirudin results in similar ischemic adverse events and a reduction in TIMI major and minor bleeding at 30 days compared with heparin plus GP IIb/IIIa inhibitors. In patients with STEMI, bivalirudin use is associated with a reduction in TIMI major and minor bleeding and fewer deaths from cardiac causes but an increase in acute and 30-day definite stent thrombosis.

Topics: Anticoagulants; Antithrombins; Drug Therapy, Combination; Electrocardiography; Fibrinolytic Agents; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Preoperative Care; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

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

Providing optimal care to patients with ST-segment elevated myocardial infarction is challenging. If a patient experiences chest pain and calls the emergency number, a cascade of actions is initiated that should lead to a diagnosis, start of treatment and reperfusion of the infarcted myocardium. This should all happen within 90 min after first medical contact, irrespective of the location of the patient or the time of day. The complex organization that is needed to achieve this goal in every ST-segment elevated myocardial infarction patient accounts for a fascinating interplay between prehospital and in-hospital care, in a situation when every minute counts. State-of-the-art care should be provided according to the latest insights and guidelines.

Topics: Antithrombins; Clopidogrel; Electrocardiography; Emergency Medical Services; Hirudins; Humans; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Registries; Survival Analysis; Thrombolytic Therapy; Ticlopidine; Time Factors; Treatment Outcome

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer (The Medicines Company) of bivalirudin to submit evidence for its clinical and cost effectiveness within its licensed indication for the treatment of adults with ST-segment elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention (PPCI), as part of NICE's single technology appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG), which produced a review of the evidence within the manufacturer's submission to NICE. This article describes the manufacturer's submission, the ERG review and NICE's subsequent decisions. The main evidence was derived from one randomized controlled trial (RCT) of STEMI patients intended for PPCI, comparing bivalirudin with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors (GPIs). Bivalirudin was associated with a significant reduction in cardiac mortality at 30 days (p = 0.03) and at 1-year follow-up (p = 0.005), and a significant reduction in major bleeding at 30 days (p < 0.001) and 1 year (p < 0.0001), compared with heparin plus GPI. Stent thrombosis up to 24 hours following PPCI was significantly (p < 0.001) more common with bivalirudin. However, there was no significant treatment effect for stent thrombosis from 1 to 30 days (p = 0.28), or at 1-year follow-up (p = 0.53). There were no significant treatment group differences at 30 days and at 1 year in stroke (p = 0.68 and p = 0.99, respectively), in myocardial infarction [MI] (p = 0.90 and p = 0.22, respectively), or in the need for the revascularization of the target vessel for ischaemia (p = 0.18 and p = 0.12, respectively). There were two decision-analytic models: the base-case scenario used 1-year follow-up data from the RCT; and a sensitivity analysis used 3-year follow-up data. Resource use was primarily drawn from this RCT. Health-related quality-of-life (HR-QOL) estimates were drawn from a UK cohort study. Both models evaluated the incremental costs and outcomes of bivalirudin compared with heparin plus GPI for patients with STEMI intended for PPCI. The analysis adopted a UK NHS perspective over a lifetime horizon. Unit costs were based on year 2009-2010 prices. The model adopted a decision-tree structure to reflect initial events for the initial period (stroke, repeat MI, minor/major bleeding events, repeat revascularizat

Topics: Adult; Antithrombins; Decision Support Techniques; Decision Trees; Drug Industry; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; United Kingdom

The direct thrombin inhibitor bivalirudin has gained popularity in cardiovascular medicine over the past decade because, in comparison with unfractionated heparin, it guarantees a predictable dose-related degree of anticoagulation with a low immunogenic profile and, possibly, with reduced rates of major bleeding complications. In the past bivalirudin has been frequently employed in the management of patients with heparin-induced thrombocytopenia. The REPLACE-2, ACUITY and ISAR-REACT4 studies demonstrated bivalirudin non-inferiority in comparison with unfractionated heparin in terms of ischemic end-points with a reduction of the bleeding rate also in patients acute coronary syndrome without ST elevation. Finally the results of the HORIZONS-AMI study positioned this drug as a first choice anticoagulant during percutaneous coronary interventions in patients with ST-elevation myocardial infarction. In fact the bivalirudin alone regimen, compared to unfractionated heparin plus GP2b3a inhibitors, decreased in-hospital bleeding rates and short and long term mortality. Given the body of clinical evidence, bivalirudin is likely to contend to GP2b3a inhibitors the leading place among the proposed anticoagulation strategies in the setting of acute coronary syndromes. The duration of the bivalirudin infusion after PCI and the optimal oral antiplatelet regimen associated to bivalirudin are important issues to be solved in future randomized controlled studies.

Topics: Antithrombins; Cardiovascular Diseases; Chemotherapy, Adjuvant; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; 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

Platelets play a pivotal role in the pathogenesis of coronary artery disease and myocardial infarction. Therefore, great interests have been focused in the last decades on improvement in antiplatelet therapies, that currently are regarded as main pillars in the prevention and treatment of coronary artery disease, with special attention to glycoprotein IIb-IIIa (GP IIb-IIIa) receptors, that mediates the final stage of platelet activation. GP IIb-IIIa inhibitors, especially abciximab, have been shown to improve clinical outcome in patients undergoing primary angioplasty for STEMI. Upstream administration cannot routinely recommended, but may potentially be considered among high-risk patients within the first 4 h from symptoms onset. In case of periprocedural administration of antithrombotic therapy, Bivalirudin should be considered, especially in patients at high risk for bleeding complications. Among high-risk patients with acute coronary syndromes, an early invasive strategy with selective downstream administration of GP IIb-IIIa inhibitors is the strategy of choice, whereas bivalirudin should be considered in patients at high risk for bleeding complications. Among patients with unstable angina GP IIb-IIIa inhibitors should be considered only in case of evidence of intracoronary thrombus or in case of thrombotic complications (as provisional use). Further, randomized trials are certainly needed in the era of new oral antiplatelet therapies, and with strategies to prevent bleeding complications such as larger use of radial approach, mechanical closure devices, bivalirudin, or postprocedural protamine administration to promote early sheat removal.

Topics: Acute Coronary Syndrome; Animals; Anticoagulants; Combined Modality Therapy; Coronary Artery Disease; Electrocardiography; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prognosis; Recombinant Proteins; Recurrence

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

The combination of unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPIs) has been a frequently used anti-thrombotic treatment strategy for acute coronary syndrome patients, including those with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. However, the ischemic benefit of the UFH plus GPI combination came at the expense of high rates of bleeding complications and thrombocytopenia, both of which have been independently associated with increased mortality. By contrast, bivalirudin monotherapy compared with the combination of UFH plus GPI resulted in improved net clinical outcomes, based on similar ischemic protection with significant reductions in bleeding complications in randomized trials including patients with stable angina, those with unstable angina and those with non-ST-segment elevation myocardial infarction. More recently, the HORIZONS-AMI randomized, open-label, multicenter trial has compared the efficacy and safety of bivalirudin alone versus UFH plus a GPI in 3602 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Clinical results derived from this large study, including the final 3-year follow-up data, will be reviewed in the present clinical trial report.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Combined Modality Therapy; Drug Therapy, Combination; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; 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

Bivalirudin is a synthetic 20 amino acid polypeptide that directly inhibits both fibrin-bound and soluble thrombin. In the randomized, open-label, multicentre HORIZONS-AMI trial in patients with ST-segment elevation myocardial infarction (STEMI) who were undergoing primary percutaneous coronary intervention (PCI), compared with unfractionated heparin (UFH) plus a glycoprotein (GP) IIb/IIIa inhibitor, bivalirudin was associated with a significantly lower 30-day rate of net adverse clinical events that was largely due to the significantly lower 30-day rate of non-coronary-artery bypass grafting major bleeding. There was no significant between-group difference in the 30-day rate of major adverse cardiovascular events. These 30-day clinical outcomes were maintained at the 1- and 2-year follow-up. Bivalirudin, compared with UFH plus a GP IIb/IIIa inhibitor, was associated with lower short- (30-day) and long- (1- and 2-year) term overall and cardiac mortality rates. Although there was an increased risk of acute stent thrombosis within 24 hours in recipients of bivalirudin compared with UFH plus a GP IIb/IIIa inhibitor, there was no significant between-group difference between 24 hours and 30 days,

Topics: Blood Coagulation; Clinical Trials as Topic; Electrocardiography; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombin; Treatment Outcome

Controversy regarding the optimal antiplatelet/antithrombotic regimen indicates a need to re-evaluate the place of these agents in treating patients with unstable angina/non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.. Although clinical trial data suggest that glycoprotein IIb-IIIa inhibition benefits moderate-risk to high-risk patients, recent studies question the use of intensive antiplatelet therapy in lower risk patients. The resultant shift towards less intensive alternative regimens raises questions about identifying patients in whom an alternative strategy is preferable. The concept of risk stratification for coronary intervention has evolved from lesion-based categorization to include clinical factors, for example, elevated levels of cardiac troponin.. Risk factors for periprocedural complications during percutaneous coronary intervention can be divided into anatomic (unprotected left main stenting, bifurcation lesions, and diffuse disease) and clinical (older age, diabetes, renal disease, left ventricular function, recent myocardial damage, and female sex) factors. These may interact additively or synergistically, increasing the likelihood of complications in patients who might otherwise have been considered at low risk. We need to reconsider, therefore, how we identify appropriate options and, hopefully, optimize clinical outcomes. This review evaluates risk factors for periprocedural complications in an effort to determine patients who may benefit most from intensive antiplatelet regimens.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Perioperative Care; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Factors

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

New data have re-established the importance of anticoagulation of patients with ST segment elevation myocardial infarction (STEMI), both as an adjuvant to reperfusion therapy or in patients ineligible for reperfusion. Recent randomized trials have found newer agents to be superior to conventional unfractionated heparin. This article summarizes current understanding of the underlying pathophysiology of STEMI and provides a comprehensive review of emerging trial data for low molecular weight heparins, anti-factor Xa agents and direct thrombin inhibitors in this setting.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Polysaccharides; Recombinant Proteins; Thrombin; Thrombolytic Therapy; Treatment Outcome

Previously, indirect thrombin inhibitors such as unfractionated heparin or low-molecular-weight heparin were used as a standard anticoagulation during percutaneous coronary intervention to prevent procedural thrombotic complications but at a risk of hemorrhagic complications. More recently, bivalirudin, a member of the direct thrombin inhibitor class, has been shown to have 1) predictable pharmacokinetics, 2) ability to inhibit free- and clot-bound thrombin, 3) no properties of platelet activation, 4) avoidance of heparin-induced thrombocytopenia, and 5) a significant reduction of bleeding without a reduction in thrombotic or ischemic endpoints compared to heparin and glycoprotein IIbIIIa inhibitors when used in patients presenting with acute coronary syndrome who are planned for an invasive treatment strategy.

Topics: Acute Coronary Syndrome; Anemia; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Blood Coagulation; Comorbidity; Coronary Thrombosis; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombocytopenia

Coronary artery disease is the leading cause of death in the UK with a high clinical, social and economic burden. The management of acute coronary syndromes is rapidly evolving and clinicians are constantly challenged with incorporating new clinical pathways and guidelines into their practices. It is important for clinicians to have a sound working knowledge of acute coronary syndromes, and be updated on the emerging evidence to guide therapy and improve outcomes in these patients.

Topics: Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Antithrombins; Clopidogrel; Fondaparinux; Heparin, Low-Molecular-Weight; Hirudins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Recombinant Proteins; Thrombolytic Therapy; Ticlopidine

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

Economic evaluation plays an important role during almost all stages of pharmaceutical design and use. This paper reviews the recent pharmacoeconomic literature on the use of anticoagulants for acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI). Both ACS and PCI are common reasons for hospitalization and contribute significantly to costs of care. ACS and PCI practice standards are still evolving. For ACS enoxaparin does appear to be more cost-effective around the globe than unfractionated heparin (UFH) when clopidrogel and glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors are not used. With the high prevalence of clopidrogel and GP IIb/IIIa use, the question may be moot. Since the cost of UFH therapy, including the cost of anticoagulant monitoring, is less expensive than enoxaparin therapy, UFH is probably the more cost-effective strategy. For PCI, as ischemic complications were reduced during the mid'90's, bleeding complications have become the most common problem and a major cost driver. Other complications that can drive costs include the occurrence of MI and revascularization procedures (repeat PCI or CABG). Results suggest that bivalirudin plus a provisional GP IIb/IIIa inhibitor is the most cost-effective strategy for patients undergoing elective PCI. There is no clear evidence regarding its use in urgent PCI. ACS and PCI practice standards are still evolving. It would be useful to embed economic studies within new clinical trials. Full economic analysis of groups at high risk for bleeding while undergoing PCI is needed.

Topics: Acute Coronary Syndrome; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Cost-Benefit Analysis; Drug Costs; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Stents

In addition to antiplatelet therapy with aspirin, anticoagulation therapy with unfractionated heparin decreases the risk of myocardial infarction and death in patients with acute coronary syndromes. However, unfractionated heparin has pharmacologic limitations that limit efficacy and safety. Enoxaparin, fondaparinux, and bivalirudin are new anticoagulant therapy options with either superior efficacy or better safety than unfractionated heparin. Compared with unfractionated heparin, enoxaparin and fondaparinux are easier to administer, do not require monitoring, and facilitate longer treatment duration. Bivalirudin offers advantages for patients undergoing early percutaneous revascularization. Careful attention to dosing and excellent vascular access site management after cardiac catheterization are required to decrease the risk of bleeding and blood transfusion, which have been associated with increased mortality risk.

Topics: Angina, Unstable; Anticoagulants; Electrocardiography; Enoxaparin; Fondaparinux; Heart Conduction System; Heparin, Low-Molecular-Weight; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Polysaccharides; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

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

Direct thrombin inhibitors have several potential advantages over indirect thrombin inhibitors such as heparin. Bivalirudin, a bivalent direct thrombin inhibitor, is most commonly used in clinical practice and has a proven role in contemporary interventional medicine with elective percutaneous coronary intervention (PCI) as well as in patients with non-ST-elevation acute coronary syndrome (NSTEACS). Results from well-controlled clinical trials have shown that bivalirudin is associated with an approximate 50% reduction in major bleeding while having similar effects on incidence of death and myocardial infarction (MI) compared with herapin or enoxaparin and glycoprotein IIb/IIIa inhibitors. Bivalirudin has been successfully used in off- and on-pump cardiac surgery. Argatroban is the most evaluated among the univalent direct thrombin inhibitors inhibiting only the catalytic site of thrombin. It has been associated with similar rates of major bleeding compared with heparin in patients with acute MI receiving either streptokinase or alteplase with no effects on clinical endpoints. In a meta-analysis of 11 randomised trials where direct thrombin inhibitors (hirudin, bivalirudin, argatroban, efegatan or inogatran) were compared with unfractionated heparin in >35,000 patients with ST-elevation MI (STEMI) or NSTEACS there was no mortality difference between treatment groups but the incidence of MI at 30 days was significantly reduced in patients treated with direct thrombin inhibitors compared with heparin (4.7% vs 5.3%; p < 0.004). The role of direct thrombin inhibitors in both primary angioplasty for STEMI and angioplasty after fibrinolytic therapy needs to be established. Overall, the efficacy and improved safety profile make bivalirudin an attractive first-line anticoagulant for elective PCI and in patients with NSTEACS undergoing an invasive strategy.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Fibrinolysis; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Renal Insufficiency; Thrombin; Thrombocytopenia

Accomplishing a successful percutaneous coronary intervention in a patient with a suspected or diagnosed heparin-induced thrombocytopenia (HIT) requires the selection of an appropriate alternative anticoagulant and a thorough assessment of bleeding and thrombotic risks. In this review, we suggest an evidence-based management algorithm that takes into account the clinical phase of HIT (acute, recent, and remote HIT) and the associated risk when patients present with acute coronary syndrome. The algorithm also integrates preventive measures directed at decreasing the bleeding risk associated with the antithrombotic and invasive therapies used for HIT and percutaneous coronary intervention.

Topics: Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Therapy, Combination; Fibrinolytic Agents; Fondaparinux; Heparin; Heparinoids; Heparitin Sulfate; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombocytopenia; Vitamin K

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

Gp IIb/IIIa receptor antagonists have been the subject of much work in patients presenting with acute coronary syndrome with no ST elevation (ACS ST-). The initial studies (PRISM, PRISM-PLUS, PURSUIT, PARAGON, CAPTURE, GUSTO IV-ACS) were performed at the end of the 1990s and universally showed a significant reduction in an endpoint combining death and myocardial infarction, especially in patients with an elevation of troponin and treated by angioplasty. However, these studies were performed at a time when clopidogrel was not being used regularly for this indication. Four randomised studies have recently re-evaluated the significance of Gp IIb/IIIa blockers prescribed either on admission to coronary intensive care (ELISA-2, PRACTICE) or in the coronary angiography suite during angioplasty (ADVANCE, ISAR-REACT 2) in patients presenting with ACS ST- pre-treated with clopidogrel in association with aspirin and heparin. The results of these studies suggest that Gp IIb/IIIa blockers initiated at the start of angioplasty significantly reduce an endpoint combining death, myocardial infarction and the need for emergency revascularisation. On the other hand, studies in which Gp IIb/IIIa blockers are initiated in coronary intensive care have been negative, but they have only been carried out on small numbers. The results of the ACUITY study comparing bivalirudin and Gp IIb/IIIa blockers in this context have recently been published. Bivalirudin seems to compare well with Gp IIb/IIIa blockers in terms of ischemia, but it significantly reduces the occurrence of hemorrhagic events.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Hirudins; Humans; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Premedication; Recombinant Proteins; Ticlopidine; Troponin T

As the pathophysiology of acute coronary syndromes (ACS) has been clarified in recent years, major advances have been made in the management of the disease. The magnitude of the thrombotic process triggered upon plaque disruption is modulated by different elements that determine plaque and blood thrombogenicity. Thrombin plays a pivotal role in ACS because of its extensive procoagulant and prothrombotic actions. Antithrombotic therapy and powerful antiplatelet therapies, in addition to early percutaneous coronary intervention (PCI), have become central in the management of ACS. A number of options for anticoagulation regimens are available. However, many agents currently used have significant limitations, recognition of which has led to the development, evaluation and clinical introduction of the class of thrombin-specific anticoagulant agents. This paper will discuss the clinical development of the direct thrombin inhibitor bivalirudin as the core anticoagulant in the contemporary PCI setting and the implications for its use in ACS.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Atrial Fibrillation; Azetidines; Benzylamines; Clinical Trials as Topic; Coronary Disease; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thromboembolism; Thrombosis; Venous Thrombosis

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials as Topic; Coronary Disease; Fibrinolytic Agents; Hemostatics; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Thrombin

We describe a 64-year-old male with severe hemophilia A (factor VIII-dependent), acute myocardial infarction (MI) and congestive heart failure (CHF) who underwent successful multi-vessel percutaneous coronary intervention (PCI). The patient was administered factor VIII transfusion to maintain activity levels between 60-80%. Anticoagulation during the PCI procedure was maintained with the direct thrombin inhibitor, bivalirudin. There were no procedural complications and the patient was discharged home the following day. These results suggest that bivalirudin may be used effectively in patients at very high risk of bleeding with enhanced procedural safety.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Blood Component Transfusion; Coronary Angiography; Factor VIII; Hemophilia A; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Radiography, Interventional; Recombinant Proteins

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

Acute coronary syndromes (ACS) refer to a spectrum of myocardial ischemic disorders characterized by atherothrombotic plaque disruption. The management of ACS presents a challenge to the cardiologist because treatment strategies continue to evolve. Thrombin plays a pivotal role in thrombus formation, converting fibrinogen to fibrin, activating platelets, and recruiting additional platelets into the platelet-rich thrombus. In addition to unfractionated heparin (UFH), newer antithrombotic agents are now available and have significantly changed contemporary clinical practice. Low-molecular-weight heparins (LMWHs) has been shown to be superior to UFH in several trials. Direct thrombin inhibitors (DTIs) have been shown to be effective in patients undergoing elective coronary interventions and are being evaluated in patients with ACS. We review two classes of antithrombotic drugs, the LMWHs and the DTIs and discuss their current roles in the management of patients with ACS.

Topics: Aged; Anticoagulants; Arginine; Blood Platelets; Clinical Trials as Topic; Enoxaparin; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Hirudins; Humans; Middle Aged; Models, Biological; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Risk; Sulfonamides; Thrombin

The central role of thrombin in the initiation and propagation of intravascular thrombus provides a strong rationale for direct thrombin inhibitors in acute coronary syndromes (ACS). Direct thrombin inhibitors are theoretically likely to be more effective than indirect thrombin inhibitors, such as unfractionated heparin or low-molecular-weight heparin, because the heparins block only circulating thrombin, whereas direct thrombin inhibitors block both circulating and clot-bound thrombin. Several initial phase 3 trials did not demonstrate a convincing benefit of direct thrombin inhibitors over unfractionated heparin. However, the Direct Thrombin Inhibitor Trialists' Collaboration meta-analysis confirms the superiority of direct thrombin inhibitors, particularly hirudin and bivalirudin, over unfractionated heparin for the prevention of death or myocardial infarction (MI) during treatment in patients with ACS, primarily due to a reduction in MI (odds ratio, 0.80; 95% confidence interval, 0.70 to 0.91) with little impact on death. The absolute risk reduction in the composite of death or MI at the end of treatment (0.8%) was similar at 30 days (0.7%), indicating no loss of benefit after cessation of therapy. Supportive evidence for the superiority of direct thrombin inhibitors over heparin derives from the recently reported Hirulog and Early Reperfusion or Occlusion (HERO)-2 randomized trial with ST-segment elevation ACS, which demonstrated a similar benefit of bivalirudin over heparin for the prevention of death or MI at 30 days (absolute risk reduction 1.0%), again primarily due to a reduction in MI during treatment (odds ratio, 0.70; 95% confidence interval, 0.56 to 0.87), with little impact on death. Further evaluation of hirudin and bivalirudin in the antithrombotic management of patients with ACS is warranted.

Topics: Acute Disease; Angina, Unstable; Antithrombins; Coronary Thrombosis; Fibrinolytic Agents; Forecasting; Heparin; Hirudins; Humans; Meta-Analysis as Topic; Myocardial Infarction; Outcome Assessment, Health Care; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombin

Unfractionated heparin has been the cornerstone of antithrombin therapy in the treatment of non-ST-segment elevation acute coronary syndromes for more than a decade. Several new anticoagulants have emerged in recent years and have been studied extensively in patients with unstable coronary syndromes and in the percutaneous coronary intervention setting.. Direct thrombin inhibitors comprise a family of agents with promising properties that offer several potential advantages over unfractionated heparin. Hirudin has been studied in patients with ST-elevation myocardial infarction, non-ST-elevation coronary syndromes, and coronary angioplasty. Bivalirudin has been studied in patients undergoing percutaneous coronary revascularization, with very promising efficacy and safety profile compared with unfractionated heparin.. The clinical trials of direct thrombin inhibitors in non-ST-elevation acute coronary syndromes and coronary angioplasty are reviewed.

Topics: Angioplasty, Balloon, Coronary; Arginine; Clinical Trials as Topic; Coronary Disease; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thrombolytic Therapy

To obtain more reliable and precise estimates of the effect of direct thrombin inhibitors in the management of acute coronary syndromes, including patients undergoing percutaneous coronary intervention, we undertook a meta-analysis based on individual patients' data from randomised trials comparing a direct thrombin inhibitor (hirudin, bivalirudin, argatroban, efegatran, or inogatran) with heparin.. We included trials that involved at least 200 patients. The primary efficacy outcome was death or myocardial infarction, and the primary safety outcome was major bleeding. Data from individual trials were combined by use of a modified Mantel-Haenszel method.. In 11 randomised trials, 35,970 patients were assigned up to 7 days' treatment with a direct thrombin inhibitor or heparin and followed up for at least 30 days. Compared with heparin, direct thrombin inhibitors were associated with a lower risk of death or myocardial infarction at the end of treatment (4.3% vs 5.1%; odds ratio 0.85 [95% CI 0.77-0.94]; p=0.001) and at 30 days (7.4% vs 8.2%; 0.91 [0.84-0.99]; p=0.02). This was due primarily to a reduction in myocardial infarctions (2.8% vs 3.5%; 0.80 [0.71-0.90]; p<0.001) with no apparent effect on deaths (1.9% vs 2.0%; 0.97 [0.83-1.13]; p=0.69). Subgroup analyses suggested a benefit of direct thrombin inhibitors on death or myocardial infarction in trials of both acute coronary syndromes and percutaneous coronary interventions. A reduction in death or myocardial infarction was seen with hirudin and bivalirudin but not with univalent agents. Compared with heparin, there was an increased risk of major bleeding with hirudin, but a reduction with bivalirudin. There was no excess in intracranial haemorrhage with direct thrombin inhibitors.. Direct thrombin inhibitors are superior to heparin for the prevention of death or myocardial infarction in patients with acute coronary syndromes. This information should prompt further clinical development of direct thrombin inhibitors for the management of arterial thrombosis.

Topics: Angina, Unstable; Antithrombins; Arginine; Glycine; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Oligopeptides; Peptide Fragments; Pipecolic Acids; Piperidines; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Survival Rate; Thrombin

Studies of the anticoagulant effects of hirudin, which is derived from the saliva of the leech Hirudo medicinalis, led to the development of compounds that can directly inhibit thrombin activity without the need for additional cofactors. One of these is the direct thrombin inhibitor bivalirudin, which has recently been approved by the US Food and Drug Administration for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty.. This is a review of the pharmacologic properties, efficacy, tolerability, and potential cost-effectiveness of bivalirudin in the treatment of ischemic coronary syndromes.. Articles were identified by searches of MEDLINE (1966-September 2001), International Pharmaceutical Abstracts (1970-September 2001), and the Iowa Drug Information Service (1966-September 2001) using the terms bivalirudin and Hirulog. The reference lists of retrieved articles were also reviewed for relevant articles.. Bivalirudin is a synthetic polypeptide that directly inhibits thrombin by binding simultaneously to its active catalytic site and its substrate recognition site. After intravenous administration, peak plasma concentrations occur in 2 minutes. In patients given a 1.0-mg/kg bolus followed by a 2.5-mg/kg per hour infusion, a median activated clotting time of 346 seconds is achieved with little interpatient or intrapatient variability. Clearance of bivalirudin occurs through a combination of renal elimination and proteolytic cleavage, and doses may need to be decreased in the presence of renal dysfunction. In patients undergoing percutaneous coronary interventions, bivalirudin has been associated with equivalent efficacy but lower bleeding rates (P < 0.001) than unfractionated heparin (UFH). Data from the Hirulog Early Reperfusion/Occlusion-2 study suggest no reduction in mortality with bivalirudin compared with heparin when either is added to aspirin and streptokinase in patients with acute myocardial infarction, despite a lower reinfarction rate (P < 0.001). Experience with bivalirudin in patients with unstable angina and heparin-induced thrombocytopenia (HIT), as well as in patients receiving glycoprotein IIb/IIIla inhibitors, is limited. The differences in bleeding rates between bivalirudin and heparin in published clinical trials probably reflect differences in levels of anticoagulation achieved in comparator groups.. Given its high cost, bivalirudin should be reserved for use as an alternative to UFH, primarily in patients with HIT, until clinical trials have more clearly demonstrated its benefits in terms of efficacy or safety.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombocytopenia; Thrombosis

Bivalirudin, a synthetic analogue of hirudin, is a specific and reversible inhibitor of thrombin which binds directly with both fluid-phase and clot-bound thrombin. In patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA), results from a large well designed study and its reanalysis (n = 4312) indicate that bivalirudin is more effective than heparin in the prevention of ischaemic complications for up to 90 days after the start of treatment. In addition, among patients undergoing PTCA for post myocardial infarction (MI) bivalirudin may be more effective than heparin in preventing ischaemic complications for up to 180 days after treatment was started. Data from dose-finding studies indicate bivalirudin has potential in the treatment of patients with unstable angina not undergoing percutaneous coronary intervention (PCI); however, well designed comparative studies are needed before firm conclusions can be made. Among patients with acute ST elevation MI, randomised trials have demonstrated bivalirudin to be significantly more effective than heparin in improving early patency in patients receiving thrombolytic therapy with streptokinase. Data from the Hirulog and Early Reperfusion/Occlusion (HERO)-1 trial (n = 412) indicate that bivalirudin recipients were significantly more likely to have Thrombin Inhibition in Myocardial Ischaemia (TIMI) grade 3 flow at 90 to 120 minutes than heparin recipients. In addition, data from the HERO-2 trial (n = 17 073) show bivalirudin was significantly more effective than heparin in reducing adjudicated 96-hour reinfarction and 30-day investigator-reported death/reinfarction than heparin. Bivalirudin was as effective as heparin in reducing 30-day mortality. Data from a meta-analysis of four randomised trials among patients undergoing PTCA or treatment for acute coronary syndromes indicate that, at after 30 to 50 days of follow-up, bivalirudin was significantly more effective than heparin in reducing the incidence of nonfatal MI and the combined endpoint of death or nonfatal MI. The most significant adverse events associated with bivalirudin are bleeding complications. In individual trials, bivalirudin was as well tolerated as heparin with, in general, a reduced incidence of bleeding complications. Additionally, bivalirudin provides a more consistent, predictable anticoagulant response. In 4312 patients with unstable angina undergoing PTCA the incidence of retroperitoneal bleeding, blood tr. Bivalirudin is an effective alternative to heparin in the prevention of ischaemic complications in patients with unstable angina undergoing PTCA. In addition, the drug has shown potential in the treatment of patients with unstable angina not undergoing PCI. For patients with MI, it is clear that bivalirudin can replace heparin in the management of MI where streptokinase is used as the thrombolytic agent. Further data are required on the efficacy of bivalirudin in patients undergoing thrombolysis with newer thrombolytics.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Dose-Response Relationship, Drug; Drug Evaluation; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins

To review the primary literature describing the pharmacology and clinical uses of bivalirudin.. A MEDLINE search (January 1966-May 2001) was conducted that used bivalirudin, hirulog, and direct thrombin inhibitor as key words. References from retrieved articles and unpublished information acquired from the manufacturer and the Internet were also used.. All acquired articles that discussed the pharmacology, pharmacokinetics, and clinical efficacy of bivalirudin were reviewed.. Articles were selected based on content regarding the pharmacology and clinical use of bivalirudin. Given the paucity of data pertaining to the clinical use of bivalirudin, most articles were used, including abstracts and communications with the manufacturer.. Bivalirudin is a direct thrombin inhibitor that inactivates both unbound and fibrin-bound thrombin. Bivalirudin rapidly induces anticoagulation and has a relatively short duration of action. Bivalirudin displays linear kinetics and is primarily eliminated renally. Bivalirudin was proven effective in preventing postprocedural ischemic complications in patients with unstable or postinfarction angina who received percutaneous transluminal coronary angioplasty (PTCA). Yet, further investigations that include less critically ill patients and use the current clinical practice of administering glycoprotein IIb/IIIa antagonists and/or inserting intracoronary stents are needed to fully evaluate its efficacy. Bivalirudin has also induced early patency in patients with myocardial infarction in combination with streptokinase, but its use with newer thrombolytics needs to be studied. Bivalirudin has been used in patients with immunologically mediated, heparin-induced thrombocytopenia (HIT) without complications. Bleeding is the major adverse effect and occurs more commonly in patients with renal dysfunction.. At present, bivalirudin is worthy of consideration in patients requiring PTCA who have HIT. Advocating the routine use of bivalirudin in patients experiencing an acute coronary syndrome or HIT is premature.

Topics: Amino Acid Sequence; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials as Topic; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Heparin is a commonly used anticoagulant in patients with coronary artery disease but its use does not always result in low rates of ischaemic and bleeding events, so the search for new anticoagulants continues. Thrombin plays a key role in both thrombosis and haemostasis and direct thrombin inhibitors modelled on the hirudin molecule found in the saliva of the medicinal leech, Hirudo medicinalis, have recently been developed. To date, the only direct thrombin inhibitor shown to reduce both the ischaemic and the bleeding complications associated with percutaneous coronary intervention (PCI) is bivalirudin, which is approved for this indication in the US and New Zealand. This agent is currently being studied in patients undergoing PCI with or without glycoprotein IIb/IIIa inhibitors and stenting. Bivalirudin has been shown to significantly reduce the risk of reinfarction in patients with acute myocardial infarction (MI) treated with streptokinase, but its use for this indication is not approved in the US. It may also prove to be beneficial in patients with acute MI treated with other fibrinolytic regimens or with primary or facilitated PCI. Bivalirudin is suitable for use as an alternative to heparin in the majority of patients undergoing PCI and in patients receiving streptokinase for acute MI.

Topics: Acute Disease; Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials as Topic; Coronary Artery Disease; Coronary Disease; Coronary Thrombosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Inhibiting thrombin as a key enzyme of the coagulation cascade is therapeutically useful in thromboembolic diseases. In coronary thrombosis, direct thrombin inhibitors promise to be useful for an efficacious therapy. Hirudin and recombinant or synthetic mimetics like hirulog, argatroban and melagatran have proven their efficacy in clinical studies.. Therapy with direct thrombin inhibitors such as hirudin and analogous substances reduces coronary events. Moreover, the agents are useful for therapy of thromboembolic diseases, especially in the case of heparin induced thrombocytopenia type II.

Topics: Acute Disease; Angina, Unstable; Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Antithrombins; Arginine; Azetidines; Benzylamines; Fibrinolytic Agents; Glycine; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Rabbits; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thromboembolism; Thrombosis; Time Factors

This review focuses on the use of bivalirudin as a replacement anticoagulant for heparin in patients undergoing percutaneous coronary intervention, or who are being treated for unstable angina pectoris, ST-elevation, or non-ST-elevation myocardial infarction. Potential advantages of bivalirudin include a lack of dependence on antithrombin III for anticoagulant activity, the ability to inactivate both fibrin-bound and soluble thrombin, a lack of aggregatory effects on platelets, a predictable anticoagulant response without monitoring, and a wider therapeutic window. Clinical trial results to date suggest that bivlirudin is at least as effective as heparin with superior safety due to lower bleeding rates.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials as Topic; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

The goals of therapy for unstable angina and non-Q-wave myocardial infarction (MI) are to maintain myocardial perfusion by inhibiting platelet aggregation and fibrin deposition at sites of plaque rupture, thereby preventing ongoing or new myocardial ischemia and cardiac death. Although aspirin and heparin sodium are cornerstones in the management of unstable angina and non-Q-wave MI, both have significant limitations that have prompted the development of new agents. The thienopyridines, ticlopidine hydrochloride and clopidogrel, appear to be at least as effective as aspirin in the management of unstable angina. Glycoprotein IIb/IIIa receptor antagonists are a new class of platelet inhibitors that are more potent than aspirin, because they target the final common pathway of platelet aggregation. Low-molecular-weight heparins provide a more stable pharmacodynamic response and are more convenient to use than unfractionated heparin. Direct thrombin inhibitors show promise for inhibiting thrombin-mediated platelet aggregation and fibrin deposition. We focus on the opportunities presented by these agents, detailing mechanisms of action, advantages over aspirin and heparin, and performance in recent clinical trials.

Topics: Angina, Unstable; Antithrombins; Clopidogrel; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Receptors, Thromboxane; Recombinant Proteins; Thromboxane-A Synthase; Ticlopidine

Prompt treatment with thrombolytic therapy in acute myocardial infarction has been proven to reduce infarct size and mortality. However, reperfusion fails to occur in 30-50% of patients, either due to impaired epicardial artery flow or microvascular occlusion, with these patients experiencing a higher morbidity and mortality. We review the diagnosis and management of failed thrombolysis in acute myocardial infarction.

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Aspirin; Clinical Trials as Topic; Electrocardiography; Fibrinolytic Agents; Hirudin Therapy; Hirudins; Humans; Immunoglobulin Fab Fragments; Monitoring, Physiologic; Myocardial Infarction; Peptide Fragments; Plasminogen Activators; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Streptokinase; Thrombolytic Therapy; Time Factors

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Controlled Clinical Trials as Topic; Coronary Thrombosis; Dose-Response Relationship, Drug; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombolytic Therapy

The goal of anticoagulant therapy in unstable angina is to prevent progression of a subocclusive coronary thrombus to complete occlusion of the coronary artery, thereby preventing myocardial infarction and death. Although these have been many advances in therapy with anticoagulants, considerable morbidity and mortality remains. Also, although combination therapy with potent novel anticoagulants and antiplatelet agents may be an alternative strategy, this needs to be balanced against the risks of hemorrhagic complications. More precise and biologically relevant methods of monitoring anticoagulant effect, along with appropriately modified doses given in combination offers promise.

Topics: Angina, Unstable; Anticoagulants; Antithrombins; Arginine; Clinical Trials as Topic; Coronary Thrombosis; Disease Progression; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Warfarin

Thrombolytic therapy aims to achieve rapid and sustained infarct-related artery patency, although this results in a procoagulant state. Heparin has limitations as an antithrombin agent, which has led to clinical investigation of alternative agents. Direct thrombin inhibitors, as adjuncts to thrombolytic therapy, have been shown to increase 90 minute Thrombolysis in Myocardial Infarction (TIMI)-3 flow rates and reduce reinfarction, when compared with heparin. These results have been achieved with an acceptable risk of bleeding, when administered in appropriate dosing regimens. When the direct thrombin inhibitor hirudin was administered at a mean of 34 and 50 minutes after thrombolytic therapy in large clinical trials, there was no reduction in mortality. In contrast, in several angiographic studies, direct thrombin inhibitors were administered prior to thrombolysis. The effect on mortality of the administration of hirulog prior to streptokinase is currently being examined.

Topics: Antithrombins; Drug Therapy, Combination; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Streptokinase; Survival Analysis; Thrombin; Thrombolytic Therapy

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

Since the introduction of thrombolytic therapy for acute myocardial infarction, the incidence of coronary artery reocclusion has been intensively studied. Also, the prediction and diagnosis of reocclusion by angiographic and clinical variables, as well its invasive and pharmacologic prevention, have gained much attention. By angiographic definition, reocclusion requires three angiographic observations: one with an occluded artery, one with a reperfused artery and a third for the assessment of subsequent occlusion (true reocclusion). Since the introduction of early intravenous reperfusion therapy, most studies use only two angiograms: one with a patent and one with a nonpatent infarct-related artery. A search for all published reocclusion studies revealed 61 studies (6,061 patients) with at least two angiograms. The median time interval between the first angiogram after thrombolysis and the second was 16 days (range 0.1 to 365). Reocclusion was observed in 666 (11%) of 6,061 cases. Interestingly, the 28 true reocclusion studies showed an incidence of reocclusion of 16 +/- 10% (mean +/- SD), and the 33 studies with only two angiograms 10 +/- 8% (p=0.04), suggesting that proven initial occlusion of the infarct-related artery is a risk factor for reocclusion after successful thrombolysis. The other predictors for reocclusion are probably severity of residual stenosis of the infarct-related artery after thrombolysis and perhaps the flow state after lysis. Reocclusion is most frequently seen in the early weeks after thrombolysis. The clinical course in patients with reocclusion is more complicated than in those without this complication. Left ventricular contractile recovery after thrombolysis is hampered by reocclusion. Routine invasive strategies have not been proven effective against reocclusion. In the prevention of reocclusion, both antiplatelet and antithrombin strategies have been tested, including hirudin and hirulog, but the safety of these agents in thrombolysis is still questionable. Thus, reocclusion after thrombolysis is an early phenomenon and is more frequent after proven initial occlusion of the infarct-related artery. Reocclusion can be predicted by angiography after thrombolysis. Because reocclusion is detrimental, strategies to prevent it should be developed and carried out after thrombolytic therapy for acute myocardial infarction as soon as they are deemed safe.

Topics: Antithrombins; Constriction, Pathologic; Coronary Angiography; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Incidence; Myocardial Infarction; Peptide Fragments; Prognosis; Recombinant Proteins; Recurrence; Thrombolytic Therapy

Topics: Anticoagulants; Antithrombins; Arginine; Blood Platelets; Clinical Trials as Topic; Epoprostenol; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Oligopeptides; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Thrombolytic Therapy

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

Recombinant hirudin and hirudin analogues constitute interesting new antithrombotic agents that have distinct advantages over heparin. These agents specifically inhibit thrombin and all of its actions and also suppress further thrombin generation. As opposed to unfractionated heparin, hirudin and hirulog effectively suppress clot-bound thrombin, making these agents of particular interest in the treatment of arterial thrombosis, for example, following thrombolysis or percutaneous transthoracic angioplasty. The recent data derived from clinical trials supporting the use of hirudin and hirulog in the prevention and treatment of thrombotic diseases are reviewed here.

Topics: Angina, Unstable; Anticoagulants; Cardiovascular Diseases; Clinical Trials as Topic; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombolytic Therapy

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

Previous randomised trials of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) have reported conflicting results, in part because of treatment with different pharmacological regimens. We designed a large-scale trial examining bivalirudin with a post-PCI high-dose infusion compared with heparin alone, the regimens that previous studies have shown to have the best balance of safety and efficacy.. BRIGHT-4 was an investigator-initiated, open-label, randomised controlled trial conducted at 87 clinical centres in 63 cities in China. Patients with STEMI undergoing primary PCI with radial artery access within 48 h of symptom onset who had not received previous fibrinolytic therapy, anticoagulants, or glycoprotein IIb/IIIa inhibitors were randomly assigned (1:1) to receive bivalirudin with a post-PCI high-dose infusion for 2-4 h or unfractionated heparin monotherapy. There was no masking. Glycoprotein IIb/IIIa inhibitor use was reserved for procedural thrombotic complications in both groups. The primary endpoint was a composite of all-cause mortality or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. This trial is registered with ClinicalTrials.gov (NCT03822975), and is ongoing.. Between Feb 14, 2019, and April 7, 2022, a total of 6016 patients with STEMI undergoing primary PCI were randomly assigned to receive either bivalirudin plus a high-dose infusion after PCI (n=3009) or unfractionated heparin monotherapy (n=3007). Radial artery access was used in 5593 (93·1%) of 6008 patients. Compared with heparin monotherapy, bivalirudin reduced the 30-day rate of the primary endpoint (132 events [4·39%] in the heparin group vs 92 events [3·06%] in the bivalirudin group; difference, 1·33%, 95% CI 0·38-2·29%; hazard ratio [HR] 0·69, 95% CI 0·53-0·91; p=0·0070). All-cause mortality within 30 days occurred in 118 (3·92%) heparin-assigned patients and in 89 (2·96%) bivalirudin-assigned patients (HR 0·75; 95% CI 0·57-0·99; p=0·0420), and BARC types 3-5 bleeding occurred in 24 (0·80%) heparin-assigned patients and five (0·17%) bivalirudin-assigned patients (HR 0·21; 95% CI 0·08-0·54; p=0·0014). There were no significant differences in the 30-day rates of reinfarction, stroke, or ischaemia-driven target vessel revascularisation between the groups. Within 30 days, stent thrombosis occurred in 11 (0·37%) of bivalirudin-assigned patients and 33 (1·10%) of heparin-assigned patients (p=0·0015).. In patients with STEMI undergoing primary PCI predominantly with radial artery access, anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2-4 h significantly reduced the 30-day composite rate of all-cause mortality or BARC types 3-5 major bleeding compared with heparin monotherapy.. Chinese Society of Cardiology Foundation (CSCF2019A01), and a research grant from Jiangsu Hengrui Pharmaceuticals.

Topics: Drug Therapy, Combination; Hemorrhage; Heparin; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; ST Elevation Myocardial Infarction; Thrombosis

Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y. In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days.

Topics: Aged; Anticoagulants; Antithrombins; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; ST Elevation Myocardial Infarction; 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

Recent randomized controlled trials comparing femoral and radial access in primary percutaneous coronary intervention (PPCI) have shown conflicting results regarding the incidence of major adverse cardiovascular events (MACE) and major bleeding.. Using data from the HEAT-PPCI trial, we compared the primary efficacy (all-cause mortality, stroke, new myocardial infarction or unplanned repeat revascularization) and safety (major bleeding BARC 3-5) outcomes at 28 days, by final access site used (radial or femoral) and by default operator type. We then assessed outcomes in femoral cases performed by both operator types.. Radial access (RA) was associated with fewer MACE (91/1472 = 6.2% vs. 36/332 = 10.8% P = .003) and major bleeding events (38/1472 = 2.6% vs 22/332 = 6.6% P = .001) when compared to femoral access (FA). When analyzing outcomes by default operator type, there was a similar incidence of MACE (111/1575 = 7% vs 16/229 = 7% P = .97) and major bleeding events (49/1575 = 3.1% vs 11/229 = 4.8% P = .18). In cases where FA was performed by default radial operators, there was a higher rate of MACE (22/122 = 18% vs 14/210 = 6.7% P = .003) and major bleeding events (11/122 = 9% vs 11/210 = 5.2% P < .001), potentially explained by a higher risk profile in these cases.. Default femoral operators achieved comparable outcomes when compared to default radial operators. The less favorable outcomes observed in FA cases may result from its selective use by radial operators in high risk cases.

Topics: Aged; Anticoagulants; Antithrombins; Cause of Death; Femoral Artery; Heparin; Hirudins; Humans; Incidence; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Postoperative Hemorrhage; Pressure; Radial Artery; Recombinant Proteins; Recurrence; Reoperation; ST Elevation Myocardial Infarction; Stroke; Surgeons; Treatment Outcome; Vascular Closure Devices

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

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 aim of the study was to investigate whether bivalirudin versus unfractionated heparin (UFH) reduces infarct size (IS) for primary percutaneous coronary intervention (PPCI) in large acute myocardial infarction (AMI).. This multicentre open-label trial randomised 78 patients undergoing PPCI for large AMI to bivalirudin or UFH. The primary endpoint was IS, assessed by cardiac magnetic resonance (CMR) five days after PPCI. Secondary endpoints included index of microcirculatory resistance (IMR), CMR-assessed microvascular obstruction (MVO) and ejection fraction, and biomarkers for thrombin activity and cell injury. No difference was observed in mean IS at five days (25.0±19.7 g for bivalirudin vs. 27.1±20.7 g for UFH; p=0.75). Early MVO was numerically lower with bivalirudin (5.3±5.8 g vs. 7.7±6.3 g; p=0.17), with no significant difference in ejection fraction at 90 days (54.6±12.0% vs. 49.1±12.1%; p=0.11). In the biomarkers, thrombin-antithrombin complexes were reduced by 4.8 ug/L over the first day for bivalirudin versus an increase of 1.9 ug/L in the heparin arm (p=0.0003). Acute IMR was lower (43.5±21.6 vs. 68.7±35.8 mmHg×s, respectively; p=0.014). In a planned interim analysis, an approximate 11% reduction in IS was observed with bivalirudin; the trial was discontinued for futility.. This study did not achieve its primary endpoint of significant infarct size reduction in PPCI by prolonged bivalirudin infusion compared to UFH, even though complete thrombin inhibition was achieved in the acute phase, with a lower myocardial microcirculation resistance at the end of the procedure.

Topics: Aged; Anticoagulants; Antithrombins; Female; Heart Ventricles; Heparin; Hirudins; Humans; Infarction; Male; Microcirculation; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; 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 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

In this prespecified BRAVE 4 substudy we examined the antiplatelet and anticoagulant efficacy of clopidogrel plus heparin vs. prasugrel plus bivalirudin in patients with ST-segment elevation myocardial infarction.. 26 patients received clopidogrel/heparin, 25 patients received prasugrel/bivalirudin and 20 additional untreated patients served as controls. Platelet aggregation was tested using whole blood impedance aggregometry. Dynamic platelet adhesion and aggregate formation to collagen were quantified under flow conditions. Coagulation tests included activated partial thromboplastin time (aPTT), international normalized ratio (INR) as well as rotational thrombelastography (ROTEM®). Analyses were performed 3 and 72h after drug administration.. At 3, but not at 72h we observed a significant increase in the inhibition of platelet aggregation in response to adenosine diphosphate (P<0.01), but not to arachidonic acid, collagen or thrombin receptor agonist in the prasugrel/bivalirudin group compared to the clopidogrel/heparin group. Inhibition of platelet adhesion to collagen under flow was significantly stronger in the prasugrel/bivalirudin group at 3 and 72h after drug administration (P<0.01). APTT was significantly higher in the clopidogrel/heparin group (P<0.05) and INR was significantly higher in the prasugrel/bivalirudin group (P<0.01) 3h after drug administration. Concerning ROTEM® analysis the drug combinations did not differ in reducing clot formation time (CFT) and both combinations did not influence maximum clot firmness (MCF) compared to the controls.. We could demonstrate a more pronounced inhibition of platelet aggregation as well as platelet adhesion and aggregate formation to collagen under flow in prasugrel plus bivalirudin treated patients.

Topics: Antithrombins; Clopidogrel; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Recombinant Proteins; Reproducibility of Results; Sensitivity and Specificity; Thrombelastography; Ticlopidine; Treatment Outcome

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

Early stent thrombosis (ST) within 30 days after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction is a serious event. We sought to determine the predictors of and risk of mortality after early ST according to procedural antithrombotic therapy.. In a patient-level pooled analysis from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) trials, we examined 30-day outcomes in 4935 patients undergoing primary percutaneous coronary intervention with stent implantation at 188 international sites, randomized to either bivalirudin or heparin±a glycoprotein IIb/IIIa inhibitor (GPI). Early ST occurred in 100 patients (2.0%), 20 of whom (20.0%) died. Bivalirudin was associated with higher rates of early ST compared with heparin±GPI (2.5% versus 1.6%, P=0.04), because of more acute (≤24 h) ST (1.5% versus 0.2%, P<0.0001), with the risk limited to the first 4 hours after percutaneous coronary intervention. The rates of subacute (1-30 days) ST were similar with bivalirudin and heparin±GPI (1.0% versus 1.4%, P=0.24). Among patients with early ST, mortality within 30 days occurred in 4 of 60 (6.7%) bivalirudin-treated patients compared with 16 of 40 (40.0%) heparin±GPI-treated patients (adjusted hazard ratio, 0.12; 95% CI, 0.04-0.39; P=0.0004 and adjusted hazard ratio, 0.122; 95% CI, 0.04-0.39; P=0. 0004). Thus, 30-day mortality attributable to early ST occurred in 4 of 2479 (0.2%) bivalirudin-treated patients versus 16 of 2456 (0.7%) heparin±GPI-treated patients (P=0.007).. In the present large-scale pooled analysis from 2 multicenter randomized trials, early ST was more frequent in patients treated with bivalirudin compared with heparin±GPI because of increased ST within 4 hours after primary percutaneous coronary intervention. However, the mortality attributable to early ST was significantly lower after bivalirudin than after heparin±GPI.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00433966 (HORIZONS-AMI) and NCT01087723 (EUROMAX).

Topics: Aged; Blood Vessel Prosthesis Implantation; Electrocardiography; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Patient Outcome Assessment; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Stents; Survival Analysis; Thrombosis

Optimal antithrombotic pharmacotherapy in patients affected by diabetes mellitus (DM) undergoing percutaneous coronary intervention is unclear. We sought to evaluate the safety and efficacy of bivalirudin compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with DM undergoing percutaneous coronary intervention. We pooled patient-level data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events-2, Acute Catheterization and Urgent Intervention Triage strategy, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trials. The primary efficacy end point was the incidence of major adverse cardiac events, defined as the composite of death, myocardial infarction, or unplanned revascularization at 30 days. The primary safety end point was the incidence of 30-day non-coronary artery bypass graft-related major bleeding. All-cause mortality was reported at 30 days and 1 year. Of the 14,737 patients included in the pooled database, 3,641 (24.7%) had DM. Patients with DM had higher rates of 30-day major bleeding and 30-day and 1-year all-cause mortality. There were no differences in 30-day major adverse cardiac events between bivalirudin versus heparin plus GPI in patients with DM (6.9% vs 7.8%; relative risk [RR] 0.89, 95% CI 0.71 to 1.12) or without DM (7.5% vs 6.7%; RR 1.11, 95% CI 0.97 to 1.27; pinteraction = 0.10). Bivalirudin treatment was associated with reduced risk of major bleeding in similar magnitude in patients with DM (4.3% vs 6.6% RR 0.68, 95% CI 0.51 to 0.89) or without DM (3.2% vs 6.1%; RR 0.51, 95% CI 0.43 to 0.61; pinteraction = 0.15). The hemorrhagic benefit of bivalirudin was noted for both access site- and non-access site-related bleeding. Overall, bivalirudin treatment was associated with a significant 1-year mortality benefit (2.7% vs 3.3%; RR 0.82, 95% CI 0.68 to 0.98; p = 0.03), which was consistent between patients with or without DM (pinteraction = 0.30). In conclusion, compared with heparin plus GPI, bivalirudin was associated with similar 30-day antithrombotic efficacy and better 30-day freedom from bleeding and 1-year mortality, irrespective of diabetic status.

Topics: Aged; Antithrombins; Case-Control Studies; Diabetes Complications; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

In the HORIZONS-AMI trial, bivalirudin compared to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) improved net clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) at the cost of an increased rate of acute stent thrombosis. We sought to examine whether these effects are dependent on time to treatment.. The interaction between anticoagulation regimen and symptom onset to first balloon inflation time (SBT) on the 30-day and three-year rates of major adverse cardiac events (MACE) was examined in 3,199 randomised patients according to SBT ≤3 hours versus >3 hours. Among patients with an SBT ≤3 hours, bivalirudin resulted in higher 30-day rates of MACE compared to UFH plus a GPI. Non-significant differences were observed in patients with an SBT >3 hours. Similar results were found for MACE at three years and stent thrombosis and reinfarction at 30 days and three years. By multivariable analysis, bivalirudin was an independent predictor of MACE at 30 days and three years in patients with an SBT ≤3 hours, but not in patients with SBT >3 hours.. Bivalirudin compared to UFH plus a GPI is associated with an increased rate of stent thrombosis and MACE in patients with short SBTs, but not in those with longer SBTs.

Topics: Aged; Anticoagulants; Antithrombins; Cause of Death; Drug Therapy, Combination; Female; Graft Occlusion, Vascular; Heparin; Hirudins; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Recurrence; ST Elevation Myocardial Infarction; Stroke; Thrombosis; Time-to-Treatment; Treatment Outcome

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

This study sought to determine clinical, procedural, and treatment factors associated with acute stent thrombosis (AST) in the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial.. Bivalirudin started during transport for primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction significantly reduced major bleeding compared with heparin with or without glycoprotein IIb/IIIa inhibitors (GPI), but it was associated with an increase in AST.. We compared patients with (n = 12) or without AST (n = 2,184) regarding baseline, clinical, and procedural characteristics and antithrombotic treatment strategies (choice of P2Y12 inhibitor, post-primary PCI bivalirudin infusion dose [0.25 mg/kg/h, or BIV-LOW] vs. [1.75 mg/kg/h, or BIV-PCI] vs. heparin ± GPI). Logistic regression was performed to identify independent correlates of AST.. The overall AST rate was 0.6% and was higher with bivalirudin than with heparin ± GPI (1.1% vs. 0.2%; p = 0.007). Median time to AST was 2.3 h (interquartile range: 1.9 to 2.8 h). Patients with AST had less hypertension (2 of 14 [14.0%] vs. 961 of 2,182 [44.0%]; p = 0.03), and more frequently received GPI (11 of 14 [78.6%] vs. 880 of 2,183 [40.3%]; p = 0.004). Multivariate analysis using Firth penalized maximum likelihood estimation found hypertension (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.07 to 0.92; p = 0.037) and BIV-LOW (OR: 5.8, 95% CI: 1.5 to 22.2; p = 0.010) predictive of AST. Choice of P2Y12 inhibitor had no impact on AST. Compared with heparin ± GPI, AST rates were higher for BIV-LOW (11 of 670 [1.6%] vs. 2 of 947 [0.2%]; p = 0.008), but not different for BIV-PCI (1 of 244 [0.4%]; p = 0.588).. In this post-hoc analysis from EUROMAX, AST occurred very early and was not mitigated by the novel P2Y12 inhibitors. Prolonging the bivalirudin infusion at the PCI dose (but not at a lower dose) appeared to mitigate the risk of AST.

Topics: Aged; Ambulances; Anticoagulants; Chi-Square Distribution; Coronary Angiography; Coronary Thrombosis; Drug Administration Schedule; Europe; Female; Heparin; Hirudins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Recombinant Proteins; Risk Factors; Stents; Time Factors; 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

Residual thrombus accumulation around stent struts has been observed after the end of primary PCI and may represent a risk factor for acute stent thrombosis. The aim of this study is to test whether a strategy of prolonged bivalirudin infusion may reduce thrombosis of stent struts as compared to an intraprocedural only administration in subjects undergoing primary PCI.. One hundred and sixty patients will be selected from the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) study with all the following inclusion criteria: a) STEMI patients undergoing primary PCI with stent implantation, b) randomisation to standard or prolonged bivalirudin treatment arm, and c) at least one critical (>70%) stenosis of non-infarct-related coronary vessels suitable for staged PCI. Optical coherence tomography (OCT) of the infarct-related artery will be performed at the end of primary PCI and at the time of staged PCI which will be performed three to five days after the index procedure. The percentage difference in minimal flow area and in the number of stent cross-sections with a thrombotic area >5% will be measured at the end of primary PCI and at the time of staged PCI.. The MATRIX OCT substudy will establish whether prolonging the infusion of bivalirudin after the end of primary PCI may reduce the amount of residual thrombotic material on stent struts. The effect of the long-infusion strategy on clinical outcome will be elucidated by the MATRIX study.

Topics: Acute Coronary Syndrome; Antithrombins; Coronary Thrombosis; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Stents; Time Factors; Tomography, Optical Coherence; 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

Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome.. We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events.. The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34).. In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Combined Modality Therapy; Coronary Thrombosis; Female; Heparin; Hirudins; Humans; Incidence; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Stents; Stroke

Left ventricular (LV) dysfunction during and after hospitalization for ST-segment elevation myocardial infarction (STEMI) is associated with increased mortality. Whether baseline LV dysfunction impacts STEMI outcomes is not well studied. Furthermore, whether bivalirudin and paclitaxel-eluting stents (PES) are beneficial in patients with LV dysfunction is unknown. We studied the impact of left ventricular ejection fraction (LVEF) on outcomes of patients with STEMI in the HORIZONS-AMI trial.. LVEF was determined in 2648 (73.5%) of 3602 enrolled STEMI patients, who were divided into three groups according to LV function: (1) severely impaired (LVEF <40%); (2) moderately impaired (LVEF 40-50%); and (3) normal (LVEF ≥50%).. Compared to patients with normal LV function, those with severely impaired LVEF had higher 1-year rates of net adverse clinical events (27.1 vs. 14.2%, p<0.0001), major adverse cardiovascular events (20.7 vs. 9.5%, p<0.0001), cardiac death (10.6 vs. 1.2%, p<0.0001), and non-coronary artery bypass graft major bleeding (12.5 vs. 6.6%, p=0.001), differences which persisted after adjustment for baseline characteristics. Among patients with LVEF <40%, treatment with bivalirudin compared to heparin+GPIIb/IIIa inhibitors resulted in reduced 1-year mortality (5.8 vs. 18.3%, p=0.007). Patients with LVEF <40% receiving PES rather than bare metal stents had lower rates of 1-year ischaemia-driven target lesion revascularization (2.9 vs. 12.6%, p=0.02) and reinfarction (4.5 vs. 14.7%, p=0.03).. Among patients with STEMI undergoing primary percutaneous coronary intervention, adverse events are markedly increased in those with LVEF <40% during the index revascularization procedure. Nevertheless, these high-risk patients experience substantial clinical benefits from bivalirudin and PES.

Topics: Aged; Antithrombins; Coronary Angiography; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Gated Blood-Pool Imaging; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; Recombinant Proteins; Treatment Outcome; Ventricular Function, Left

Prasugrel is more potent than clopidogrel, but it is not known whether this translates into clinical benefit in patients undergoing primary percutaneous coronary intervention (PCI) with bivalirudin for ST elevation myocardial infarction. In the Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction trial, 452 patients with anterior STEMI undergoing primary PCI with bivalirudin were randomized to intralesional abciximab or placebo and to thrombus aspiration or no aspiration. Clopidogrel or prasugrel were administered at physician discretion. The primary end point was infarct size at 30 days by cardiac magnetic resonance imaging. Clinical events at 30 days and 1 year were independently adjudicated. Propensity score was used to adjust for nonrandom allocation of the drugs. Prasugrel and clopidogrel were administered to 155 patients (34.3%) and 297 patients (65.7%), respectively. Patients receiving prasugrel were younger with higher left ventricular ejection fraction and greater use of drug-eluting stents. Prasugrel-treated patients had higher rates of procedural success (94% vs 89%, p = 0.03), Thrombolysis In Myocardial Infarction (TIMI) 3 flow (95% vs 90%, p = 0.06), and lower corrected TIMI frame counts (21 ± 6 vs 23 ± 11, p = 0.008). At 30 days, infarct size was marginally lower in the prasugrel group (median [interquartile range] = 16.4% [6.5 to 20.0] vs 17.6% [8.1 to 25.7], p = 0.06). At 1 year, prasugrel group had significantly fewer deaths (1.3% vs 8.3%, p = 0.004) and fewer episodes of severe heart failure (2.0% vs 7.7%, p = 0.02). These findings persisted after propensity score adjustment. There were no significant differences in major bleeding. Stent thrombosis was 0% versus 2.5%, respectively, p = 0.054. We conclude that prasugrel was associated with improved efficacy and similar safety compared with clopidogrel in patients undergoing primary PCI with bivalirudin.

Topics: Antithrombins; Clopidogrel; Coronary Angiography; Electrocardiography; Female; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Thiophenes; Ticlopidine; Treatment Outcome

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI). Effective and safe adjunct antithrombotic therapy is a major determinant for short- and long-term outcomes after primary PCI. Two separate studies have shown significant benefits vs conventional therapy for 2 recently approved drugs. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors. However, during the first 24 hours after PCI, there was an increase in stent thrombosis rates with bivalirudin. In the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 trial, prasugrel was superior to clopidogrel in patients with acute coronary syndrome with and without ST-segment elevation. The synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing primary PCI. However, no specifically designed studies have so far compared the combination of prasugrel plus bivalirudin with that of clopidogrel plus unfractionated heparin in these patients. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is a randomized, open-label, multicenter trial aimed to test the hypothesis that a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus unfractionated heparin in terms of net clinical outcome in STEMI patients with planned primary PCI.

Topics: Anticoagulants; Clopidogrel; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Thiophenes; Ticlopidine; Treatment Outcome

Whether prasugrel plus bivalirudin is a superior strategy to unfractionated heparin plus clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has never been assessed in specifically designed randomized trials.. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is an investigator-initiated, randomized, open-label, multicentre trial, designed to test the hypothesis that in STEMI patients with planned primary PCI a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus heparin in terms of net clinical outcome. Owing to slow recruitment, the trial was stopped prematurely after enrolment of 548 of 1240 planned patients. At 30 days, the primary composite endpoint of death, myocardial infarction, unplanned revascularization of the infarct related artery, stent thrombosis, stroke, or bleeding was observed in 42 patients (15.6%) randomized to prasugrel plus bivalirudin and 40 patients (14.5%) randomized to clopidogrel plus heparin [relative risk, 1.09; one-sided 97.5% confidence interval (CI) 0-1.79, P = 0.680]. The composite ischaemic endpoint of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, or stroke occurred in 13 patients (4.8%) in the prasugrel plus bivalirudin group and 15 patients (5.5%) in the clopidogrel plus heparin group (relative risk, 0.89; 95% CI 0.40-1.96, P = 0.894). Bleeding according to the HORIZONS-AMI definition was observed in 38 patients (14.1%) in the prasugrel plus bivalirudin group and 33 patients (12.0%) in the clopidogrel plus heparin group (relative risk, 1.18; 95% CI 0.74-1.88, P = 0.543). Results were consistent across various subgroups of patients.. In this randomized trial of STEMI patients, we were unable to demonstrate significant differences in net clinical outcome between prasugrel plus bivalirudin and clopidogrel plus heparin. Neither the composite of ischaemic complications nor bleeding were favourably affected by prasugrel plus bivalirudin compared with a regimen of clopidogrel plus unfractionated heparin. However, the results must be interpreted in view of the premature termination of the trial.. Unique identifier NCT00976092 (www.clinicaltrials.gov).

Topics: Aged; Anticoagulants; Clopidogrel; Coronary Angiography; Coronary Stenosis; Drug Therapy, Combination; Early Termination of Clinical Trials; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticlopidine; Treatment Outcome

In the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention (PCI) compared with heparin and routine glycoprotein IIb/IIIa inhibitors (GPI). It is unknown whether this advantage of bivalirudin is observed in comparison with heparins only with GPI used as bailout.. In the EUROMAX study, 2198 patients with ST-segment elevation myocardial infarction (STEMI) were randomized during transport for primary PCI to bivalirudin or to heparins with optional GPI. Primary and principal outcome was the composites of death or non-CABG-related major bleeding at 30 days. This pre-specified analysis compared patients receiving bivalirudin (n = 1089) with those receiving heparins with routine upstream GPI (n = 649) and those receiving heparins only with GPI use restricted to bailout (n = 460). The primary outcome death and major bleeding occurred in 5.1% with bivalirudin, 7.6% with heparin plus routine GPI (HR 0.67 and 95% CI 0.46-0.97, P = 0.034), and 9.8% with heparins plus bailout GPI (HR 0.52 and 95% CI 0.35-0.75, P = 0.006). Following adjustment by logistic regression, bivalirudin was still associated with significantly lower rates of the primary outcome (odds ratio 0.53, 95% CI 0.33-0.87) and major bleeding (odds ratio 0.44, 95% CI 0.24-0.82) compared with heparins alone with bailout GPI. Rates of stent thrombosis were higher with bivalirudin (1.6 vs. 0.6 vs. 0.4%, P = 0.09 and 0.09).. Bivalirudin, started during transport for primary PCI, reduces major bleeding compared with both patients treated with heparin only plus bailout GPI and patients treated with heparin and routine GPI, but increased stent thrombosis.

Topics: Aged; Anticoagulants; Antithrombins; Drug Therapy, Combination; Emergency Treatment; Female; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Transportation of Patients

Reinfarction after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction has negative consequences. Little is known about reinfarction after drug-eluting stents and bivalirudin anticoagulation. We, therefore, sought to determine the incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in the contemporary era.. Outcomes were assessed in 3202 patients undergoing stent implantation for ST-segment-elevation myocardial infarction in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Independent predictors of reinfarction and mortality were identified by Cox proportional hazards modeling. The cumulative incidence of reinfarction was 1.8% at 30 days, 4.0% at 1 year, and 6.9% at 3 years. Definite stent thrombosis was responsible for 76.3% of reinfarctions occurring within 30 days and 52.0% of all reinfarctions within 3 years. Independent predictors of reinfarction were current smoking, Killip class ≥2, baseline thrombocytosis, multivessel disease, symptom onset-to-balloon time, and total stent length. Randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting versus bare metal stents were not significant predictors of reinfarction. Reinfarction was a powerful independent predictor of subsequent cardiac mortality (hazard ratio [95% confidence interval]=7.65 [4.47-13.09]; P<0.0001) and all-cause mortality (hazard ratio [95% confidence interval]=2.88 [1.74-4.78]; P<0.0001).. Despite advances in pharmacotherapy and stents, reinfarction after primary percutaneous coronary intervention is not infrequent, in the contemporary era is most often attributable to stent thrombosis, and is strongly associated with subsequent cardiac and all-cause mortality. Further enhancements in drugs and devices to prevent reinfarction are needed to improve outcomes in high-risk patients with ST-segment-elevation myocardial infarction.. http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Topics: Acute Disease; Aged; Antithrombins; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Prospective Studies; Recombinant Proteins; Recurrence; Risk Factors; Survival Analysis; Thrombosis; Treatment Outcome

The effectiveness of bivalirudin in patients undergoing percutaneous coronary intervention for acute myocardial infarction has been tested in clinical trials, but its use in a real-world scenario has never been reported.. From the total number of patients enrolled in the EUROVISION registry, 678 subjects affected by ST-elevation myocardial infarction were selected and included in the analysis. Posology and usage patterns of bivalirudin, as evaluated by dose and time of drug bolus and infusion administered, were evaluated. The 30-day outcome has been assessed by efficacy and safety endpoints.. All patients received an initial intravenous bolus of bivalirudin (0.70±0.25 mg/kg) followed by an infusion (1.58±0.47 mg/kg/h; duration: 60 [30, 107] min) in 99.3% of cases. An additional bolus (0.49±0.06 mg/kg) was administered in 9.3% of patients. Bivalirudin infusion was prolonged after procedure in 62.2%. Death occurred in 2.1% of patients, non-fatal myocardial reinfarction in 0.3%, unplanned revascularization in 0.6% and non-fatal stroke in 0.4%. Acute stent thrombosis was not observed. Major bleeding occurred in 1.5% of patients.. Bivalirudin usage in the setting of primary PCI provided excellent results in terms of 30-day outcome even in a real-world population.

Topics: Adult; Aged; Aged, 80 and over; Antithrombins; Electrocardiography; Europe; Female; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Registries; Risk Factors; Treatment Outcome

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

Transradial intervention (TRI) and bivalirudin infusion compared with transfemoral coronary intervention or unfractionated heparin plus glycoprotein IIb/IIIa inhibitors decrease bleeding complications in patients with acute coronary syndromes (ACS). Although bleeding is thought to be associated with worse outcomes, it remains unclear whether TRI and bivalirudin both independently lower ischemic or combined ischemic and bleeding complications in ACS patients undergoing contemporary invasive management.. The primary objectives of the MATRIX program are to assess whether TRI or bivalirudin as compared, respectively, with transfemoral coronary intervention (MATRIX access site) or unfractionated heparin plus provisional glycoprotein IIb/IIIa inhibitors, (MATRIX antithrombin) decrease the 30-day incidence of an ischemic (ie, death, myocardial infarction or stroke) or an ischemic and bleeding composite end point across the whole spectrum of ACS patients, including clarifying the optimal duration of bivalirudin infusion after percutaneous coronary intervention (MATRIX treatment duration).. The MATRIX (NCT01433627) study, which incorporates 3 randomized comparisons in a nonfactorial manner and primary end points at 30 days and clinical follow-up ≤ 1 year, is a large-scale, multicenter study with blind event adjudication conducted at approximately 100 European sites. With 8,200 patients in the randomized comparison of access sites and 6,800 individuals participating in the randomized comparison of antithrombin regimens, this study will have ≥ 85% power for the primary end points.. The MATRIX program aims at conclusively ascertaining the role of TRI and bivalirudin infusion in the whole spectrum of ACS patients undergoing contemporary invasive management.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Europe; Female; Femoral Artery; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Hemorrhage; Radial Artery; Recombinant Proteins; Stroke; Survival Analysis; Treatment Outcome

Thirty-day results of the double-blind, randomised Intracoronary Stenting and Antithrombotic Regimen -Rapid Early Action for Coronary Treatment (ISAR-REACT) 4 trial showed no difference in ischaemic complications and a reduction in bleeding by bivalirudin versus abciximab and heparin in 1,721 patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). A longer follow-up may be required to assess the whole potential benefit of a periprocedural antithrombotic therapy.. The primary outcome for this analysis was the composite of death, myocardial infarction or target vessel revascularisation one year after randomisation. Secondary outcome was the composite of death or myocardial infarction. At one year, the primary outcome occurred in 21.3% of patients assigned to abciximab and heparin versus 21.5% assigned to bivalirudin (hazard ratio [HR] 0.99; 95% confidence interval [CI]: 0.80-1.21; p=0.94). The combined incidence of death or myocardial infarction was 15.7% in the abciximab and heparin group versus 16.0% in the bivalirudin group (HR 0.99; 95% CI: 0.78-1.26; p=0.94). The mortality rates were 4.0% and 4.7%, respectively (HR 0.85; 95% CI: 0.54-1.34; p=0.48). At one year, no significant differences in the primary outcome were observed with abciximab and heparin versus bivalirudin in any of the subgroups analysed.. In patients with NSTEMI undergoing PCI, abciximab with heparin and bivalirudin provide comparable outcomes at one year, although bivalirudin reduced the rate of bleeding at 30 days.. URL www.clinicaltrials.gov; Unique identifier NCT00373451.

Topics: Abciximab; Aged; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Double-Blind Method; Drug Combinations; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Treatment Outcome

The present substudy from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial assessed the outcomes and their relation to different antithrombotic regimens in patients with previous coronary artery bypass grafting (CABG) treated with primary percutaneous coronary intervention. Of 3,599 patients with information regarding a history of CABG, 105 (2.9%) had previously undergone CABG. Of these 105 patients, 46 were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor and 59 to bivalirudin. The patients with versus without previous CABG were less frequently triaged to primary percutaneous coronary intervention (83.8% vs 93.2%, p = 0.0002) and had a longer door-to-balloon time (median 1.9 vs 1.6 hours, p = 0.047), lower rates of final Thrombolysis In Myocardial Infarction flow grade 2 to 3 in the intervened vessel (92.6% vs 97.8%, p = 0.007), and less frequent rates of complete or partial ST-segment resolution (66.3% vs 77.6%, p = 0.019). At 3 years, previous CABG was associated with a significantly greater incidence of major adverse cardiovascular events (36.4% vs 21.4%, p <0.001) owing to greater rates of mortality (11.2% vs 6.7%, p = 0.08), reinfarction (11.6% vs 7.1%, p = 0.09), stroke (5.1% vs 1.8%, p = 0.013), and ischemic target vessel revascularization (23.6% vs 12.9%, p = 0.005). The outcomes did not differ significantly as a function of the antithrombotic regimen. On multivariate analysis, previous CABG was an independent predictor of 3-year ischemic stroke (hazard ratio 3.57, 95% confidence interval 1.09 to 11.66). Intervention on the saphenous vein graft versus the native vessel predicted 3-year major adverse cardiovascular events (hazard ratio 2.69, 95% confidence interval 1.17 to 6.19). In the HORIZONS-AMI trial, previous CABG was associated with a delay to mechanical reperfusion and lower rates of percutaneous coronary intervention and patency of the infarct related vessel along with worse clinical outcomes.

Topics: Aged; Antithrombins; Coronary Artery Bypass; Dose-Response Relationship, Drug; Electrocardiography; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Stents; Survival Rate; Thrombolytic Therapy; Time Factors; Treatment Outcome

Female sex independently predicts bleeding risk after percutaneous coronary intervention (PCI). Bivalirudin is safer than abciximab plus heparin in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Thus, a greater benefit of bivalirudin in women would be expected.. We performed a sex-based analysis of the patients with NSTEMI (n = 1,721, 399 women) enrolled in the ISAR-REACT 4 trial and randomized to receive bivalirudin or abciximab plus heparin. Main outcome was a 30-day composite of death, large recurrent myocardial infarction, urgent target vessel revascularization, or major bleeding. Secondary outcome was 1-year composite of death, myocardial infarction, or target vessel revascularization.. No difference in the main outcome was observed in groups with bivalirudin or abciximab plus heparin: 12.6% versus 15.5% (hazard ratio [HR] 0.81, 95% CI 0.48-1.37) among women and 10.6% versus 9.5% (HR 1.12, 95% CI 0.77-1.64) among men. Major bleeding occurred in 4.5% in the bivalirudin group versus 7.5% in the abciximab plus heparin group (HR 0.60, 95% CI 0.26-1.39) among women and 2.0% versus 3.8% (HR 0.52, 0.27-1.02) among men. At 1 year, the secondary outcome was observed in 24.1% in the bivalirudin group versus 28.7% in the abciximab plus heparin group among women, HR of 0.80 (95% CI 0.55-1.17), and in 20.6% and 19.0%, respectively, HR of 1.10 (95% CI 0.86-1.40) among men.. Despite a higher peri-PCI bleeding risk in women, bivalirudin is as effective as and safer than abciximab plus heparin in women and men with NSTEMI undergoing PCI.

Topics: Abciximab; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antithrombins; Female; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins; Sex Factors; Thrombolytic Therapy

Patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) of the left anterior descending artery (LAD) are at increased risk for cardiovascular events compared with patients undergoing non-LAD PCI. We assessed the impact of bivalirudin and paclitaxel-eluting stenting (PES) in patients with STEMI who underwent LAD PCI. In the HORIZONS-AMI trial, 1,445 patients had LAD PCI and 1,884 patients had non-LAD PCI. The 3-year composite rates of death, reinfarction, stroke, or ischemia-driven target vessel revascularization were significantly higher in patients who underwent LAD PCI compared with non-LAD PCI (24.0% vs 20.6%, hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.04 to 1.39, p = 0.013), driven by a statistically significant increase in cardiac death (5.4% vs 2.7%, HR 2.00, 95% CI 1.40 to 2.86, p = 0.001). For patients who underwent LAD PCI, treatment with bivalirudin resulted in significantly lower rates of cardiac death (3.8% vs 6.8%, HR 0.55, 95% CI 0.34 to 0.89, p = 0.01), reinfarction (5.3% vs 9.5%, HR 0.55, 95% CI 0.37 to 0.83, p = 0.004), and major bleeding events (7.3% vs 11.8%, HR 0.60, 95% CI 0.43 to 0.86, p = 0.004) compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitor. Randomization to PES compared with bare-metal stenting resulted in a significant lower rate of target vessel revascularization (13.2% vs 19.8%, HR 0.64, 95% CI 0.47 to 0.86, p = 0.003) with no significant differences in stent thrombosis, reinfarction, or death. In conclusion, in patients with STEMI who underwent primary PCI of LAD, the use of bivalirudin was associated with a reduction in mortality and bleeding rates at 3 years. PES reduced revascularization rates in this population but did not have a significant impact on mortality.

Topics: Aged; Antineoplastic Agents, Phytogenic; Antithrombins; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Treatment Outcome

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

In ISAR-REACT-4 (abciximab and heparin vs. bivalirudin for non-ST-elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of bleeding after percutaneous coronary intervention (PCI) compared with unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of bivalirudin. This analysis examined whether there exists an interaction on bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI.. Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or bivalirudin for PCI. The use of a VCD after femoral access was left to the operator's discretion. The effect of randomized treatment in patients who received a VCD was compared to that in patients with manual compression of the femoral access site. The primary end-point of this analysis was the 30-day incidence of ISAR-REACT-4 major bleeding.. A total of 1,711 patients were enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188 (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR- REACT-4 major bleeding was higher with UFH + abciximab than with bivalirudin, independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7% without VCD, Pint = 0.76). There were also no interactions between randomized treatment and VCDs with respect to any of the ischemic end-points or net clinical outcome (Pint > 0.56).. In patients undergoing PCI for NSTEMI, the reduction of major bleeding by bivalirudin compared with UFH + abciximab was not affected whether a VCD was used.

Topics: Abciximab; Antibodies, Monoclonal; Antithrombins; Blood Loss, Surgical; Collagen; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk Factors; Vascular Closure Devices

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

ST-elevation in lead aVR is known to be associated with a worse prognosis in patients with acute ST elevation myocardial infarction (MI) but the significance of ST depression in lead aVR has been unclear. Infarction of the inferior apex of the left ventricle may not be appreciated on the standard 12-lead electrocardiogram (ECG) except by observing ST depression in lead aVR which is reciprocal to lead V(7). We therefore determined the prognostic value of the full spectrum of aVR ST changes in patients presenting with acute ST elevation MI.. Lead aVR ST level was measured on randomization and 60 min ECGs in 15 315 patients with normal conduction from the HERO-2 trial. The outcome measure was 30-day mortality. aVR ST elevation ≥1 mm was associated with higher 30-day mortality for both inferior (22.5% for ≥1.5 mm and 13.2% for 1 mm) and anterior (23.5% for ≥1.5 mm and 11.5% for 1 mm) infarction. In contrast, deeper aVR ST depression (0, 0.5, 1, and ≥1.5 mm) was associated with higher mortality for anterior infarction (9.8, 13.2, 12.8, and 16.8%, respectively, trend P-value <0.0001) but not for inferior infarction. The resolution of aVR ST depression and ST elevation 60 min after fibrinolysis was associated with lower mortality.. There is a U-shaped relationship between 30-day mortality and aVR ST level in patients presenting with anterior but not inferior ST elevation MI.

Topics: Aged; Antithrombins; Aspirin; Electrocardiography; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Prognosis; Recombinant Proteins; Streptokinase

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

To assess the cost-effectiveness of bivalirudin versus heparin and glycoprotein IIb/IIIa inhibitor (H-GPI) in patients undergoing primary percutaneous coronary intervention (PPCI) for acute ST-segment elevation myocardial infarction (STEMI), from a UK health service perspective.. Cost-utility analysis with life-long time horizon.. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness.. Event risks and medical resource use data derived from the HORIZONS-AMI trial were entered into a decision analytic model. Clinical events until the end of year 1 (main model) or year 3 (alternative model) were modelled in detail. Adjustments were applied to approximate UK routine practice characteristics. Life expectancy of 1-year or 3-year survivors, health-state utilities, initial hospitalisation length of stay in the comparator strategy and unit costs were based on UK sources. Costs and effects were discounted at 3.5%.. The main model predicted bivalirudin and H-GPI patients to survive 11.52 and 11.35 (undiscounted) years on average, respectively, and to accrue 6.26 and 6.17 QALYs. Patient lifetime costs were £267 lower in the bivalirudin strategy (£12 843 vs £13 110). Extensive sensitivity and scenario analyses confirmed these results to be robust. In probabilistic analysis, quality-adjusted survival was higher and costs were lower with bivalirudin in 95.0% of simulation runs. In 99.2%, cost-effectiveness was better than £20 000 per QALY gained. Results from the alternative model were fully consistent.. The use of bivalirudin instead of H-GPI in STEMI patients undergoing PPCI is cost-effective, and offers a high probability of dominance. Background treatment with aspirin and clopidogrel is assumed.

Topics: Aged; Anticoagulants; Cost-Benefit Analysis; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Quality-Adjusted Life Years; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome

Elevation of baseline cardiac troponin in patients presenting with acute coronary syndromes (ACS) confers an adverse prognosis. The prognostic value of troponin elevation in patients with chronic kidney disease (CKD) and ACS is less certain.. In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategy) trial, 13 819 patients with moderate and high-risk ACS were assigned randomly to receive heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin monotherapy. Among 2179 patients with CKD (creatinine clearance <60 mL/min), baseline troponin elevation was present in 1291 patients (59.2%). Major bleeding and major adverse cardiac events (MACE), including death, myocardial infarction (MI), or unplanned revascularization, were examined according to baseline troponin status and randomization arm. Patients with CKD in whom the baseline troponin level was elevated had significantly higher rates of death, MI, and MACE at 30 days and 1 year compared with CKD patients without elevated baseline troponin. By multivariable analysis, baseline troponin elevation in patients with CKD was an independent predictor of composite death or MI at 30 days (hazard ratio [95% CI]=2.05 [1.48, 2.83], P<0.0001) and 1 year (1.72 [1.36, 2.17], P<0.0001). In CKD patients with baseline troponin elevation, bivalirudin monotherapy compared with heparin plus a GPI significantly reduced the 30-day rates of major bleeding with nonsignificantly different rates of MACE at 30 days and 1 year.. In patients with ACS and CKD, baseline troponin elevation is associated with significantly worse short- and long-term clinical outcomes. Bivalirudin monotherapy safely reduces major bleeding in ACS patients with CKD and baseline troponin elevation.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Biomarkers; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Male; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prognosis; Recombinant Proteins; Reference Standards; Survival Analysis; Troponin T

The study sought to determine whether rapid access to medical care and reperfusion results in a better prognosis in patients with in-hospital compared with out-of-hospital stent thrombosis (ST) in patients with ST-segment elevation myocardial infarction (STEMI) in the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial.. Whether the prognosis of in-hospital and out-of-hospital ST are similar is uncertain, with conflicting data reported from prior studies.. A total of 3,602 STEMI patients undergoing primary percutaneous coronary intervention (PCI) were randomized to bivalirudin (n = 1,800) versus unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) (UFH+GPI; n = 1,802). Stents were implanted in 3,202 patients, 156 (4.9%) of whom developed Academic Research Consortium definite/probable ST during 3-year follow-up. We investigated the 1-year clinical outcomes after ST in 54 patients with in-hospital ST compared with 102 patients with out-of-hospital ST.. One year after the ST event, patients with in-hospital compared with out-of-hospital ST had significantly greater mortality (27.8% vs. 10.8%, p < 0.01); most deaths in both groups occurred within 1 week of the ST event. Patients with in-hospital ST also had higher rates of major bleeding (21.2% vs. 6.0%, p < 0.01), but a lower rate of myocardial infarction (56.6% vs. 77.5%, p < 0.01). Subgroup analysis within both in-hospital and out-of-hospital ST groups indicated that subacute ST had the highest mortality. By multivariable analysis, 1-year mortality was significantly increased in patients with in-hospital compared with out-of-hospital ST (adjusted hazard ratio: 4.62, 95% confidence interval: 1.98 to 10.77, p < 0.01). Additional correlates of increased mortality after an ST event included diabetes and randomization to UFH+GPI (vs. bivalirudin).. Following primary PCI for STEMI, more than one-third of all ST events during 3-year follow-up occurred during the index hospital phase. Mortality and major bleeding were significantly higher after in-hospital ST compared with out-of-hospital ST. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

Topics: Aged; Female; Follow-Up Studies; Hirudins; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Stents; Thrombosis; Treatment Outcome

Bivalirudin, a direct thrombin inhibitor, is as effective as unfractionated heparin (UFH), with decreased bleeding in patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI). The aim of this study was to evaluate the effectiveness of bivalirudin versus UFH in selected PCI patients at high bleeding risk. Four hundred one consecutive patients who underwent PCI fulfilling ≥ 1 enrollment criterion (age >75 years, chronic renal failure, and diabetes mellitus) were randomized to bivalirudin (bolus 0.75 mg/kg followed by infusion during the procedure; n = 198) or UFH (75 IU/kg; n = 203). In the overall population, 39% were aged >75 years, 22% had renal failure, 63% had diabetes, and 29% had acute coronary syndromes. The primary efficacy end point was the 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization). The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI. All patients were preloaded with clopidogrel 600 mg. Glycoprotein IIb/IIIa inhibitors were used at the operators' discretion. Thirty-day major adverse cardiac event rates were 11.1% in the bivalirudin group and 8.9% in the UFH group (p = 0.56); the primary efficacy end point was reached mainly because of periprocedural myocardial infarction; 1 patient in the bivalirudin group had stent thrombosis. Occurrence of the primary safety end point was 1.5% in the bivalirudin group and 9.9% in the UFH group (p = 0.0001); this benefit was essentially driven by the prevention of entry-site hematomas >10 cm (0.5% vs 6.9%, p = 0.002). In conclusion, Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin (ARMYDA-7 BIVALVE) indicates that bivalirudin, compared with UFH, causes significantly lower bleeding and has a similar incidence of major adverse cardiac events in patients with older age, diabetes mellitus, or chronic renal failure who undergo PCI.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Artery Disease; Diabetes Complications; Drug Therapy, Combination; Female; Heart Diseases; Heparin; Hirudins; Humans; Incidence; Male; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Renal Insufficiency; Treatment Outcome

The ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy aimed to determine the relevance of high on-clopidogrel treatment platelet reactivity (HPR) in non-ST-segment elevation myocardial infarction patients that received abciximab with unfractionated heparin (UFH) or bivalirudin during percutaneous coronary intervention (PCI).. In patients undergoing PCI, HPR has been linked to a higher risk for ischemic events. The influence of HPR on clinical outcomes may differ with regard to the adjunctive antithrombotic treatment administered. In ISAR-REACT 4, bivalirudin treatment showed similar efficacy profiles as compared to abciximab with UFH. The impact of HPR on clinical outcomes in abciximab with UFH versus bivalirudin treated non-ST-segment elevation myocardial infarction patients has never been investigated specifically.. A total of 564 patients (274 in abciximab/UFH group vs. 290 in bivalirudin group) were enrolled in this study. Presence or absence of HPR following clopidogrel loading was determined by platelet function testing on a Multiplate analyzer (Verum Diagnostica, Munich, Germany). Per study group and stratified in HPR and no-HPR patients, the 30-day incidence of a combined efficacy endpoint (death, myocardial infarction, urgent target vessel revascularization) was determined.. For abciximab with UFH, the incidence of the efficacy endpoint was similar in HPR versus no-HPR patients (9.4% vs. 6.7%; odds ratio: 1.4; 95% confidence interval: 0.6 to 3.5; p = 0.43). For bivalirudin, the incidence of the efficacy endpoint was significantly higher in HPR versus no-HPR patients (22.0% vs. 5.0%; odds ratio: 5.4; 95% confidence interval: 2.4 to 12.1; p < 0.0001).. For patients with a risk profile similar to the subjects enrolled in this platelet substudy, the impact of HPR on clinical outcomes may depend on the type of adjunctive antithrombotic therapy used during PCI. Further investigations are warranted to clarify whether assessment of platelet function may help tailoring antithrombotic therapy during PCI.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Clopidogrel; Cohort Studies; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prognosis; Recombinant Proteins; Signal Processing, Computer-Assisted; Stents; Survival Analysis; Ticlopidine

Thrombolysis In Myocardial Infarction (TIMI) flow and Myocardial Blush Grade (MBG) are important prognostic indicators before and after primary percutaneous coronary intervention (PCI) in ST-segment-elevation myocardial infarction; however, the concordance and relative prognostic utility of operator (Op) versus angiography core laboratory (ACL) assessed TIMI flow and MBG are unknown.. Baseline and final Op and ACL TIMI flow and MBG assessment were compared from the Harmonizing Outcomes with RevascularIZatiON and Stents in AMI trial in 3345 patients undergoing primary PCI using Cohen's κ coefficient. κ Was highest for pre-PCI TIMI flow (0.51, representing moderate agreement) and lowest for post-PCI MBG (0.20, representing fair agreement). Discordance between Op and ACL for final TIMI flow (0 to 2 versus 3) occurred in 12.9% of patients and for final MBG (0 to 1 versus 2 to 3) in 22.4%. Among 415 patients with final TIMI flow 0 to 2 by ACL, Op scoring was TIMI flow 3 in 267 (64.3%). Similarly, among 706 patients with final MBG 0 to 1 by ACL, 563 (79.7%) were classified as MBG 2 to 3 by Op. Post-PCI TIMI 3 flow and MBG 2 to 3 strongly correlated with 3-year survival, as assessed by both Op and ACL (P<0.0001). Mortality was intermediate in patients in whom ACL and Op were discordant, without marked prognostic differences between the discordant groups.. Op and ACL assessment of angiographic markers of reperfusion in ST-segment-elevation myocardial infarction demonstrates fair to moderate agreement. Op tended to favorably grade unfavorable ACL results. Nonetheless, both Op and ACL assessment of reperfusion strongly inform prediction of 3-year mortality.

Topics: Aged; Anticoagulants; Antithrombins; Coronary Angiography; Coronary Circulation; Drug-Eluting Stents; Electrocardiography; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Observer Variation; Paclitaxel; Peptide Fragments; Percutaneous Coronary Intervention; Predictive Value of Tests; Prognosis; Recombinant Proteins; Tubulin Modulators

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

This study sought to assess the contemporary outcomes of patients with prior coronary artery bypass graft (CABG) who present with moderate and high-risk acute coronary syndromes (ACS) and are treated with an early invasive strategy and contemporary antithrombin regimens.. The prognosis of patients with ACS and prior CABG in relation to triage strategy and contemporary antithrombotic regimens is unknown.. In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 2,475 of 13,764 patients (18.0%) with ACS managed with an early invasive strategy had previously undergone CABG. Their outcomes were examined according to treatment and randomized antithrombin regimen.. Prior CABG was associated with older age, more frequent comorbidities, higher Thrombolysis In Myocardial Infarction risk score, and lower left ventricular ejection fraction. Patients with versus without prior CABG were less likely to undergo (repeat) CABG and were more likely to be managed medically. At 1 year, patients with versus without prior CABG had higher rates of major adverse cardiac events (MACE) (22.5% vs. 15.2%, p < 0.0001) due to greater mortality (5.4% vs. 3.9%, p < 0.0001), myocardial infarction (10.0% vs. 6.8%, p < 0.0001), and unplanned revascularization (13.1% vs. 8.2%, p < 0.0001). History of CABG was an independent predictor of MACE. The 1-year MACE rates were not significantly different after randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (odds ratio: 1.24, 95% confidence interval: 0.90 to 1.70).. Despite the progress in the treatment of coronary artery disease, patients with prior CABG and ACS have a poor prognosis, substantially worse than for those without prior CABG. Whereas bivalirudin monotherapy was an acceptable treatment for these patients, it did not improve their prognoses.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Comorbidity; Coronary Angiography; Coronary Artery Bypass; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Reoperation; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

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 standard of care for STEMI PCI for the past decade has been aspirin, clopidogrel, heparin, and a glycoprotein IIbIIIa receptor inhibitor (GPI). A bivalirudin strategy was shown to be superior to a GPI strategy in the HORIZONS AMI trial for net adverse clinical events (combined MACE and bleeding). An increased risk of acute stent thrombosis in the bivalirudin arm may have prevented broader adoption of bivalirudin for this indication. We hypothesized that acute stent thrombosis risk could be ameliorated by a 2 h infusion of bivalirudin following STEMI PCI. We implemented a multicenter, prospective registry for all STEMI patients in Vermont treated at a single PCI center. Each patient was routinely pre-loaded with dual antiplatelet therapy and 75% received an unfractionated heparin bolus prior to PCI. The utilization of bivalirudin bolus and continued 2 h infusion after PCI was routine with GPI bailout optional. 128 consecutive STEMI patients underwent primary PCI from October 1, 2008 to September 30, 2009. 92% of primary PCI patients received bivalrudin during and after the procedure with a 9% rate of bail out GPI. There was one case of probable or definite acute stent thrombosis (0.7%), and this single case occurred despite use of bailout GPI. Despite the prolonged infusion of bivalirudin, major bleeding occurred in only 1.7% of STEMI patients. In conclusion, prolonging bivalirudin for 2 h after STEMI PCI may be a promising method to alleviate acute stent thrombosis risk without losing the bleeding complication benefit of the bivalirudin strategy.

Topics: Aged; Antithrombins; Coronary Artery Bypass; Female; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins; Registries; Stents; Thrombosis; Time Factors

Whether thrombus aspiration and local glycoprotein IIb/IIIa administration reduce infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has not been established in multicenter studies.. INFUSE-AMI is a multicenter, open-label, controlled, single-blind randomized study enrolling 452 subjects with anterior STEMI and an occluded proximal or mid-left anterior descending artery with thrombosis in myocardial infarction 0, 1, or 2 grade flow undergoing primary PCI with bivalirudin anticoagulation. Subjects are randomized in a 2 × 2 factorial to one of the following 4 arms: (1) local infusion of abciximab using the ClearWay RX Local Therapeutic Infusion Catheter (ClearWay, Atrium Medical Corp, Hudson, NH) after aspiration with a 6F Export Aspiration Catheter (Medtronic, Inc, Minneapolis, MN), (2) local infusion of abciximab using the ClearWay RX Infusion Catheter and no aspiration, (3) no local infusion of abciximab and aspiration with a 6F Export Aspiration Catheter, or (4) no local infusion of abciximab and no aspiration. The primary end point is infarct size (percentage of total left ventricular mass) at 30 days measured by cardiac magnetic resonance imaging. Other secondary end points include microvascular obstruction by cardiac magnetic resonance imaging at 5 days, ST-segment resolution, angiographic myocardial perfusion, thrombus burden, angiographic complications, and clinical events through 1-year follow-up. Safety end points include major and minor bleeding.. INFUSE-AMI is testing the hypothesis that the intracoronary administration of an abciximab bolus with or without thrombus aspiration before stent implantation compared to no infusion with or without thrombus aspiration reduces infarct size among patients undergoing primary PCI for anterior STEMI who are treated with bivalirudin.

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antithrombins; Coronary Occlusion; Coronary Thrombosis; Endpoint Determination; Hirudins; Humans; Immunoglobulin Fab Fragments; Infusions, Intra-Arterial; Magnetic Resonance Imaging, Cine; Myocardial Infarction; Patient Selection; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins; Research Design; Thrombectomy

Concerns persist regarding the risk of stent thrombosis in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.. The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial included 3602 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention who were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) (n=1802) versus bivalirudin monotherapy (n=1800). Stents were implanted in 3202 patients, including 2261 who received drug-eluting stents and 861 who received only bare metal stents. Definite or probable stent thrombosis within 2 years occurred in 137 patients (4.4%), including 28 acute events (0.9%), 49 subacute events (1.6%), 32 late events (1.0%), and 33 very late events (1.1%). The 2-year cumulative rates of stent thrombosis were 4.4% with both drug-eluting stents and bare metal stents (P=0.98) and 4.3% versus 4.6% in patients randomized to bivalirudin monotherapy versus heparin plus a GPI, respectively (P=0.73). Acute stent thrombosis occurred more frequently in patients assigned to bivalirudin compared with heparin plus a GPI (1.4% versus 0.3%; P<0.001), whereas stent thrombosis after 24 hours occurred less frequently in patients with bivalirudin compared with heparin plus a GPI (2.8% versus 4.4%; P=0.02). Pre-randomization heparin and a 600-mg clopidogrel loading dose were independent predictors of reduced acute and subacute stent thrombosis, respectively.. Stent thrombosis is not uncommon within the first 2 years after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction, and occurs with similar frequency in patients receiving drug-eluting stents versus bare metal stents and bivalirudin alone versus heparin plus a GPI. Optimizing adjunct pharmacology including early antithrombin therapy preloading with a potent antiplatelet therapy may further reduce stent thrombosis in ST-segment elevation myocardial infarction.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clopidogrel; Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Drug-Eluting Stents; Female; Heparin; Hirudins; Humans; Male; Metals; Middle Aged; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Aggregation Inhibitors; Predictive Value of Tests; Recombinant Proteins; Risk Factors; Ticlopidine; Treatment Outcome; Tubulin Modulators

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 investigated the outcomes of switching to bivalirudin after initial administration of heparin in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.. Unfractionated heparin (UFH) is frequently administered early in ST-segment elevation myocardial infarction. Whether the benefits of bivalirudin documented in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial persist in patients previously administered UFH is unknown.. We analyzed the outcomes of the 2,357 patients from HORIZONS-AMI treated with UFH before enrollment according to their subsequent randomization to bivalirudin (switch group, n = 1,178) or UFH plus a glycoprotein IIb/IIIa inhibitor (control group, n = 1,179).. At 30 days, major bleeding occurred in 7.6% of the switch group versus 12.3% of the control group (p = 0.0001). Switch patients had lower 30-day rates of cardiac mortality (1.6% vs. 2.9%, p = 0.04). At 2-year follow-up, switch patients experienced lower rates of major bleeding (8.4% vs. 13.0%, p = 0.0003), cardiac mortality (2.3% vs. 3.8%, p = 0.04), and reinfarction (4.0% vs. 7.1%, p = 0.0002). Two-year rates of definite/probable stent thrombosis were similar in switch and control patients (3.1% vs. 4.3%, p = 0.17).. In ST-segment elevation myocardial infarction patients who receive early treatment with UFH, switching to bivalirudin before primary percutaneous coronary intervention results in reduced rates of major bleeding and improved early and late cardiac survival.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Treatment Outcome

Primary results of the HORIZONS-AMI trial have been previously reported. In this final report, we aimed to assess 3-year outcomes.. HORIZONS-AMI was a prospective, open-label, randomised trial undertaken at 123 institutions in 11 countries. Patients aged 18 years or older were eligible for enrolment if they had ST-segment elevation myocardial infarction (STEMI), presented within 12 h after onset of symptoms, and were undergoing primary percutaneous coronary intervention. By use of a computerised interactive voice response system, we randomly allocated patients 1:1 to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI; pharmacological randomisation; stratified by previous and expected drug use and study site) and, if eligible, randomly allocated 3:1 to receive a paclitaxel-eluting stent or a bare metal stent (stent randomisation; stratified by pharmacological group assignment, diabetes mellitus status, lesion length, and study site). We produced Kaplan-Meier estimates of major adverse cardiovascular events at 3 years by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00433966.. Compared with 1802 patients allocated to receive heparin plus a GPI, 1800 patients allocated to bivalirudin monotherapy had lower rates of all-cause mortality (5·9%vs 7·7%, difference -1·9% [-3·5 to -0·2], HR 0·75 [0·58-0·97]; p=0·03), cardiac mortality (2·9%vs 5·1%, -2·2% [-3·5 to -0·9], 0·56 [0·40-0·80]; p=0·001), reinfarction (6·2%vs 8·2%, -1·9% [-3·7 to -0·2], 0·76 [0·59-0·99]; p=0·04), and major bleeding not related to bypass graft surgery (6·9%vs 10·5%, -3·6% [-5·5 to -1·7], 0·64 [0·51-0·80]; p=0·0001) at 3 years, with no significant differences in ischaemia-driven target vessel revascularisation, stent thrombosis, or composite adverse events. Compared with 749 patients who received a bare-metal stent, 2257 patients who received a paclitaxel-eluting stent had lower rates of ischaemia-driven target lesion revascularisation (9·4%vs 15·1%, -5·7% [-8·6 to -2·7], 0·60 [0·48-0·76]; p<0·0001) after 3 years, with no significant differences in the rates of death, reinfarction, stroke or stent thrombosis. Stent thrombosis was high (≥4·5%) in both groups.. The effectiveness and safety of bivalirudin monotherapy and paclitaxel-eluting stenting are sustained at 3 years for patients with STEMI undergoing primary percutaneous coronary intervention.. Boston Scientific and The Medicines Company.

Topics: Angioplasty, Balloon; Combined Modality Therapy; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Stents; Survival Analysis; Time Factors; Treatment Outcome

We sought to evaluate the safety and efficacy of bivalirudin compared with glycoprotein IIb/IIIa inhibitors (GPI) in diabetic patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).. Prior studies have demonstrated that GPI are especially beneficial in patients with diabetes with acute coronary syndromes and/or those undergoing PCI.. In the multicenter, prospective HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients with STEMI were randomized to bivalirudin or unfractionated heparin plus a GPI. Clinical outcomes were analyzed at 30 days and 1 year in patients with diabetes.. Diabetes mellitus was present in 593 patients (16.5%). The rates of cardiac death were significantly lower in diabetic patients treated with bivalirudin compared with heparin plus GPI (30 days: 2.1% vs. 5.5%, p = 0.04; 1 year: 2.5% vs. 7.1%, p = 0.01), and bivalirudin resulted in lower 30-day rates of stroke (0% vs. 2%, p = 0.02). There were no significant differences among diabetic patients randomized to bivalirudin versus heparin plus GPI in the 1-year rates of major adverse cardiac events (14.2% vs. 16.2%, p = 0.44), major bleeding (8.7% vs. 10.7%, p = 0.42), or stent thrombosis (4.2% vs. 3.8%, p = 0.85). By interaction testing, the relative effects of bivalirudin compared with heparin plus GPI were not significantly different in patients with and without diabetes.. In patients with diabetes mellitus presenting with STEMI undergoing primary PCI, anticoagulant therapy with bivalirudin compared with heparin plus GPI is safe and effective and might reduce cardiac mortality at 30 days and 1 year. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Angiography; Diabetes Mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Hirudins; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Prospective Studies; Recombinant Proteins; Stents; Survival Rate; Time Factors; Treatment Outcome

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

Bivalirudin is commonly used during percutaneous coronary intervention (PCI) rather than unfractionated heparin. The higher cost of bivalirudin may be offset if it reduces costly bleeding complications and/or length of stay. We sought to assess the effect of using bivalirudin on the costs of care among patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI.. We analyzed data from 64,872 patients treated in 1 of 278 hospitals. The effect of overall hospital use of bivalirudin on clinical and economic outcomes was assessed using multivariable regression, based on average hospital use of treatments.. The use of bivalirudin among patients with STEMI treated with PCI varied widely across hospitals, with a median of 6.9% (interquartile range 2.3%-18.6%). After controlling for patient and hospital characteristics, use of bivalirudin rather than heparin and a glycoprotein IIb/IIIa inhibitor reduced bleeding (odds ratio 0.47, P < .001), length of stay (-0.47 days, P < .03), and hospital costs (-14%, P < .04).. Use of bivalirudin among patients with STEMI treated with PCI appears to reduce bleeding and overall costs.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Electrocardiography; Female; Follow-Up Studies; Health Care Costs; Hirudins; Humans; Incidence; Length of Stay; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Postoperative Hemorrhage; Recombinant Proteins; Retrospective Studies; Treatment Outcome

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

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

We sought to determine whether a transradial (TR) approach compared with a transfemoral (TF) approach was associated with improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) in a post hoc analysis of the HORIZONS-AMI trial. There is a paucity of data comparing the TR approach with the TF approach in patients with STEMI treated with primary PCI and contemporary anticoagulant regimens.. In HORIZONS-AMI, primary PCI for STEMI was performed in 3,340 patients, either by the TR (n=200) or TF approach (n=3,134). Endpoints included the 30-day and one-year rates of major adverse cardiovascular events (MACE: death, reinfarction, stroke or target vessel revascularisation), non CABG-related major bleeding, and net adverse clinical events (NACE: MACE or major bleeding). TR compared to TF access was associated with significantly lower 30-day rates of composite death or reinfarction (1.0% vs. 4.3%, OR 0.23, 95% CI [0.06,0.94], p=0.02), non CABG-related major bleeding (3.5% vs. 7.6%, OR 0.45, 95% CI [0.21,0.95], p=0.03), MACE (2.0% vs. 5.6%, OR 0.35, 95% CI [0.13,0.95], p=0.02), and NACE (5.0% vs. 11.6%,OR 0.42, 95% CI [0.22,0.78], p<0.01). At one year, the TR group still had significantly reduced rates of death or reinfarction (4.0% vs. 7.8%, OR 0.51, 95% CI [0.25,1.02], p=0.05), non CABG-related major bleeding (3.5% vs. 8.1%, OR 0.42, 95% CI [0.20,0.89], p=0.02), MACE (6.0% vs. 12.4%, OR 0.47, 95% CI [0.26,0.83], p<0.01) and NACE (8.5% vs. 17.8%, OR 0.45, 95% CI [0.28,0.74], p<0.001). By multivariable analysis, TR access was an independent predictor of freedom from MACE and NACE at 30 days and one year.. In patients with STEMI undergoing primary PCI with contemporary anticoagulation regimens in the HORIZONS-AMI trial, a TR compared with a TF approach was associated with reduced major bleeding and improved event-free survival.

Topics: Aged; Angioplasty; Antithrombins; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Prospective Studies; Radial Artery; Recombinant Proteins; Thrombosis; Treatment Outcome

In ISAR-REACT 3, 30-day outcomes in 4570 biomarker negative patients undergoing percutaneous coronary intervention (PCI) > or =2 h after pre-treatment with 600 mg of clopidogrel revealed less bleeding with bivalirudin compared with unfractionated heparin, but no difference in 30-day net clinical benefit. The objective of the present analysis was to assess the impact of bivalirudin vs. heparin on 1-year outcomes in ISAR-REACT 3.. The primary outcome for this analysis was the composite of death, myocardial infarction, or target vessel revascularization 1 year after randomization. The composite of death or myocardial infarction was a secondary outcome. At 1 year, the primary outcome occurred in 17.1% of patients assigned to bivalirudin vs. 17.5% assigned to heparin [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.86-1.13; P = 0.816]. The combined incidence of death or myocardial infarction was 7.7% in the bivalirudin group vs. 6.7% in the heparin group (HR, 1.15; 95% CI, 0.93-1.43; P = 0.200). The mortality rate was 1.9% in the bivalirudin group and 1.7% in the heparin group (HR, 1.10; 95% CI, 0.71-1.70; P = 0.667). At 1 year, no significant differences in the primary outcome were observed with bivalirudin and heparin in any of the subgroups analysed.. Bivalirudin and unfractionated heparin during PCI provide comparable outcomes at 1 year in biomarker negative patients undergoing PCI after pre-treatment with 600 mg of clopidogrel.. URL www.clinicaltrials.gov; Unique identifier NCT00262054.

Topics: Angina Pectoris; Angioplasty; Anticoagulants; Death, Sudden, Cardiac; Double-Blind Method; Female; Heparin; Hirudins; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Recombinant Proteins; Treatment Outcome

The aim of this study was to assess the impact of baseline anemia on the outcomes of patients with ST elevation myocardial infarctions who underwent primary percutaneous coronary intervention in relation to contemporary adjunctive antithrombotic therapy and gender. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients were randomized to bivalirudin alone or to unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor before primary percutaneous coronary intervention. Outcomes were assessed at 30 days and 1 year according to anemia and gender. Baseline anemia was present in 331 of 3,153 patients (10.5%). Patients with versus without baseline anemia had a more than twofold increase in major bleeding at 30 days (13.5% vs 6.7%, p <0.0001) and at 1 year (14.8% vs 7.2%, p <0.0001), an association that on multivariate analysis was independent of gender. Mortality was significantly higher in men with versus without baseline anemia (4.6% vs 1.8% at 30 days, p = 0.003; 8.9% vs 3.0% at 1 year, p <0.0001) but not in women (5.3% vs 3.6% at 30 days, p = 0.42; 7.5% vs 5.9% at 1 year, p = 0.54). On multivariate analysis, anemia independently predicted 1-year all-cause mortality in men but not in women. Bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor resulted in twofold lower rates of all-cause and cardiac mortality and major bleeding in patients without but not in those with baseline anemia. In conclusion, baseline anemia was associated with increased major bleeding and death in patients with ST elevation myocardial infarctions who underwent primary PCI but was a stronger predictor of early and late mortality in men than in women. Paradoxically, in this post hoc analysis, the reductions in major bleeding and mortality in ST elevation myocardial infarction afforded by bivalirudin occurred primarily in patients without baseline anemia.

Topics: Aged; Anemia; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Drug Therapy, Combination; Electrocardiography; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Neoadjuvant Therapy; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Probability; Proportional Hazards Models; Recombinant Proteins; Risk Assessment; Sex Factors; Survival Analysis; Thrombolytic Therapy; Treatment Outcome

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

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated whether presentation of patients with STEMI to a noninterventional facility requiring transfer for primary PCI compared to direct admission to a PCI center has an impact on clinical outcomes. Of 3,602 patients enrolled in the multicenter, prospective HORIZONS-AMI trial, 988 (24.7%) were transferred for primary PCI and 2,614 were directly admitted to an interventional hospital. Clinical outcomes at 30 days and 1 year were evaluated. Median time to reperfusion in patients with transfer was 67 minutes longer compared to patients without transfer (272 vs 205 minutes, p <0.001), and first door-to-balloon time was 47 minutes longer (134 vs 87 minutes, p <0.001). At 30 days and 1 year there were no significant differences between patients with and without transfer in the rates of major adverse cardiac events (30 days 5.8% vs 5.4%, p = 0.68; 1 year 11.6% vs 12.0%, p = 0.74), major bleeding (30 days 7.3% vs 6.9%, p = 0.66; 1 year 7.9% vs 7.4%, p = 0.63), or mortality (30 days 2.6% vs 2.6%, p = 0.92; 1 year 4.0% vs 4.2%, p = 0.81). In transfer and nontransfer patients use of bivalirudin compared to unfractionated heparin plus glycoprotein IIb/IIIa inhibitor was associated with lower rates of bleeding, cardiac death, and net adverse clinical events. In conclusion, in the HORIZONS-AMI trial, 30-day and 1-year survival rates and clinical outcomes were comparable in patients with STEMI requiring and not requiring transfer for primary PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Chi-Square Distribution; Coronary Angiography; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Patient Transfer; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Statistics, Nonparametric; Survival Rate; Time Factors; Treatment Outcome

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

The primary objective of this study was to compare the effect of therapy with bivalirudin alone versus bivalirudin plus eptifibatide on platelet reactivity measured by turbidometric aggregometry and thrombin-induced platelet-fibrin clot strength (TIP-FCS) measured by thrombelastography in percutaneous coronary intervention (PCI) patients. The secondary aim was to study the relation of platelet aggregation and TIP-FCS to the occurrence of periprocedural infarction.. Bivalirudin is commonly administered alone to clopidogrel naïve (CN) patients and to patients on maintenance clopidogrel therapy (MT) undergoing elective stenting. The effect of adding eptifibatide to bivalirudin on platelet reactivity (PR) and TIP-FCS, and their relation to periprocedural infarction in these patients are unknown.. Patients (n = 200) stratified to clopidogrel treatment status were randomly treated with bivalirudin (n = 102) or bivalirudin plus eptifibatide (n = 98). One hundred twenty-eight CN patients were loaded with 600 mg clopidogrel immediately after stenting, and 72 MT patients were not loaded. The PR, TIP-FCS, and myonecrosis markers were serially determined.. In CN and MT patients, bivalirudin plus eptifibatide was associated with markedly lower PR at all times (5- and 20-microM adenosine diphosphate-induced, and 15- and 25-microM thrombin receptor activator peptide-induced aggregation; p < 0.001 for all) and reduced mean TIP-FCS (p < 0.05). Patients who had a periprocedural infarction had higher mean 18-h PR (p < 0.0001) and TIP-FCS (p = 0.002).. For elective stenting, the addition of eptifibatide to bivalirudin lowered PR to multiple agonists and the tensile strength of the TIP-FCS, 2 measurements strongly associated with periprocedural myonecrosis. Future studies of PR and TIP-FCS for elective stenting may facilitate personalized antiplatelet therapy and enhance the selection of patients for glycoprotein IIb/IIIa blockade. (Peri-Procedural Myocardial Infarction, Platelet Reactivity, Thrombin Generation, and Clot Strength: Differential Effects of Eptifibatide + Bivalirudin Versus Bivalirudin [CLEAR PLATELETS-2]; NCT00370045.

Topics: Adenosine Diphosphate; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Blood Coagulation; Blood Platelets; Clopidogrel; Collagen; Drug Therapy, Combination; Eptifibatide; Female; Hemorheology; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptides; Platelet Aggregation; Platelet Aggregation Inhibitors; Receptors, Thrombin; Recombinant Proteins; Stents; Thrombelastography; Ticlopidine

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

The lack of a specific counteragent to bivalirudin may complicate the management of patients with coronary artery (CA) perforation during percutaneous coronary intervention (PCI).. Assess outcomes of patients with CA perforation from three PCI trials comparing intravenous bivalirudin with provisional glycoprotein (GP) IIb/IIIa inhibition versus unfractionated heparin (UFH) plus GP IIb/IIIa.. A pooled analysis of patients treated with PCI in three randomized trials including REPLACE-2, ACUITY, and HORIZONS-AMI.. Among a total of 12,921 patients, CA perforation occurred in 35 patients (0.27%). By multivariable analysis, baseline creatinine clearance was the only independent predictor of CA perforation (per 10 mL/min decrease, odds ratio [95% confidence interval]= 1.28 [1.11, 1.47], P = 0.0007). At 30 days, patients with versus without CA perforation had significantly (all P values < or =0.001) higher rates of 30-day mortality (11.4% vs. 1.0%), myocardial infarction (MI) [Q wave: 22.9% vs. 5.7%; non-Q wave: 17.1% vs. 4.9%], target vessel revascularization (TVR) [20.1% vs. 1.8%], and composite end-point of death/MI/TVR (31.4% vs. 7.8%). Patients assigned to bivalirudin versus UFH plus a GP IIb/IIIa inhibitor had nonsignificantly lower rates of death (0% vs. 18.8%, P = 0.08), similar rates of MI (26.7% vs. 25.0%, P = 0.92), significantly lower rates of TVR (6.7% vs. 37.5%, P = 0.04), and similar rates of the composite end-point of death/MI/TVR (35.5% vs. 26.7%, P = 0.54).. In three PCI trials, treatment of patients experiencing CA perforation with adjunctive antithrombotic therapy of bivalirudin monotherapy was not associated with worse outcomes compared to treatment with UFH plus GP IIb/IIIa inhibitors.

Topics: Aged; Anticoagulants; Chemotherapy, Adjuvant; Coronary Vessels; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Survival Rate; Treatment Outcome; Wounds, Penetrating

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

We assessed the incidence, predictors, and outcomes of gastrointestinal bleeding (GIB) in patients with acute coronary syndromes (ACS).. GIB is a potential hemorrhagic complication in patients with ACS treated with antithrombotic and/or antiplatelet medications. The clinical outcomes associated with GIB in this setting have not been systematically studied.. In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients with moderate- and high-risk ACS, enrolled at 450 centers in 17 countries between August 2003 and December 2005, were randomized to the open-label use of 1 of 3 antithrombin regimens (heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin monotherapy).. GIB within 30 days occurred in 178 patients (1.3%). Older age, baseline anemia, longer duration of study drug administration before angiogram, smoking, ST-segment deviation>or=1 mm, and diabetes were identified as independent predictors of GIB. On multivariable analysis, GIB was strongly associated with 30-day all-cause mortality (hazard ratio [HR]: 4.87 [interquartile range (IQR) 2.61 to 9.08], p<0.0001), cardiac mortality (HR: 5.35 [IQR 2.71 to 10.59], p<0.0001), and composite ischemia (HR: 1.94 [IQR 1.14 to 3.30], p=0.014), as well as with 1-year all-cause mortality (HR: 3.97 [IQR 2.64 to 5.99], p<0.0001), cardiac mortality (HR: 3.77 [IQR 2.14 to 6.63], p<0.0001), myocardial infarction (HR: 1.74 [IQR 1.01 to 3.02], p=0.047), and composite ischemia (HR: 1.90 [IQR 1.37 to 2.64], p=0.0001). Patients who experienced GIB had significantly higher rates of stent thrombosis compared with patients without GIB (5.8% vs. 2.4%, p=0.009).. GIB is a serious condition in the scenario of ACS and is independently associated with mortality and ischemic complications.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Coronary Artery Bypass; Female; Gastrointestinal Hemorrhage; Heparin; Hirudins; Humans; Incidence; Ischemia; Length of Stay; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Sex Factors; Stents; Thrombosis; Ticlopidine

Our aim was to determine whether a 600-mg loading dose of clopidogrel compared with 300 mg results in improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).. A 600-mg loading dose of clopidogrel compared with 300 mg provides more rapid and potent inhibition of platelet activation.. In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, 3,602 patients with STEMI undergoing primary PCI were randomized to bivalirudin (n = 1,800) or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (n = 1,802). Randomization was stratified by thienopyridine loading dose, which was determined before random assignment.. Patients in the 600-mg (n = 2,158) compared with the 300-mg (n = 1,153) clopidogrel loading dose group had significantly lower 30-day unadjusted rates of mortality (1.9% vs. 3.1%, p = 0.03), reinfarction (1.3% vs. 2.3%, p = 0.02), and definite or probable stent thrombosis (1.7% vs. 2.8%, p = 0.04), without higher bleeding rates. Compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin monotherapy resulted in similar reductions in net adverse cardiac event rates within the 300-mg (15.2% vs. 12.3%) and 600-mg (10.4% vs. 7.3%) clopidogrel loading dose subgroups (p(interaction) = 0.41). By multivariable analysis, a 600-mg clopidogrel loading dose was an independent predictor of lower rates of 30-day major adverse cardiac events (hazard ratio: 0.72 [95% confidence interval: 0.53 to 0.98], p = 0.04).. In patients with STEMI undergoing primary PCI with contemporary anticoagulation regimens, a 600-mg loading dose of clopidogrel may safely reduce 30-day ischemic adverse event rates compared with a 300-mg loading dose. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon; Anticoagulants; Clopidogrel; Confidence Intervals; Female; Hirudins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Proportional Hazards Models; Recombinant Proteins; Ticlopidine; Treatment Outcome

Modern antithrombotic strategies for patients undergoing percutaneous coronary interventions (PCIs) must take into account the risk of ischemic and hemorrhagic complications. Bivalirudin decreases the risk of hemorrhagic complications after PCI; however, concerns have been raised about its efficacy in preventing ischemic complications. We evaluated the effectiveness of a prolonged intra- and postprocedural bivalirudin infusion versus a standard regimen in preventing PCI-related myocardial damage. One hundred seventy-eight consecutive patients with stable or unstable angina and complex coronary anatomy were enrolled in this single-center, randomized, single-blinded study. Patients were randomized to bolus plus bivalirudin infusion during PCI (n = 90) or bolus plus bivalirudin infusion during and after PCI (4 hours, n = 88). The primary end point was incidence of periprocedural myocardial damage (creatine kinase-MB increase >or=3 times upper limit of normal). Secondary end points were 30-day and 6-month major adverse cardiovascular events (death, new Q-wave myocardial infarction, target vessel revascularization) and in-hospital bleeding (major/minor). The 2 groups did not differ significantly in baseline and procedural characteristics. The primary end point of the study was significantly less frequent in the prolonged infusion group (6.8% vs 16.7%, p = 0.041). No significant differences for secondary end points were observed. In conclusion, in patients undergoing complex PCI, a prolonged bivalirudin infusion after PCI compared to an intraprocedural-only regimen significantly decreased the incidence of periprocedural myocardial damage.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Delayed-Action Preparations; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Hirudins; Humans; Incidence; Infusions, Intravenous; Italy; Male; Myocardial Infarction; Peptide Fragments; Prospective Studies; Recombinant Proteins; Single-Blind Method; 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

Advances in coronary angioplasty and adjunct pharmacology have improved patient outcomes after primary percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI). However, several areas for improvement remain. Hemorrhagic complications, which are common in patients receiving intense anticoagulant and antiplatelet agents during primary PCI to suppress ischemia, have been strongly associated with early and late mortality. Moreover, restenosis after bare-metal stents (BMSs) frequently results in symptom recurrence and the need for repeat rehospitalization and revascularization procedures. Newer pharmacologic agents and drug-eluting stents may address both of these issues.. In the HORIZONS-AMI trial, 3,602 patients with AMI undergoing primary PCI were prospectively randomized to unfractionated heparin plus routine use of glycoprotein (GP) IIb/IIIa inhibitors versus the direct thrombin inhibitor bivalirudin plus provisional use of GP IIb/IIIa inhibitors reserved for predefined thrombotic complications. In a second randomization, 3,011 eligible patients were randomly assigned to either a polymer-based paclitaxel-eluting stent or to an otherwise identical BMS. The study was powered for the assessment of sequential safety and efficacy end points for each specific randomization, with clinical end points assessed at 30 days, 1 year, and then annually for 5 years.. The ongoing HORIZONS-AMI trial will determine whether bivalirudin monotherapy reduces bleeding complications and improves overall event-free survival compared with unfractionated heparin plus the routine use of GP IIb/IIIa inhibitors in patients undergoing primary PCI for AMI. Furthermore, this study will determine whether paclitaxel-eluting stents safely reduce rates of ischemic target lesion revascularization compared with BMSs in the setting of primary PCI.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Combined Modality Therapy; Coronary Angiography; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Eluting Stents; Follow-Up Studies; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Probability; Prospective Studies; Recombinant Proteins; Reference Values; Research Design; Risk Assessment; Stents; Survival Rate; Thrombosis; Time Factors

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

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

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

The aim was to compare 2-year outcomes with the routine use of drug-eluting stents (DES) (>75% "off-label") with a comparable group treated with bare-metal stents (BMS).. Safety concerns >1 year from implantation have been raised about DES used "off-label." There are limited data comparing DES and BMS in "off-label" patients.. Clinical outcomes (nonfatal myocardial infarction [MI], all-cause mortality) were assessed in 1,164 consecutive patients who received BMS in the year before introduction of DES at Wake Forest University Baptist Medical Center and 1,285 consecutive patients who received DES after it became our routine choice. "On-label" stent use was defined as treatment for a single de novo lesion <30 mm, without recent MI or other major illnesses.. At 2 years, the hazard ratio for DES compared with BMS for nonfatal MI or death was 0.77 (95% confidence interval [CI] 0.62 to 0.95), for all-cause mortality 0.71 (0.54 to 0.92), and stent thrombosis (ST) 0.97 (0.49 to 1.91). "On-label" stent procedures were associated with lower risk of MI, death, and ST than "off-label" stent procedures. For "off-label" stent procedures, the hazard ratio for DES compared with BMS for nonfatal MI or death was 0.78 (95% CI 0.62 to 0.98), all-cause mortality 0.72 (0.54 to 0.94), and ST 0.91 (0.46 to 1.80). The hazard of nonfatal MI or death was similar or lower for DES than BMS in high-risk subgroups, including renal failure and recent MI.. The routine clinical use of drug-eluting stents for "off-label" indications was associated with lower nonfatal MI and death at 2 years than in a comparable group of patients treated with BMS.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Blood Vessel Prosthesis Implantation; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Heparin; Hirudins; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Peptide Fragments; Proportional Hazards Models; Recombinant Proteins; Risk Factors; Secondary Prevention; Sirolimus; Treatment Outcome

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

Patients who suffer re-infarction during initial hospitalization for ST-elevation myocardial infarction (STEMI) have decreased survival compared to patients without re-infarction, so treatment of re-infarction may influence survival.. To determine whether the utilization of reperfusion therapies varied within 12 h of re-infarction and was associated with 30-day mortality, we studied 552 patients with re-infarction of 17,073 patients with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western Countries, Asia, and Latin America). Patients presenting within 6 h of symptom-onset were randomized to receive either bivalirudin or unfractionated heparin intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6% of bivalirudin and heparin treated patients, respectively (P = 0.004), but treatment assignment did not influence mortality after re-infarction. Patients with re-infarction had a higher 30-day mortality than those without re-infarction (24 vs. 10%; P < 0.001 by Cox model). Within 12 h of re-infarction, fibrinolytic therapy was administered to 12.0 and 8.2% underwent percutaneous coronary intervention (PCI); these two treatments were more frequently utilized in patients from Western countries (n = 112), compared to patients from other countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P < 0.001). Mortality was 15% in patients receiving reperfusion therapy for re-infarction and 27% for those with conservative management, hazard ratio (HR) 0.53 (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included adjustment for clinical variables and randomized treatment assignment, 30-day mortality after re-infarction varied by region (highest Latin America 29%, lowest Western countries 15%; P = 0.01). Other independent prognostic factors included age, time from randomization to re-infarction, and Killip class at randomization. The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0.02] in analyses which excluded deaths within 12 h.. Treatment of re-infarction with reperfusion therapies was markedly under-utilized, especially in non-western countries. PCI for re-infarction, in particular, was associated with a lower 30-day mortality, which may reflect both patient selection and effects of treatment.

Topics: Aged; Angioplasty, Balloon, Coronary; Electrocardiography; Female; Fibrinolytic Agents; Heart Conduction System; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Recurrence; Time Factors; Treatment Outcome

The relation across anemia, hemorrhagic complications, and mortality associated with percutaneous coronary intervention (PCI) is unclear. We reviewed the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 Trial, which compared bivalirudin plus provisional glycoprotein IIb/IIIa blockade with heparin plus planned glycoprotein IIb/IIIa blockade in patients undergoing urgent or elective PCI. Of the 6,010 patients randomized in REPLACE-2, 1,371 (23%) were anemic. Major bleeding was more common in anemic than in nonanemic patients (4.9% vs 2.8%, p = 0.0001). In anemic patients, treatment with bivalirudin (n = 678) resulted in a lower risk of major bleeding versus heparin plus glycoprotein IIb/IIIa blockade (n = 693, 3.5% vs 6.2%, p = 0.0221). Mortality was higher in anemic patients than in nonanemic patients at 30 days (0.9% vs 0.2%, p <0.0001), 6 months (2.6% vs 0.7%, p <0.0001), and 1 year (4.3% vs 1.5%, p <0.0001). There were no differences between anemic and nonanemic patients with regard to ischemic complications at 30 days. Although anemic patients had higher mortality rates, proportions of cardiovascular and noncardiovascular mortalities were equal in anemic and nonanemic patients. In conclusion, anemic patients undergoing PCI have an increased risk of mortality and major bleeding, but not of ischemic events, and the use of bivalirudin with provisional glycoprotein IIb/IIIa blockade decreases the risk of hemorrhagic complications compared with heparin plus planned glycoprotein IIb/IIIa blockade.

Topics: Aged; Anemia; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Cause of Death; Double-Blind Method; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Hemorrhage; Predictive Value of Tests; Proportional Hazards Models; Recombinant Proteins; Research Design; Risk Factors; Treatment Outcome

The present study evaluated the combined use of unfractionated heparin (UFH) and bivalirudin during ad hoc transradial interventional procedures.. As a result of its proven efficacy in recent clinical trials, the direct thrombin inhibitor bivalirudin is now increasingly utilized as the anticoagulant of choice for coronary interventions. However, it is currently not packaged for diagnostic procedures. Patients undergoing ad hoc transradial procedures thus need unfractionated heparin during the diagnostic catheterization to protect against radial occlusion. It is unclear how the transition to bivalirudin should be undertaken if a subsequent intervention were performed.. A total of 117 patients underwent ad hoc transradial procedures. Fifty-one patients underwent diagnostic catheterizations receiving only 5,000 Units of UFH in divided doses: (1) Group 1H (n = 26), 2,500 U after sheath insertion and 2,500 U at conclusion; (2) Group 2H (n = 25), 1,000 U followed by 4,000 U. Sixty-six patients subsequently underwent interventions as part of the same procedure and received standard bivalirudin (B) dosing in addition to the initial UHF dose: Group 1B (n = 40), 2,500 Units of UFH plus B; Group 2B (n = 26), 1,000 Units of UFH plus B. The primary endpoint was postprocedure radial occlusion; secondary endpoints were any major adverse cardiac event (MACE) and any bleeding complication.. One patient (1%) had postprocedure radial occlusion, but this recanalized at 1 month. There were no deaths, and urgent target lesion revascularization was not required. Non-Q wave myocardial infarction occurred in 7.5%, all in Group 1B. No bleeding complications occurred.. The administration of bivalirudin after a reduced heparin dose in patients undergoing ad hoc transradial interventional procedures was not associated with adverse events in this small pilot study.

Topics: Aged; Anticoagulants; Arterial Occlusive Diseases; Cardiac Catheterization; Chemotherapy, Adjuvant; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Incidence; Inpatients; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Pilot Projects; Prospective Studies; Radial Artery; Recombinant Proteins; Whole Blood Coagulation Time

Drug-eluting stents (DESs) deliver biphasic (early and late) elution of anti-inflammatory compounds. We therefore hypothesized that DESs would be associated with early reductions in inflammatory biomarker release after percutaneous coronary intervention (PCI). A total of 741 patients with non-ST-elevation acute coronary syndrome underwent PCI in the Randomized Trial to Evaluate the Relative PROTECTion against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia among Anti-Platelet and Anti-Thrombotic Agents (PROTECT) Thrombolysis In Myocardial Infarction 30 study of eptifibatide and reduced-dose antithrombin compared with bivalirudin. Serial biomarkers C-reactive protein, troponin, creatine kinase-MB, soluble CD40 ligand, interleukin-6, prothrombin fragment F1.2, and RANTES (regulated on activation, normal T-cell expressed and secreted) were assessed through 24 hours after PCI. DES use was at the investigator's discretion. Patients treated with DESs (n = 665) versus bare metal stents (n = 139) were more likely to have patent arteries before PCI (92.0% vs 86.6%, p = 0.04), Thrombolysis In Myocardial Infarction myocardial perfusion grade 3 (57.9% vs 47.7%, p = 0.033), and the left anterior descending artery as the culprit artery (38.5% vs 18.3%, p <0.001). The increase in C-reactive protein and troponin was lower among patients undergoing DES implantation (median 2.1 vs 3.5 mg/L for C-reactive protein, median 0.11 vs 0.41 ng/ml for troponin), even after adjustment for randomized treatment, clopidogrel before treatment, diabetes mellitus status, epicardial patency, left anterior descending artery location, and myocardial perfusion (p = 0.036 and p = 0.039, respectively). Interleukin-6 was lower with DESs on univariate analysis but not multivariate analysis. Creatine kinase-MB, soluble sCD40 ligand, prothrombin fragment F1.2, and RANTES did not differ by DES use. In conclusion, patients undergoing DES implantation achieved more reductions in periprocedural markers of inflammation and necrosis than patients receiving bare metal stents among those with non-ST-elevation acute coronary syndrome.

Topics: Angioplasty, Balloon, Coronary; Antithrombin III; Biomarkers; C-Reactive Protein; CD40 Ligand; Chemokine CCL5; Creatine Kinase, MB Form; Drug Delivery Systems; Eptifibatide; Female; Heparin; Hirudins; Humans; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptides; Prospective Studies; Prothrombin; Recombinant Proteins; Stents; Treatment Outcome; Troponin

Postmortem and angiographic studies have demonstrated that thrombosis is the primary cause of coronary artery occlusion in smokers. Further, smokers have high levels of fibrinogen, increased platelet aggregation, and more platelet-dependent thrombin generation than do nonsmokers, suggesting that glycoprotein (GP) IIb/IIIa inhibitor use during percutaneous coronary intervention (PCI) may be especially useful among smokers. We evaluated a subpopulation of active smokers in the REPLACE-2 trial to assess the effect of treating smokers with bivalirudin and provisional GP IIb/IIIa blockade compared with heparin and planned GP IIb/IIIa blockade. The REPLACE-2 trial enrolled 1,558 smokers and 4,305 nonsmokers. Smokers who were treated with bivalirudin had an absolute 3.2% increase in the composite end point of death and myocardial infarction at 48 hours compared with smokers who were treated with heparin and GP IIb/IIIa inhibitors (7.7% vs 4.5%, p=0.008, interaction p=0.016). This difference was ameliorated when GP IIb/IIIa inhibitors were used consistently in a previous trial that compared bivalirudin with heparin during PCI (4.6% vs 6.7%, p=0.322). In conclusion, these results suggest that smokers may derive particular benefit with GP IIb/IIIa inhibitors for decreasing myocardial infarction and death after PCI. These findings require further validation from other large, randomized trials.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Disease; Double-Blind Method; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Smoking; Survival Analysis

The goal of this study was to evaluate glycoprotein IIb/IIIa inhibition with eptifibatide when administered with indirect thrombin inhibition as compared with monotherapy with direct thrombin inhibition with bivalirudin among patients with non-ST-segment elevation acute coronary syndromes (ACS).. The optimal combination of antiplatelet and antithrombin regimens that maximizes efficacy and minimizes bleeding among patients with non-ST-segment elevation ACS undergoing percutaneous coronary intervention (PCI) is unclear.. A total of 857 patients with non-ST-segment elevation ACS were assigned randomly to eptifibatide + reduced dose unfractionated heparin (n = 298), eptifibatide + reduced-dose enoxaparin (n = 275), or bivalirudin monotherapy (n = 284).. Among angiographically evaluable patients (n = 754), the primary end point of post-PCI coronary flow reserve was significantly greater with bivalirudin (1.43 vs. 1.33 for pooled eptifibatide arms, p = 0.036). Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade more often was normal with eptifibatide treatment compared with bivalirudin (57.9% vs. 50.9%, p = 0.048). The duration of ischemia on continuous Holter monitoring after PCI was significantly longer among patients treated with bivalirudin (169 vs. 36 min, p = 0.013). There was no excess of TIMI major bleeding among patients treated with eptifibatide compared with bivalirudin (0.7%, n = 4 vs. 0%, p = NS), but TIMI minor bleeding was increased (2.5% vs. 0.4%, p = 0.027) as was transfusion (4.4% to 0.4%, p < 0.001).. Among moderate- to high-risk patients with ACS undergoing PCI, coronary flow reserve was greater with bivalirudin than eptifibatide. Eptifibatide improved myocardial perfusion and reduced the duration of post-PCI ischemia but was associated with higher minor bleeding and transfusion rates. Ischemic events and biomarkers for myonecrosis, inflammation, and thrombin generation did not differ between agents.

Topics: Acute Disease; Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Drug Therapy, Combination; Enoxaparin; Eptifibatide; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Syndrome

The presence of pathological Q waves in the infarct leads on the surface electrocardiogram in an ST-elevation acute myocardial infarction indicates myocardial necrosis. Clinically it might be difficult to ascertain the onset of acute myocardial infarction. Our aim was to assess whether the presence or absence of Q waves at presentation could be used as an indicator of the duration of acute myocardial infarction and predict mortality.. 15,222 patients with ST-elevation acute myocardial infarction and normal intraventricular conduction were randomly assigned streptokinase and aspirin plus bivalirudin or unfractionated heparin in the HERO-2 trial; randomisation did not alter 30-day mortality. 10,244 patients (67%) had Q waves in the infarct territory at the time of randomisation, and 4978 (33%) did not. The primary endpoint was 30-day mortality.. There were more deaths at 30 days in patients with initial Q waves than in those without (1044 [10%] vs 344 [7%], p<0.0001). These findings were similar in patients with a first acute myocardial infarction and when stratified by time to randomisation (0-2, >2-4, >4 h) and by acute myocardial infarction location (anterior or inferior). Both the presence of initial Q waves and time to randomisation were positive univariate predictors, but only the presence of initial Q waves independently predicted 30-day mortality on multivariate analysis (adjusted OR 1.44, 95% CI 1.25-1.65 with clinical indices, and 1.31, 1.12-1.54 with clinical plus ST indices included as predictors).. The presence of Q waves in the infarct leads at presentation of ST-elevation acute myocardial infarction independently predicts higher 30-day mortality in patients treated with fibrinolytic therapy. Therefore, a more aggressive approach to reperfusion might be warranted in these patients.

Topics: Aged; Anticoagulants; Aspirin; Drug Therapy, Combination; Electrocardiography; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Predictive Value of Tests; Recombinant Proteins; Streptokinase; Thrombolytic Therapy

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

Patients with acute coronary syndromes (ACS; unstable angina and non-ST-segment elevation myocardial infarction) are at significant risk for death and myocardial infarction. Early angiography followed by revascularization is considered the treatment of choice for moderate- to high-risk patients with ACS. However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors, and thienopyridines, the rate of adverse ischemic events still remains unacceptably high, and the intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty and surgical revascularization procedures elicit a high rate of bleeding complications. Pilot trials suggest that the thrombin-specific anticoagulant bivalirudin may improve clinical outcomes in ACS.. In the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial, 13,800 patients with moderate- to high-risk ACS are being prospectively randomly assigned at up to 600 centers to unfractionated heparin or enoxaparin + IIb/IIIa inhibition, versus bivalirudin + IIb/IIIa inhibition, versus bivalirudin + provisional IIb/IIIa inhibition. All patients undergo cardiac catheterization within 72 hours, followed by percutaneous or surgical revascularization when appropriate. In a second random assignment, patients assigned to receive IIb/IIIa inhibitors are subrandomized to upstream drug initiation, versus IIb/IIIa inhibitor administration during angioplasty only. The primary study end point is the composite of death, myocardial infarction, unplanned revascularization for ischemia, and major bleeding at 30 days. Clinical follow-up will continue for 1 year.. The ACUITY trial is the largest study yet performed in patients with ACS undergoing an invasive strategy. In addition to evaluating the utility of bivalirudin in ACS, this study will also provide important guidance regarding the necessity for and timing of IIb/IIIa inhibitor administration.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Cardiac Catheterization; Combined Modality Therapy; Coronary Artery Bypass; Enoxaparin; Heparin; Hirudins; Humans; Multicenter Studies as Topic; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design

Topics: Adult; Anesthesia, Intravenous; Anticoagulants; Blood Coagulation; Cardiopulmonary Bypass; Endopeptidases; Female; Fibrinolytic Agents; Hirudins; Humans; In Vitro Techniques; Monitoring, Intraoperative; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Snake Venoms; Time Factors

The presence of Q waves at presentation with a first acute myocardial infarction reflects a more advanced stage of the infarction process. When infarct-related artery patency (Thrombolysis in Myocardial Infarction 2 or 3 flow) is restored, resolution of ST segment elevation indicating successful myocyte reperfusion may differ according to how far the infarction process has progressed.. In 144 patients with a first acute myocardial infarction treated with streptokinase in the first Hirulog Early Reperfusion Occlusion trial, information was obtained from continuous ST segment monitoring, the presenting electrocardiogram and early angiography performed at a median time of 99 min after the commencement of streptokinase (interquartile range 89-108 min). We determined how many patients had 50% ST recovery within 120 min and in how many cases it was sustained over 4h. In the 109 patients with patent infarct-related arteries, 50% ST recovery occurred in 95% of patients without vs 80% of those with initial Q waves (P=0.03), and sustained ST recovery occurred in 67% of patients without vs 47% of those with initial Q waves (P=0.03). On multivariate analysis including the time from symptom onset to streptokinase therapy, the presence of Q waves at presentation was the only predictor of failure to achieve 50% ST recovery (odds ratio 5.08, 95% confidence interval 1.29-20.01, P=0.02). TIMI 2 flow, as opposed to TIMI 3 flow, was the only predictor of failure to achieve stable ST recovery (odds ratio 2.63, 95% confidence interval 1.15-5.88,P =0.02).. The presence of initial Q waves predicts slower and less complete ST recovery, reflecting reduced myocyte reperfusion, even in those with early infarct artery patency. These patients may be targeted for new therapeutic strategies to improve microvascular reperfusion.

Topics: Acute Disease; Anticoagulants; Aspirin; Coronary Angiography; Coronary Circulation; Double-Blind Method; Electrocardiography; Endpoint Determination; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Streptokinase; Thrombolytic Therapy; Vascular Patency

A Bayesian methodology is developed to investigate the homogeneity of the treatment effects in a multi-centre clinical trial with an ordinal response. A hierarchical model is formulated for the ordinal response, and the marginal posterior distributions of the covariates, overall treatment and the centre effects are calculated using the Gibbs sampler. The methodology is applied to data arising from a multi-centre clinical trial of therapies for acute myocardial infarction. In this trial, the overall results show that the treatment is effective. However, there appears to be substantial differences in both the baseline risk and treatment effect across centres. Thus, the observed treatment effects may not be generalized to a broader patient population, and exploratory analyses to ascertain reasons for the treatment-by-centre interaction and its possible effect on the study conclusions would be useful.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Bayes Theorem; Clinical Trials, Phase I as Topic; Coronary Angiography; Female; Fibrinolytic Agents; Hirudins; Humans; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Regression Analysis; Streptokinase; 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

The combination of fibrinolytic therapy and heparin for acute myocardial infarction fails to achieve reperfusion in 40-70% of patients, and early reocclusion occurs in a substantial number. We did a randomised, open-label trial to compare the thrombin-specific anticoagulant, bivalirudin, with heparin in patients undergoing fibrinolysis with streptokinase for acute myocardial infarction.. 17073 patients with acute ST-elevation myocardial infarction were randomly assigned an intravenous bolus and 48-h infusion of either bivalirudin (n=8516) or heparin (n=8557), together with a standard 1.5 million unit dose of streptokinase given directly after the antithrombotic bolus. The primary endpoint was 30-day mortality. Secondary endpoints included reinfarction within 96 h and bleeding. Strokes and reinfarctions were adjudicated by independent committees who were unaware of treatment allocation. Analysis was by intention to treat.. By 30 days, 919 patients (10.8%) in the bivalirudin group and 931 (10.9%) in the heparin group had died (odds ratio 0.99 [95% CI 0.90-1.09], p=0.85). The mortality rates adjusted for baseline risk factors were 10.5% for bivalirudin and 10.9% for heparin (0.96 [0.86-1.07], p=0.46). There were significantly fewer reinfarctions within 96 h in the bivalirudin group than in the heparin group (0.70 [0.56-0.87], p=0.001). Severe bleeding occurred in 58 patients (0.7%) in the bivalirudin group versus 40 patients (0.5%) in the heparin group (p=0.07), and intracerebral bleeding occurred in 47 (0.6%) versus 32 (0.4%), respectively (p=0.09). The rates of moderate and mild bleeding were significantly higher in the bivalirudin group than the heparin group (1.32 [1.00-1.74], p=0.05; and 1.47 [1.34-1.62], p<0.0001; respectively). Transfusions were given to 118 patients (1.4%) in the bivalirudin group versus 95 patients (1.1%) in the heparin group (1.25 [0.95-1.64], p=0.11).. Bivalirudin did not reduce mortality compared with unfractionated heparin, but did reduce the rate of adjudicated reinfarction within 96 h by 30%. Small absolute increases were seen in mild and moderate bleeding in patients given bivalirudin. Bivalirudin is a new anticoagulant treatment option in patients with acute myocardial infarction treated with streptokinase.

Topics: Aged; Anticoagulants; Antithrombins; Endpoint Determination; Female; Hemodynamics; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Risk Factors

The objective of this study was to identify predictors of major adverse cardiac events after successful coronary angioplasty.. The acute complications of angioplasty are related to baseline clinical and angiographic variables, and early complications adversely affect long-term outcome. However, the predictors of enduring success after uncomplicated angioplasty are less well defined.. Of 4,098 patients undergoing angioplasty in the Hirulog Angioplasty Study, 3,899 (95%) had a successful procedure without in-hospital death, emergent bypass surgery or clinical evidence of myocardial infarction. Baseline and procedural variables for these 3,899 patients were examined.. Major adverse cardiac events occurred in 22% of the patients with initially successful procedures at 6 months: death in 1%, myocardial infarction in 2% and repeat revascularization in 21%. Univariable predictors of increased events included successful salvage from abrupt vessel closure (p < 0.001), emergency stenting (p < 0.001), multilesion angioplasty (p < 0.001), diabetes (p=0.02), target lesion in the left anterior descending artery (p=0.02), unstable angina (p=0.03) and smaller final luminal diameter (p=0.04). There was a trend toward increased events among patients with prior angioplasty (p=0.08), but asymptomatic elevation of the creatine kinase was not predictive (p=0.5). In a multivariable model, abrupt vessel closure was the strongest independent predictor of major adverse cardiac events at 6 months (p < 0.001; odds ratio [95% confidence interval]=3.6 [2.5 to 5.1]), while multivessel angioplasty, target lesion in the left anterior descending artery and diabetes also remained independent predictors (all p < or = 0.02).. This analysis suggests that "uncomplicated" abrupt vessel closure is a powerful predictor of adverse clinical outcome following successful angioplasty. Improved techniques to reduce abrupt closure during angioplasty are thus urgently needed, and patients who experience "uncomplicated" closure require closer surveillance during follow-up.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Double-Blind Method; Female; Follow-Up Studies; Heparin; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Recurrence; Stents; Survival Rate

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Follow-Up Studies; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Recurrence; Stents; Survival Rate; Treatment Outcome

The presenting electrocardiogram may contain information indicating the probability of successful reperfusion. The relation between 3 parameters in the presenting electrocardiogram (pathologic Q waves, T-wave inversion, and the slope of ST elevation) and Thrombolysis in Myocardial Infarction trial (TIMI) grade 3 flow in the infarct-related artery was assessed angiographically 90 minutes after beginning streptokinase in 362 patients. TIMI grade 3 flow was more common in patients without Q waves (55%) than in those with Q waves (35%; p <0.001), and more common in patients without T-wave inversion (50%) than in those with T-wave inversion (30%; p <0.002). There was no relation between the slope of the ST segment or the magnitude of its deviation and the achievement of TIMI grade 3 flow. Only 20% of the 59 patients with both Q waves and T-wave inversion had TIMI grade 3 flow, compared with 50% of the remaining patients (p <0.0001). Among patients treated within 3 hours, TIMI grade 3 flow was seen in 68% of those without versus 44% of those with Q waves (p <0.01), and in 62% of those without versus 43% of those with T-wave inversion (p = 0.06). Among patients treated after 3 hours, TIMI grade 3 flow was seen in 38% of those without versus 30% of those with Q waves (p = NS), and in 38% of those without versus 23% of those with T-wave inversion (p <0.05). On multivariate analysis, the absence of Q waves, the time from the onset of chest pain to treatment, and age were independent predictors of TIMI grade 3 flow. Pathologic Q waves in the presenting electrocardiogram provide valuable information as to the probability of achieving successful reperfusion following administration of streptokinase, and may be helpful for triage of patients to alternative reperfusion strategies, including percutaneous revascularization.

Topics: Anticoagulants; Cohort Studies; Coronary Angiography; Electrocardiography; Female; Fibrinolytic Agents; Hirudin Therapy; Hirudins; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments; Predictive Value of Tests; Recombinant Proteins; Streptokinase

Unlike unfractionated heparin, direct thrombin inhibitors such as hirudin and Hirulog inhibit clot-bound as well as fluid-phase thrombin, escape neutralisation by platelet secretion products, do not require monitoring, and are unassociated with immune thrombocytopenia. They have been shown to have modest advantages over heparin when given after thrombolytic therapy, reducing reinfarction by 14%. In the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO 2b) trial, patients treated with streptokinase and adjunctive hirudin had a reduction in death or myocardial infarction of 40% at 30 days (8.6% with hirudin versus 14.4% with heparin, p = 0.004). In the Hirulog Early Reperfusion/Occlusion (HERO 1) trial, 48% of patients who received Hirulog as adjunctive therapy with streptokinase had Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow in the infarct-related artery, compared with 35% of patients who received heparin with streptokinase (p < 0.05). The HERO 2 study, involving 17,000 patients, will test the hypothesis that Hirulog and aspirin given before streptokinase will reduce mortality compared with aspirin plus heparin. Early administration of direct thrombin inhibitors may potentially improve the outcome of patients treated with thrombolytic therapy.

Topics: Aged; Antithrombins; Aspirin; Female; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Streptokinase; Thrombolytic Therapy

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

Worldwide, streptokinase continues to be used widely in the treatment of myocardial infarction because it is inexpensive and causes fewer intracranial hemorrhages than other thrombolytic regimens. However, in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-I) trial, the 90-minute angiographic Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow rate with streptokinase was 43% lower than that with accelerated tissue plasminogen activator, and there was a higher incidence of death or disabling stroke with streptokinase (7.8% vs 6.9%, p <0.01). In the first Hirulog and Early Reperfusion/Occlusion (HERO-1) trial, 48% of patients given the direct thrombin inhibitor bivalirudin (formerly Hirulog, The Medicines Company) after streptokinase had TIMI 3 patency at 90 minutes, compared with 35% of patients given intravenous heparin (p <0.05). Other angiographic and clinical studies and animal research have shown that early infarct artery blood flow may be increased markedly if a direct thrombin inhibitor is administered before the thrombolytic agent. In the HERO-2 trial, 17,000 patients presenting within 6 hours after the onset of acute myocardial infarction will be given aspirin and randomized to receive either intravenous heparin or bivalirudin before streptokinase is administered. The primary endpoint will be 30-day mortality, and secondary endpoints will include death or myocardial infarction within 30 days, and death or nonfatal disabling stroke. If the thrombin hypothesis is supported by improved clinical outcomes with bivalirudin in the HERO-2 trial, large-scale clinical trials will be needed to evaluate the administration of direct thrombin inhibitors before other thrombolytic regimens.

Topics: Antithrombins; Cerebral Hemorrhage; Cerebrovascular Disorders; Coronary Angiography; Drug Therapy, Combination; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Research Design; Streptokinase

Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates.. Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg x kg(-1) x h(-1) for 12 hours then 0.125 mg x kg(-1) x h(-1)), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg x kg(-1) x h(-1) for 12 hours then 0.25 mg x kg(-1) x h(-1)). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CI, 40% to 57%) with high-dose hirulog (heparin versus hirulog, P=.023; heparin versus high-dose hirulog, P=.03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog patients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog, P<.01).. Hirulog was more effective than heparin in producing early patency in patients treated with aspirin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.

Topics: Analysis of Variance; Antithrombins; Aspirin; Cardiac Catheterization; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Recurrence; Streptokinase; Thrombolytic Therapy

Direct thrombin inhibitors are a new class of drugs that may offer a more effective and potentially simpler alternative to heparin. Hirulog is a synthetic peptide based on the leech-derived compound hirudin and, like hirudin, is a highly specific, direct inhibitor of free and clot-bound thrombin.. TIMI 7 was a randomized, double-blind study of Hirulog, given with 325 mg/d aspirin to 410 patients with unstable angina. Patients received a constant infusion of Hirulog for 72 hours at one of four doses: 0.02 (n = 160), 0.25 (n = 81), 0.5 (n = 88), and 1.0 (n = 81) mg.kg-1.h-1. The primary efficacy end point was "unsatisfactory outcome," defined as death, nonfatal myocardial infarction (MI), rapid clinical deterioration, or recurrent ischemic pain at rest with ECG changes by 72 hours. Unsatisfactory outcome was not different among the four dose groups: 8.1%, 6.2%, 11.4%, and 6.2% (P = NS). However, the secondary end point of death or nonfatal MI through hospital discharge occurred in 10.0% of patients treated with 0.02 mg.kg-1.h-1 compared with 3.2% of patients treated with the three higher doses of Hirulog (0.25, 0.5, and 1.0 mg.kg-1.h-1, P = .008). Only 2 of 410 patients (0.5%) experienced a major hemorrhage attributed to Hirulog.. The direct thrombin inhibitor Hirulog is a promising new antithrombotic agent that deserves further study. The results of TIMI 7 lend support to the use of an antithrombin agent with aspirin in patients with unstable angina.

Topics: Adult; Aged; Angina, Unstable; Aspirin; Coronary Angiography; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Peptide Fragments; Pilot Projects; Recombinant Proteins; Thrombin

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

Several new anticoagulants and antiplatelet agents have been developed for use in coronary angioplasty, but almost all have been associated with an increased incidence of bleeding complications. Hirulog, a direct thrombin inhibitor, has several theoretical advantages over heparin. It is unclear, however, whether the use of hirulog as a substitute for heparin in angioplasty would result in a higher incidence of bleeding or other side effects. The safety profile of hirulog was compared with that of heparin in a randomized, double-blind trial in 4312 patients who were scheduled to undergo angioplasty for unstable or postinfarction angina. The goal of anticoagulation was to achieve an activated clotting time of approximately 350 seconds with hirulog (bolus dose of 1.0 mg/kg body weight followed by a 4-hour infusion of 2.5 mg/kg per hour and a 14- to 20-hour infusion of 0.2 mg/kg per hour) or heparin (bolus dose of 175 units/kg followed by an 18- to 24-hour infusion of 15 units/kg per hour). Adverse events were recorded prospectively by study personnel and confirmed independently by clinical monitors blinded to treatment assignment. Compared with heparin in an intention-to-treat analysis, hirulog therapy was associated with either equivalent or lower rates of side effects. Most of the side effects of hirulog and heparin were related to hemorrhagic complications such as intravascular puncture site hemorrhage (29.1% vs 61.6%; p < 0.001), hematuria (16.6% vs 20.6%; p = 0.001), bleeding requiring red cell transfusion (3.7% vs 8.6%; p < 0.001), or hematemesis (0.8% vs 1.9%; p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Double-Blind Method; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Prospective Studies; Recombinant Proteins; Safety; Time Factors

An improved survival rate is a consequence of successful reperfusion of the infarct-related artery. This double-blind, randomized trial investigated the potential of Hirulog, a direct thrombin inhibitor, to improve the early patency rates obtained with streptokinase and aspirin.. Angiographic patency of the culprit coronary artery lesion was assessed 90 and 120 minutes after the initiation of streptokinase and aspirin and again after 4 +/- 2 days in 68 patients with acute myocardial infarction. Patients were randomized to Hirulog 0.5 mg/kg per hour for 12 hours followed by 0.1 mg/kg per hour (low dose), Hirulog 1.0 mg/kg per hour for 12 hours followed by placebo (high dose), or to heparin 5000 U bolus followed by 1000 U/h titrated to an activated partial thromboplastin time (aPTT) 2 to 2.5 times control after 12 hours. At 90 minutes, TIMI flow grade 2 or 3 was observed in 96% of patients treated with the low dose of Hirulog, in 79% with the high dose, and in 46% with heparin (P = .006) and TIMI flow grade 3 was observed in 85%, 61%, and 31% of patients, respectively (P = .008). At 120 minutes, these figures were 100%, 82%, and 62% for TIMI flow grades 2 and 3 (P = .046) and 92%, 68%, and 46% for TIMI flow grade 3 (P = .014). At 90 minutes, the relative risk for restoring TIMI flow grade 3 was 2.77 with Hirulog 0.5 mg/kg per hour compared with heparin (95% confidence limits, 1.21 to 6.35; P < .001) and 1.4 compared with Hirulog 1.0 mg/kg per minute (95% confidence limits, 1.00 to 1.51; P = .04). Patients who received a placebo infusion after 12 hours experienced more clinical events and reocclusion during the following 4 days than patients in the other two groups.. Hirulog yields higher early patency rates in the culprit coronary artery than heparin when used as adjunctive therapy to streptokinase and aspirin in the early phase of acute myocardial infarction. High doses are not required and may be less effective than lower doses, which suggests that too much thrombin inhibition may be harmful.

Topics: Aspirin; Cardiac Catheterization; Coronary Angiography; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Streptokinase; Survival Rate; Thrombin; Vascular Patency

The success of streptokinase in acute myocardial infarction is hampered by the high failure rate to achieve early reperfusion. This study evaluates the possible benefit of Hirulog (Biogen, Cambridge, Mass), a direct thrombin inhibitor, as adjunct therapy to streptokinase to enhance early patency and prevent rethrombosis. Heparin has been shown to be of very limited benefits in this setting.. Forty-five patients were randomized to Hirulog or heparin (2:1 ratio). Coronary angiography documented a TIMI 2 or 3 flow after 90 minutes in 77% of the patients treated with Hirulog and streptokinase and in 47% of patients treated with heparin and streptokinase (P < .05) and after 120 minutes in 87% and 47% of patients, respectively (P < .01). TIMI 3 flow was established in 77% of patients with Hirulog compared with 40% with heparin (P < .02). The clinical outcome and the bleeding rate was also favorable to Hirulog; no reocclusion was observed at late angiography performed 4.7 days later.. Hirulog in this pilot study significantly improved the early patency rate of the infarct-related artery with a favorable clinical profile. This new direct thrombin inhibitor exhibits promise as adjunctive therapy to thrombolysis.

Topics: Coronary Angiography; Double-Blind Method; Drug Therapy, Combination; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Partial Thromboplastin Time; Peptide Fragments; Pilot Projects; Recombinant Proteins; Single-Blind Method; Streptokinase; Thrombin; Time Factors; Vascular Patency

Topics: Antithrombins; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; ST Elevation Myocardial Infarction; 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

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

Background To understand when results from observational studies and randomized trials are comparable, we performed an observational emulation of a target trial designed to ask similar questions as the VALIDATE (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy) randomized trial. The VALIDATE trial compared the effect of bivalirudin and heparin during percutaneous coronary intervention on the risk of death, myocardial infarction, and bleeding across Sweden. Methods and Results We specified the protocol of a target trial similar to the VALIDATE trial, then emulated the target trial in the period before the VALIDATE trial took place using data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry-the same registry in which the trial was undertaken. The target trial emulation and the VALIDATE trial both estimated little or no effect of bivalirudin versus heparin on the risk of death or myocardial infarction by 180 days (target trial emulation risk ratio for death, 1.21 [95% CI, 0.88 - 1.54]; VALIDATE trial hazard ratio for death, 1.05 [95% CI, 0.78 - 1.41]). The observational data, however, could not capture less severe cases of bleeding, resulting in an inability to define a bleeding outcome like the trial, and could not accurately estimate the comparative risk of death by 14 days, which may be the result of intractable confounding early in follow-up or the inability to precisely emulate the trial's eligibility criteria. Conclusions Using real-world data to emulate a target trial can deliver accurate effect estimates. Yet, even with rich observational data, it is not always possible to estimate the short-term effect of interventions or the effect on outcomes for which data are not routinely collected.

Topics: Aged; Anticoagulants; Antithrombins; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Survival Rate; Sweden

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

Topics: Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins

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

Acute myocardial infarction (AMI) occurs when atherosclerotic lesions which present in the coronary arteries cause the intravascular plate to rupture and with the result of myocardial ischemia, hypoxia, and infarct. The preferred treatment for AMI is currently percutaneous coronary intervention (PCI), for which the key to the success is the choice of anticoagulant and thrombolytic drugs during surgery. Here, we aim to explore the effects of atorvastatin combined with bivalirudin on coagulation function, cardiac function, and inflammatory factors in elderly patients with AMI who underwent PCI.. The clinical data of 86 AMI patients who were admitted to our hospital between February 2016 and May 2018 were retrospectively analyzed. Based on different treatments, the patients were divided into the control group and the observation group, with 43 patients in each group. The control group patients were treated with bivalirudin, and the observation group was treated with bivalirudin plus atorvastatin. Both groups of patients underwent PCI and the clinical efficacy, coagulation function, cardiac function, inflammatory factor levels and cardiovascular events (MACE), and other clinical data were compared between the groups.. The total clinical effective rate in the observation group was significantly higher than that in the control group (90.90% vs. 72.09%) (P<0.05). Fibrinogen (Fg) and D-dimer (D-D) levels were significantly decreased after treatment in both groups but were significantly lower in the observation group than in the control group. The prothrombin time (PT) was significantly prolonged after treatment in both groups but was significantly longer in the observation group than in the control group after treatment (P<0.05). Meanwhile, the left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were significantly reduced after treatment in both groups but were significantly lower in the observation group than in the control group, whereas the left ventricular ejection fraction (LVEF) was significantly higher in the observation group compared with the control group after treatment (P<0.05). After treatment, serum levels of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and IL-6 were significantly reduced in both groups but the levels were significantly lower in the observation group than in the control group (P<0.05). The overall incidence of MACE in the observation group was significantly lower than that in the control group (9.30% vs. 30.23%) (P<0.05).. Atorvastatin combined with bivalirudin can improve the efficiency of clinical treatment in elderly AMI patients who undergo PCI, while simultaneously improving blood coagulation function and reducing the occurrence of bleeding, compared with bivalrudin alone. It can also decrease the level of inflammatory factors, promote vascular recanalization, and improve myocardial ischemia, thereby reducing the incidence of MACE and improving patient prognosis.

Topics: Acute Disease; Aged; Atorvastatin; Blood Coagulation; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Retrospective Studies; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Glycoprotein IIb/IIIa inhibitors, used as a standard intravenous bolus followed by a prolonged infusion for 12 to 18 hours, reduces ischemic complications during percutaneous coronary interventions (PCI) but often at a cost of increased bleeding. Today, when dual oral antiplatelet therapy is routine, heparin use plus short-term (bolus alone or with a <6 hours infusion) glycoprotein IIb/IIIa inhibitors, or bivalirudin monotherapy, have been proposed as potentially superior alternatives. This observational study evaluated the safety and efficacy of heparin plus short-term tirofiban versus bivalirudin monotherapy during PCI. Patients with successful PCI and no cardiogenic shock who were anticoagulated with either of the above regimens were followed for 30-day major bleeding and major adverse cardiovascular events (death, nonfatal myocardial infarction, and urgent target vessel revascularization) at 30 days, 1 year, and long term. A total of 727 patients receiving tirofiban (age = 63 ± 13 years, males = 76%, ACS presentation = 75%, radial access = 51%) and 459 patients receiving bivalirudin, (age = 65 ± 13 years, males = 71%, ACS presentation = 78%, radial access = 18%) were included. Thirty-day major bleeding was 0.7% and 4.1% for tirofiban and bivalirudin, respectively (adjusted odds ratio = 0.17 [0.06, 0.46], p = 0.001). During 30-day, 1-year, and long-term (1.7 ± 0.9 years) follow-up, major adverse cardiovascular events risk did not differ significantly between tirofiban and bivalirudin. However, long-term death was significantly lower in those receiving tirofiban (adjusted hazard ratio = 0.58 [0.34, 1.00], p = 0.05). In conclusion, in this observational study, PCI patients receiving heparin plus short-term tirofiban experienced significantly lower 30-day major bleeding, and improved long-term survival, than those receiving bivalirudin monotherapy.

Topics: Aged; Antithrombins; Drug Administration Schedule; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Perioperative Care; Platelet Aggregation Inhibitors; Recombinant Proteins; Registries; Tirofiban; Treatment Outcome

Topics: Anticoagulants; Antithrombins; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Treatment Outcome

Topics: Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Topics: Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Topics: Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Topics: Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

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

In the last decades, several new therapies have emerged for the treatment of acute coronary syndromes (ACS). We sought to describe real-world patterns of use of antithrombotic treatments in the catheterization laboratory for ACS patients undergoing percutaneous coronary interventions (PCI).. EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in ACS patients in Italy.. Over a 3-week period, a total of 2585 consecutive ACS patients have been enrolled in 203 cardiac care units across Italy. Among these patients, 1755 underwent PCI (923 with ST-elevation myocardial infarction and 832 with non-ST-elevation ACS). In the catheterization laboratory, unfractioned heparin was the most used antithrombotic drug in both ST-elevation myocardial infarction (64.7%) and non-ST-elevation ACS (77.5%) undergoing PCI and, as aspirin, bivalirudin and glycoprotein IIb/IIIa inhibitors (GPIs) more frequently employed before or during PCI compared with the postprocedural period. Any crossover of heparin therapy occurred in 36.0% of cases, whereas switching from one P2Y12 inhibitor to another occurred in 3.7% of patients. Multivariable analysis yielded several independent predictors of GPIs and of bivalirudin use in the catheterization laboratory, mainly related to clinical presentation, PCI complexity and presence of complications during the procedure.. In our contemporary, nationwide, all-comers cohort of ACS patients undergoing PCI, antithrombotic therapies were commonly initiated before the catheterization laboratory. In the periprocedural period, the most frequently employed drugs were unfractioned heparin, leading to a high rate of crossover, followed by GPIs and bivalirudin, mainly used during complex PCI.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02015624.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Cross-Sectional Studies; Female; Heparin; Hirudins; Humans; Italy; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Registries

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

Randomized controlled trials have shown conflicting results regarding the outcome of bivalirudin in primary percutaneous coronary intervention (PPCI). The aim of this study was to evaluate the in-hospital outcomes of patients receiving heparin or bivalirudin in a real-world setting of PPCI: 7,023 consecutive patients enrolled in the Austrian Acute PCI Registry were included between January 2010 and December 2014. Patients were classified according to the peri-interventional anticoagulation regimen receiving heparin (n = 6430) or bivalirudin (n = 593) with or without GpIIb/IIIa inhibitors (GPIs). In-hospital mortality (odds ratio [OR] 1.13, 95% confidence interval [CI] 0.57 to 2.25, p = 0.72), major adverse cardiovascular events (OR 1.18, 95% CI 0.65 to 2.14, p = 0.59), net adverse clinical events (OR 1.01, 95% CI 0.57 to 1.77, p = 0.99), and TIMI non-coronary artery bypass graft-related major bleeding (OR 0.41, 95% CI 0.09 to 1.86, p = 0.25) were not significantly different between the groups. However, we detected potential effect modifications of anticoagulants on mortality by GPIs (OR 0.12, 95% CI 0.01 to 1.07, p = 0.06) and access site (OR 0.25, 95% CI 0.06 to 1.03, p = 0.06) favoring bivalirudin in femoral access. In conclusion, this large real-world cohort of PPCI, heparin-based anticoagulation showed similar results of short-term mortality compared with bivalirudin. We observed a potential effect modification by additional GPI use and access favoring bivalirudin over heparin in femoral, but not radial, access.

Topics: Antithrombins; Austria; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Hospital Mortality; Humans; Inpatients; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Registries; Survival Rate; 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

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

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

The HORIZONS trial reported a survival advantage for bivalirudin over heparin-with-glycoprotein inhibitors (GPIs) in primary PCI for ST elevation myocardial infarction. This drove an international shift in clinical practice. Subsequent studies have produced divergent findings on mortality benefits with bivalirudin. We investigated this issue in a larger population than studied in any of these trials, using the United Kingdom national PCI registry.. 61 136 primary PCI procedures were performed between January 2008 and January 2012. Demographic and procedural data were obtained from the registry. Mortality information was obtained through the UK Office of National Statistics. Multivariable logistic regression and propensity analysis modelling were utilized to study the association of different anti-thrombotic strategies with outcomes. Unadjusted data demonstrated near-identical survival curves for bivalirudin and heparin-plus-GPI groups. Significantly higher early and late mortality was found in patients treated with heparin alone ( ITALIC! P < 0.0001) but this group had a markedly higher baseline risk. After propensity matching, the bivalirudin vs. heparin-plus-GPI groups still demonstrated very similar adjusted mortality (odds ratio 1.00 at 30 days, and 0.96 at 1 year). Patients treated with heparin alone continued to show higher mortality after adjustment, although effect size was considerably diminished (odds ratio vs. other groups 1.17-1.24 at 30 days).. Analysis of recent UK data showed no significant difference in short- or medium-term mortality between ST elevation myocardial infarction patients treated with bivalirudin vs. heparin-plus-GPI at primary PCI.

Topics: Anticoagulants; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome; United Kingdom

Peripheral vascular interventions are increasingly preferred for the treatment of patients with symptomatic peripheral arterial disease because they are associated with similar clinical outcomes and lower morbidity than open surgical procedures. The objective of this study was to assess the comparative effectiveness of procedural anticoagulation with bivalirudin compared with unfractionated heparin in patients undergoing peripheral vascular interventions.. This was a retrospective, observational study using the Premier Hospital administrative database. We examined 23,934 consecutive patients undergoing lower extremity peripheral vascular interventions between January 2008 and December 2012 who were treated with either bivalirudin or unfractionated heparin. In-hospital end points included death, myocardial infarction, transfusion, stroke, amputation, and the composite end points of major adverse cardiovascular events, and net adverse clinical events. Propensity score matching was performed to control for baseline imbalances and yielded 3649 matched pairs. After propensity score matching, patients treated with bivalirudin had lower in-hospital event rates with significantly lower mortality (odds ratio, 0.40; P=0.017), need for blood product transfusion (odds ratio, 0.74; P=0.009), major adverse cardiovascular events (odds ratio, 0.64; P=0.003), and net adverse clinical events (odds ratio, 0.72; P<0.001). These associations were observed consistently across clinically relevant subgroups.. In patients undergoing peripheral vascular interventions, procedural anticoagulation with bivalirudin may result in more favorable in-hospital outcomes compared with unfractionated heparin, the current standard of care. These observations will require prospective confirmation in a randomized, controlled trial.

Topics: Aged; Anticoagulants; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heparin; Hirudins; Hospital Mortality; Humans; Incidence; Male; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Propensity Score; Recombinant Proteins; Retrospective Studies; Survival Rate; Time Factors; Treatment Outcome; United States

We aimed to assess the association of bivalirudin with post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow, acute (≤24 hours) and 30-day stent thrombosis (ST), and one-year mortality.. The study included 11,623 patients undergoing percutaneous coronary intervention (PCI). The primary outcomes were post-procedural TIMI flow grade ≤2 and definite acute ST. In groups treated with bivalirudin (n=3,135), abciximab plus unfractionated heparin (UFH; n=3,539) and UFH alone (n=4,949), post-procedural TIMI was ≤2 in 5.2%, 3.2% and 3.2% of patients, respectively (adjusted odds ratio [OR]=1.96 [95% confidence interval] 1.47-2.56 for bivalirudin versus abciximab plus UFH and OR=1.56 [1.20-2.04] for bivalirudin versus UFH). Definite acute ST occurred in two patients (0.06%) treated with bivalirudin, two patients (0.06%) treated with abciximab plus UFH, and seven patients (0.14%) treated with UFH (p=0.47). Bivalirudin was not associated with increased risk of 30-day ST (hazard ratio [HR]=1.20 [0.59-2.43] versus abciximab plus UHF, and HR=0.93 [0.48-1.82] versus UFH) or one-year mortality (HR=0.95 [0.70-1.28] versus abciximab plus UHF, and HR=1.05 [0.78-1.41] versus UFH).. Bivalirudin was associated with higher risk of suboptimal post-PCI TIMI flow but not with increased risk of acute or 30-day definite ST or one-year mortality compared with abciximab plus UFH or UFH alone.

Topics: Abciximab; Aged; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk; Stents; Thrombosis

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

Massive intracoronary thrombus is associated with adverse procedural results including failed aspiration and unfavourable reperfusion. We aim to evaluate the effect of the intracoronary administration of antithrombotic agents via a perfusion catheter in patients with ST-segment elevation myocardial infarction (STEMI) presenting with a large thrombus burden and failed aspiration.. We retrospectively analyzed the thrombus burden, the TIMI grade flow, and the myocardial Blush in 25 consecutive STEMI patients with a large thrombus burden and failed manual aspiration, who received intracoronary infusion of glycoprotein IIb/IIIa inhibitors (N=17) or bivalirudine (N=8) via a 6F-infusion catheter (ClearWay™ RX) RESULTS: Mean age was 67±14 years, 16 patients (64 %) presented with anterior STEMI, and 7 (28 %) with cardiogenic shock. Immediately after intracoronary infusion, the TIMI flow grade improved of 2 grades in 7 patients (28 %), and 1 grade in 14 (56 %), a complete resolution of the thrombus was observed in 9 patients, and a >50 % resolution in 12. Blush was improved of 3 grades in 15 patients (60 %), of 2 grades in 7 (28 %), and Blush grade 0 remained in 3. At the end of procedure, we observed normal TIMI 3flow in most patients (92 %), a complete resolution of thrombus in 80 %, and a Blush grade 3 in 68 %.. In STEMI patients presenting with a large thrombus burden and failed aspiration, intracoronary administration of glycoprotein IIb/IIIa inhibitors or bivalirudin via the perfusion catheter ClearWay™ RX significantly reduced the thrombus burden and improved the TIMI flow and the Blush grade, without bleeding.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Thrombosis; Female; Fibrinolytic Agents; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Suction; Thrombolytic Therapy; Treatment Failure

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

Topics: Antithrombins; Female; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

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

Topics: Antithrombins; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Tirofiban; Tyrosine

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

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

A 74-year-old female had urgent surgery with replacement of the ascending aorta for acute type A dissection. Postprocedure, the electrocardiogram showed an ST-segment elevation myocardial infarction in the antero-lateral leads. Angiography revealed a thrombotic occlusion of the left anterior descending artery, treated successfully with bivalirudin administration, thrombus aspiration and a balloon angioplasty. This case involves the rare coexistence of acute type A aortic dissection and myocardial infarction due to coronary plaque thrombosis.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Aorta; Aortic Aneurysm; Aortic Dissection; Coronary Angiography; Coronary Vessels; Electrocardiography; Female; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombectomy; Thrombosis; Treatment Outcome

During a myocardial infarction, no single best approach of systemic anticoagulation is recommended, likely due to a lack of comparative effectiveness studies and trade-offs between treatments.. We investigated the patterns of use and site-level variability in anticoagulant strategies (unfractionated heparin [UFH] only, low-molecular-weight heparin [LMWH] only, UFH+LMWH, any bivalirudin) of 63 796 patients with a principal diagnosis of myocardial infarction treated with an early invasive strategy with percutaneous coronary intervention at 257 hospitals. About half (47%) of patients received UFH only, 6% UFH+LMWH, 7% LMWH only, and 40% bivalirudin. Compared with UFH, the median odds ratio was 2.90 for LMWH+UFH, 4.70 for LMWH only, and 3.09 for bivalirudin, indicating that 2 "identical" patients would have a 3- to 4-fold greater likelihood of being treated with anticoagulants other than UFH at one hospital compared with another. We then categorized hospitals as low- or high-users of LMWH and bivalirudin. Using hierarchical, multivariate regression models, we found that low bivalirudin-using hospitals had higher unadjusted bleeding rates, but the risk-adjusted and anticoagulant-adjusted bleeding rates did not differ across the hospital anticoagulation phenotypes. Risk-standardized mortality and risk-standardized length of stay also did not differ across hospital phenotypes.. We found substantial site-level variability in the choice of anticoagulants for invasively managed acute myocardial infarction patients, even after accounting for patient factors. No single hospital-use pattern was found to be clinically superior. More studies are needed to determine which patients would derive the greatest benefit from various anticoagulants and to support consistent treatment of patients with the optimal anticoagulant strategy.

Topics: Aged; Anticoagulants; Female; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Hospitals; Humans; Length of Stay; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Retrospective Studies; Treatment Outcome

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

Despite major trials showing the opposite, one of three small randomized trials conducted outside the US has raised questions about whether heparin alone is a viable antithrombotic strategy for primary percutaneous coronary interventions (PPCI). We determined the frequency and in-hospital outcomes of anticoagulation strategies in patients undergoing PPCI.. We analyzed records from 2008 through 2013 in the Premier Research Database of patients hospitalized with ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. Patients were categorized into one of four anticoagulation strategies: bivalirudin alone, bivalirudin plus glycoprotein IIb/IIIa inhibitors (GPI), unfractionated or low-molecular-weight heparin alone or heparin plus GPI. In-hospital clinical outcomes were compared between treatment groups after propensity score matching.. Among 114,134 eligible STEMI patients, heparin alone was the least frequent anticoagulation strategy, used in 14.4% to 18.1% of cases per year. Bivalirudin alone nearly tripled during the study period, from 12.7% to 37.8% and surpassed that of heparin plus GPI by 2013. Bivalirudin alone performed better than heparin alone for mortality (4.7% vs 5.3%, p = 0.010), clinically apparent bleeding (5.7% vs 6.7%, p < 0.001), transfusion rates (4.1% vs 4.8%, p = 0.003) and mean length of stay (4.1 vs 4.2 days, p < 0.001). The in-hospital death rate was lower with heparin plus GPI than with heparin alone (4.9% vs 5.9%, p < 0.001), but clinically apparent bleeding was higher in heparin plus GPI than in heparin alone (9.4% vs 7.1%, p < 0.001).. In patients hospitalized for STEMI undergoing PPCI, heparin alone is not commonly used and is inferior to bivalirudin for mortality, bleeding and length of stay outcomes. Heparin is also inferior to heparin plus GPI for ischemic protection but associated with less bleeding.

Topics: Aged; Anticoagulants; Databases, Factual; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies; Survival Analysis; 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

Data on the effect of bivalirudin therapy in primary percutaneous coronary interventions (PCI) performed through the transradial approach are limited. The aim of our study was to evaluate bleeding complications and clinical outcomes in primary PCI performed through the transradial approach with bivalirudin therapy.. We retrospectively evaluated primary PCI performed through the transradial approach from January 2008 to June 2013. Patients were divided in two groups according to the use (group 1) or not (group 2) of bivalirudin. The primary end points were major bleedings and major adverse cardiac events (MACE) within 30 days.. During the 5 years analysed, 1009 patients underwent primary PCI through the transradial approach: 154 patients were treated with bivalirudin (males 79%, age 65 ± 14 years) and 855 with heparin (males 82%, 63 ± 12 years). In group 1, the use of glycoprotein IIb/IIIa inhibitors was only 4%, compared to 55% (p<0.001) in group 2. There were no significant differences between the two groups for major bleedings (0.65% in group 1 and 1.17% in group 2, p=0.88) nor for minor bleedings (1.3% in group 1 and 1.5% in group 2, p=0.83). There were also no significant differences in MACE (7.1% in group 1 and 10.4% in group 2, p=0.27). The 30-day mortality rate was 3.9% in group 1 and 5.4% in group 2 (p=0.56).. In this registry of primary PCI performed through the transradial approach, bivalirudin was not associated with a significant reduction in major bleeding or MACE compared to heparin and provisional glycoprotein IIb/IIIa inhibitors.

Topics: Aged; Anticoagulants; Antithrombins; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Hemorrhage; Prospective Studies; Recombinant Proteins; Registries; Retrospective Studies; 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

Topics: Acute Coronary Syndrome; Antithrombins; Female; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins

Topics: Acute Coronary Syndrome; Antithrombins; Female; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins

Topics: Ambulances; Anticoagulants; Antithrombins; Hirudins; Humans; Myocardial Infarction; Patient Transfer; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk; Treatment Outcome

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

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

Topics: Anticoagulants; Female; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

Topics: Anticoagulants; Clopidogrel; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticlopidine

Timely and appropriate use of antiplatelet and anticoagulant therapies has been shown to improve outcomes among ST-segment elevation myocardial infarction (STEMI) patients but has not been well described in patients transferred for primary percutaneous coronary intervention (PCI).. We examined 16,801 (26%) transfer and 47,329 direct-arrival STEMI patients treated with primary PCI at 441 Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines hospitals. Medication use was compared between transfer and direct-arrival patients to determine if these therapies were delayed or dosed in excess.. Although transfer patients were more likely to receive antiplatelet and anticoagulant therapies before catheterization, they had longer delays to initiation of heparin (35 vs. 25 minutes), clopidogrel (119 vs. 84 minutes), and glycoprotein IIb/IIIa inhibitor (107 vs. 60 minutes, P < .0001 for both). Administration of low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitor at the STEMI-referring hospital was associated with longer delays to reperfusion compared with deferred administration at the STEMI-receiving hospital, whereas early use of unfractionated heparin was not. Among treated patients, those transferred were more likely to receive excess heparin dosing (adjusted odds ratio [OR] 1.28 [95% CI 1.04-1.58] for unfractionated heparin, adjusted OR 1.54 [95% CI 1.09-2.18] for low-molecular-weight heparin) and are associated with higher risks of major bleeding complications (adjusted OR 1.10, 95% CI 1.03-1.17).. ST-segment elevation myocardial infarction patients transferred for primary PCI in community practice are at risk for delayed and excessively dosed antithrombotic therapy, highlighting the need for continued quality improvement to maximize the appropriate use of these important adjunctive therapies.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Cohort Studies; Early Medical Intervention; Female; Guideline Adherence; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Patient Transfer; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Pyridines; Recombinant Proteins; Retrospective Studies; Ticlopidine; Time-to-Treatment

Topics: Antithrombins; Cardiology; Consensus; Female; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Poland; Recombinant Proteins; Societies, Medical

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

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

Bivalirudin, a direct thrombin inhibitor, demonstrated an improvement in the prognosis of acute coronary syndromes by a decrease in major bleeding complications. This observational study evaluated inhospital outcome of patients with acute myocardial infarction treated by prehospital bivalirudin before primary angioplasty.. We included, from June 2010 to June 2012, all patients with acute myocardial infarction receiving prehospital bivalirudin with bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg per hour until the arrival in the catheterization laboratory. Bivalirudin was possibly continued after primary angioplasty.. We included 152 patients aged 57.6±11.6 years. A prehospital 60mg loading dose of prasugrel was given in 77% of patients. Coronary angiography with radial access (77.6%) was performed before a successful angioplasty in 97.3% of cases. The bivalirudin infusion was continued after the procedure in 81.6% of patients. Inhospital outcome showed two deaths (1.3%) and two re-infarctions (1.3%) of which one was related to the single acute stent thrombosis (0.6%). Major bleeding complications were limited irrespective of the Gusto (0.6%), Timi (0.6%) or Horizons-MI (4.6%) classification. Bleeding complications rate was similar when bivalirudin was followed or not after primary angioplasty.. The use of bivalirudin in the prehospital setting for primary angioplasty seems to be effective and safe about ischemic and bleeding complications during the inhospital outcome.

Topics: Aged; Angioplasty; Antithrombins; Coronary Angiography; Emergency Medical Services; Female; Hirudins; Humans; Infusion Pumps; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Risk Factors; Sex Distribution; Smoking; Treatment Outcome

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

In primary angioplasty, bivalirudin is superior to treatment with heparin plus glycoprotein inhibitors for reducing cardiovascular events, although bivalirudin increases the risk of stent thrombosis. Our hypothesis is that the use of prasugrel plus bivalirudin in primary angioplasty would reduce stent thrombosis and cardiovascular events.. Consecutive patients with acute ST-segment elevation myocardial infarction who were treated by primary angioplasty within 12 hours of the onset of symptoms received bivalirudin plus clopidogrel (Group A) or bivalirudin plus prasugrel (Group B). We compared the groups using propensity score matching. The combined end-point was cardiac death, thrombosis, acute myocardial infarction, and cerebrovascular accident at 30 days.. We assessed 168 patients. The approach was preferentially radial (95.7%). No differences in baseline characteristics were observed between Groups A (n = 70) and B (n = 70). The total mortality and rate of major bleeding complications at 30 days were 0% for both of the groups. The rate of acute and subacute thrombosis was 4.3% in Group A and 0% in Group B (P = 0.08). We observed an increased rate of events in Group A (5.7%) versus Group B (0%) (P = 0.042).. The administration of bivalirudin plus prasugrel in primary percutaneous coronary intervention reduces cardiovascular effects compared to bivalirudin plus clopidogrel without increasing major bleeding complications during the first 30 days following primary angioplasty performed with a preferentially radial approach.

Topics: Angioplasty; Antithrombins; Clopidogrel; Cohort Studies; Drug Combinations; Female; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Piperazines; Postoperative Complications; Prasugrel Hydrochloride; Recombinant Proteins; Retrospective Studies; Thiophenes; Thrombosis; Ticlopidine

Topics: Abciximab; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins

Topics: Antithrombins; Coronary Thrombosis; Female; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Thrombolytic Therapy

Topics: Antithrombins; Emergency Medical Services; Female; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

Topics: Abciximab; Antibodies, Monoclonal; Antithrombins; Blood Loss, Surgical; Cardiac Catheterization; Collagen; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Vascular Closure Devices

Topics: Antithrombins; Antitubercular Agents; Diarylquinolines; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Tuberculosis

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

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

The reperfusion injury (RI) remains a significant limitation of primary PCI, therefore we evaluated the role of intracoronary abciximab and bivalirudin for anticoagulation on myocardial salvage and RI in the porcine model of ischemia/reperfusion.. Myocardial infarction was induced in 23 pigs by 60-minute over-the-wire (OTW) balloon occlusion of the LAD. Animals received intravenous bivalirudin and then five minutes prior to reperfusion, either a coronary downstream infusion of abciximab (n=11) or saline (n=12) through the central lumen of an OTW catheter. All animals were followed for 48 hours.. Histological analysis showed that infarct area (IA) and area at risk (AAR) were comparable between groups (IA/AAR%: 57.6 ± 8% vs. 57.1 ± 7%, p=0.8). Confirming this trend, biochemical markers (troponin I, TNF-alpha, IL-6, hsCRP, adiponectin, and VCAM) and left ventricular ejection fraction were also similar at 48 hours. Adhesion markers like ICAM and P-selectin were significantly decreased in the study group, nevertheless histological evidence of leukocyte extravasation was similar. The enhancement of apoptosis by TUNEL was comparable in both groups. The number of hemorrhagic infarctions confirmed by micro and macroscopic evaluation tended to be higher in the study group (70% vs. 20%, p=0.07).. Despite lowered concentrations of adhesion molecules, intracoronary abciximab with peripheral bivalirudin is not superior to bivalirudin unaided in terms of myocardial salvage caused by RI in the porcine ischemia/reperfusion model. This might be due to local hemorrhage caused by abciximab.

Topics: Abciximab; Animals; Antibodies, Monoclonal; Anticoagulants; CD40 Ligand; Drug Combinations; Female; Hirudins; Immunoglobulin Fab Fragments; Intercellular Adhesion Molecule-1; Male; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Peptide Fragments; Recombinant Proteins; Swine; Vascular Cell Adhesion Molecule-1

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

Topics: Antithrombins; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Practice Guidelines as Topic; Recombinant Proteins

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: 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

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: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Magnetic Resonance Imaging, Cine; Male; Myocardial Infarction; Myocardium; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Clopidogrel; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Myocardial Infarction; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Recombinant Proteins; Stents; Ticlopidine

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

Cell therapy is a promising option for the treatment of acute or chronic myocardial ischemia. The intracoronary infusion of cells imposes the potential risk of cell clotting, which may be prevented by the addition of anticoagulants. However, a comprehensive analysis of the effects of anticoagulants on the function of the cells is missing.. Here, we investigated the effects of heparin and the thrombin inhibitor bivalirudin on bone marrow-derived mononuclear cell (BMC) functional activity and homing capacity.. Heparin, but not bivalirudin profoundly and dose-dependently inhibited basal and stromal cell-derived factor 1 (SDF-1)-induced BMC migration. Incubation of BMCs with 20 U/mL heparin for 30 minutes abrogated SDF-1-induced BMC invasion (16±8% of control; P<0.01), whereas no effects on apoptosis or colony formation were observed (80±33% and 100±44% of control, respectively). Pretreatment of BMCs with heparin significantly reduced the homing of the injected cells in a mouse ear-wound model (69±10% of control; P<0.05). In contrast, bivalirudin did not inhibit in vivo homing of BMCs. Mechanistically, heparin binds to both, the chemoattractant SDF-1 and its receptor, chemokine receptor 4 (CXCR4), blocking CXCR4 internalization as well as SDF-1/CXCR4 signaling after SDF-1 stimulation.. Heparin blocks SDF-1/CXCR4 signaling by binding to the ligand as well as the receptor, thereby interfering with migration and homing of BMCs. In contrast, the thrombin inhibitor bivalirudin did not interfere with BMC homing or SDF-1/CXCR4 signaling. These findings suggest that bivalirudin but not heparin might be recommended as an anticoagulant for intracoronary infusion of BMCs for cell therapy after cardiac ischemia.

Topics: Animals; Anticoagulants; Antithrombins; Bone Marrow Cells; Cell Movement; Cell- and Tissue-Based Therapy; Cells, Cultured; Chemokine CXCL12; Disease Models, Animal; Female; Heparin; Hirudins; Humans; In Vitro Techniques; Leukocytes, Mononuclear; Mice; Mice, Inbred Strains; Myocardial Infarction; Peptide Fragments; Receptors, CXCR4; Recombinant Proteins; Signal Transduction

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

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

Bivalirudin reduces bleeding events and is associated with a lower mortality than the combination of unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitor during primary percutaneous coronary intervention (PCI). However, the effect of adding UFH in patients with ST elevation myocardial infarction (STEMI) treated with bivalirudin during primary PCI is unknown.. Patients enrolled in the national Swedish Coronary Angiography and Angioplasty Registry who underwent primary PCI due to STEMI with bivalirudin as anticoagulant were evaluated. Patients were divided into two groups: those treated with bivalirudin only and those treated with bivalirudin plus a bolus dose of UFH.. 2996 patients were included in the study: 1928 (64%) received only bivalirudin and 1068 (36%) received bivalirudin plus a bolus dose of UFH. The primary combined endpoint of death or target lesion thrombosis at 30 days occurred more often in the bivalirudin group (11.3% vs 6.5%, OR 0.55, 95% CI 0.41 to 0.72, p<0.001). This difference remained significant after adjustment (HR 0.64, 95% CI 0.44 to 0.95, p=0.03). Death at 30 days and definite target lesion thrombosis at 30 days did not differ between the two groups after adjustment (9.2% vs 5.1%, adjusted HR 0.66, 95% CI 0.42 to 1.03, p=0.07 and 2.3% vs 1.5%, adjusted HR 0.59, 95% CI 0.27 to 1.33, p=0.21, respectively).. An additional bolus dose of UFH is associated with a lower rate of death or definite target lesion thrombosis at 30 days in patients undergoing primary PCI with bivalirudin as anticoagulant.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Angiography; Coronary Thrombosis; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIb-IX Complex; Recombinant Proteins

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

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Thrombosis; Female; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Anticoagulation therapy for cardiopulmonary bypass in patients with recently diagnosed heparin-induced thrombocytopenia can be particularly challenging. Although heparin is the standard of care, in these situations anticoagulation is achieved with alternative agents such as direct thrombin inhibitors. Therapeutic concentrations are difficult to assess with direct thrombin inhibitors, and their use is riddled with bleeding and thrombotic complications. We report the successful use of a specific chromogenic antifactor IIa assay in a patient with heparin-induced thrombocytopenia who received anticoagulation therapy with bivalirudin during cardiopulmonary bypass for coronary artery bypass graft surgery.

Topics: Aged; Antithrombins; Cardiopulmonary Bypass; Coronary Artery Bypass; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Heparin; Hirudins; Humans; Infusions, Intravenous; Male; Monitoring, Intraoperative; Myocardial Infarction; Peptide Fragments; Peripheral Vascular Diseases; Preoperative Care; Radiography; Recombinant Proteins; Thrombocytopenia; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Drug-Eluting Stents; Fibrinolytic Agents; Hirudins; Humans; Myocardial Infarction; Paclitaxel; Peptide Fragments; Prosthesis Design; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombosis; Time Factors; Treatment Outcome

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

To evaluate the effectiveness and safety of bivalirudin as used in routine care. Bivalirudin has been studied as an alternative to heparin plus glycoprotein IIb/IIIa inhibitor (GPI) during percutaneous coronary intervention (PCI). Trials have indicated that bivalirudin is non-inferior to heparin with respect to death and repeat revascularization and may decrease the risk of major bleeds. The use of bivalirudin in routine care has not been evaluated.. Using a representative database, we identified 127 185 individuals who underwent inpatient PCI between June 2003 and December 2006 and were administered either bivalirudin plus provisional GPI or the comparator, heparin plus GPI. We estimated relative risks of blood transfusion, repeated PCI, and in-hospital death. The adjusted hazard ratio (HR) for blood transfusion was 0.67 (0.61-0.73); instrumental variable analysis showed an HR of 0.72 (0.12-4.47). We observed a risk of in-hospital death of 0.80% in the bivalirudin group and 2.1% in the heparin group; the adjusted HR was 0.51 (0.44-0.60).. In our non-randomized study of routine care, we observed a reduction in blood transfusions and in short-term mortality for patients treated with bivalirudin compared with heparin plus GPI. The mortality benefit was more pronounced in our study than in randomized trials.

Topics: Acute Coronary Syndrome; Angioplasty; Antithrombins; Cohort Studies; Female; Hirudins; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Treatment Outcome; United States

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

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Stents; Ticlopidine; 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

This study sought to evaluate the short- and long-term efficacy and safety of bivalirudin in diabetic patients undergoing percutaneous coronary intervention (PCI) in contemporary clinical practice.. Early trials of platelet glycoprotein (GP) IIb/IIIa inhibitors have suggested a survival benefit in diabetic patients undergoing PCI. More recently, randomized trials have demonstrated that diabetic patients have similar protection from acute ischemic events, while lowering the risk of bleeding complications, when treated with bivalirudin monotherapy versus heparin plus GP IIb/IIIa blockade. However, the impact of bivalirudin use on long-term outcomes in diabetic patients undergoing PCI remains unclear.. Using the Cornell Angioplasty Registry, we studied 786 consecutive diabetic patients undergoing urgent or elective PCI with a mean clinical follow up of 24.6 +/- 7.8 months. Of these, 428 patients (54.5%) received bivalirudin monotherapy and 358 patients (45.5%) received unfractionated heparin (UFH) plus GP IIb/IIIa inhibition. The incidence of in-hospital death (0% vs. 0.3%; p = 0.46), post-procedural myocardial infarction (MI) (4.7% vs. 7.0%; p = 0.169), and major adverse cardiovascular events (MACE) (death, MI, stroke or urgent revascularization) (4.9% vs. 7.3%; p = 0.176) was similar in the two groups, with less minor bleeding (9.6% vs. 14.5%; p = 0.035) in the bivalirudin vs. UFH plus GP IIb/IIIa inhibitor group, respectively. By the end of follow up, there were 38 (8.9%) deaths in the bivalirudin vs. 19 (5.3%) deaths in the GP IIb/IIIa inhibitor arm (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.0-3.1; p = 0.04). However, after a propensity score-adjusted multivariate Cox regression analysis, there was no longer a significant difference in long-term mortality between the two groups (HR 1.63; chi(2) = 2.61; 95% CI 0.90-2.94; p = 0.106).. These findings indicate that in diabetic patients, bivalirudin monotherapy results in similar protection from acute ischemic events and long-term mortality, while lowering the risk of minor bleeding in comparison to UFH plus GP IIb/IIIa inhibition.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Diabetes Complications; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Infusions, Intravenous; Logistic Models; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Registries; Retrospective Studies; Stroke; Treatment Outcome

Bivalirudin is a direct thrombin inhibitor that seems to be a promising anticoagulation treatment in patient with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). We discuss several issues that were raised from the use of Bivalirudin during primary PCI.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Reproducibility of Results; Research Design

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

Gastrointestinal bleeding (GIB) complicating percutaneous coronary intervention (PCI) results in high mortality, but clinical factors associated with and long-term outcomes of GIB are poorly understood. We sought to examine clinical and procedural factors associated with GIB complicating PCI. We also examined the impact of GIB on 30-day mortality and 1-year major adverse cardiac events (MACEs). Patients undergoing PCI from January 2000 to January 2010 were retrospectively analyzed for the occurrence of in-hospital GIB. Multivariable logistic regression and Cox proportional hazards regression were used to identify predictors of in-hospital GIB and 30-day mortality. Landmark analysis of patients surviving to hospital discharge was performed to assess the impact of GIB on 1-year MACEs. Of 20,621 patients who underwent PCI, 147 (0.72%) who developed in-hospital GIB were identified. Variables associated with increased risk of GIB included older age, shock, acute myocardial infarction, chronic renal insufficiency, lower baseline hematocrit, and glycoprotein IIb/IIIa inhibitors; bivalirudin decreased the risk. Unadjusted 30-day mortality rate of patients with GIB was 20.5% compared to 2.4% of patients without GIB. After multivariable adjustment, GIB and shock (and an interaction between the 2) were the most important correlates of 30-day mortality. In the population surviving to discharge, however, GIB was not associated with adjusted mortality or MACEs. In conclusion, GIB complicating PCI has a dramatic impact on 30-day mortality, and bivalirudin was associated with lower rates of GIB.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Blood Transfusion; Drug-Eluting Stents; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hirudins; Humans; Incidence; Inpatients; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Postoperative Hemorrhage; Prognosis; Recombinant Proteins; Retrospective Studies; Risk Factors; Survival Rate; Time Factors; United States

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

No reflow, defined as failure to restore normal myocardial blood flow despite removal of coronary obstruction, is a not rare complication of ST-elevation acute myocardial infarction. We here describe the case of an old patient experiencing inferior and right ventricle myocardial infarction complicated by cardiogenic shock, anaemia and thrombocytopenia. We managed it with urgent PCI using thrombus aspirator, that determined onset of no reflow, that we successfully managed with intracoronary bivalirudin. We showed how bivalirudin, a drug whose use is increasing in the catheterization laboratories, could be safely used via the intracoronary route to treat no reflow phenomenon due to distal microembolization in a complex patient.

Topics: Aged, 80 and over; Anticoagulants; Cardiac Catheterization; Coronary Circulation; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Radiography; Recombinant Proteins

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

The objective of this study is to analyze the clinical outcomes and treatment strategies of coronary wire perforations (WPs) in the era of heparin use compared to the era of bivalirudin use.. Percutaneous coronary intervention (PCI) advances have led to progressive decrease in complications. Therefore, complex coronary lesions such as chronic total occlusions and calcified lesions are being attempted with stiff/hydrophilic wires with resultant higher incidence of coronary WP.. A single-center retrospective data analysis of coronary perforation (CP) for the last 4 years with review of coronary angiograms was done and WPs were identified. A simple classification scheme based on angiographic appearance of CP was made: Type I ("myocardial stain," with no frank dye extravasation) and type II ("myocardial fan," with dye extravasation to pericardial cavity or cardiac chambers).. Overall incidence of CP was 0.49% (82/16,859). Of these 50 (61%) were caused by WP; 30 occurred with heparin use (Group A) and 20 with bivalirudin use (Group B). WPs always occurred in type B2/C lesions (100%) and commonly with use of hydrophilic guidewires (70%). Major adverse cardiac events and cardiac tamponade were frequent in group A (50%) and none in group B (0%); P < 0.01. All WP in group B responded to stopping anticoagulation and prolonged balloon inflation, while group A type II perforations frequently required additional interventions (pericardiocentesis, coil embolization).. Cardiac tamponade and major adverse cardiac events from WPs were less frequent with bivalirudin use compared to heparin use. This beneficial effect of bivalirudin may be explained on the basis of its short half-life and reversible thrombin inhibition property. Therefore, bivalirudin may offer a safer alternative for anticoagulation in complex PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Balloon Occlusion; Cardiac Tamponade; Cineangiography; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Heparin; Heparin Antagonists; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Pericardiocentesis; Recombinant Proteins; Registries; Retrospective Studies; Treatment Outcome; Wounds, Penetrating

The selective thrombin inhibitor bivalirudin with a provisional glycoprotein IIb/IIIa inhibitor (GPI) has been shown to be comparable to heparin plus GPI in the rates of ischemic events but to significantly reduce the risk of bleeding complications in patients with acute coronary syndromes. The aim of this preliminary study was to describe the feasibility and safety of a switch from prehospital administration of unfractionated heparin to bivalirudin in ST-elevation acute myocardial infarction (STEMI) patients referred for primary percutaneous coronary intervention. Patients with STEMI treated with a 1-mg/kg bivalirudin bolus in the ambulance followed by infusion during angiography/primary percutaneous coronary intervention were compared with a STEMI control group (from the preceding year) treated with 10,000 U unfractionated heparin in the ambulance followed by in-hospital treatment with a GPI. A total of 102 patients (59%) receiving bivalirudin and 72 receiving heparin were followed during hospitalization. The baseline characteristics and prehospital treatment times were comparable between the 2 groups. The thrombolysis in myocardial infarction flow before and after primary percutaneous coronary intervention was similar. Stents were used significantly more often in the heparin-treated patients (90% versus 76%; p = 0.04), with bailout GPI for those receiving bivalirudin occurring in 30% compared with 83% of those receiving heparin (p <0.001). Significant bleeding complications were seen in <10% of all patients undergoing angiography with no difference between groups. Bivalirudin was easy to administer in the prehospital setting and did not affect the prehospital run times. In conclusion, the results suggest that prehospital bivalirudin administration is as safe and effective as heparin in the treatment of patients with STEMI. Prehospital administration seemed to reduce the need for GPI.

Topics: Anticoagulants; Antithrombins; Dose-Response Relationship, Drug; Electrocardiography; Emergency Medical Services; Feasibility Studies; Female; Follow-Up Studies; Hirudins; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Pilot Projects; Prospective Studies; Recombinant Proteins; 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: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Practice Guidelines as Topic; Recombinant Proteins; Stents; Thrombosis

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Balloon Occlusion; Blood Coagulation; Cardiac Tamponade; Coronary Vessels; Heparin; Heparin Antagonists; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pericardiocentesis; Recombinant Proteins; Treatment Outcome; Wounds, Penetrating

We report on a case of non-ST-segment myocardial infarction in the absence of coronary artery disease, caused by coronary embolism from the left atrial appendage. Due to the fact that the angiographically confirmed embolus did not resolve within 4 days of treatment with aspirin, clopidogrel and low molecular weight heparin (LMWH), we intravenously administered bivalirudin instead of LMWH for another 2 days and could demonstrate complete resolution of the embolus following this protocol. No bleeding complications or recurrence of myocardial ischemia occurred. Our observations may draw attention to bivalirudin therapy for coronary emboli, when LMWH is not effective.

Topics: Anticoagulants; Atrial Appendage; Coronary Thrombosis; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

To summarize key changes in the 2007 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations for pharmacologic therapy as they relate to antiplatelets and anticoagulants, and to evaluate the evidence from several landmark trials that was used to support the guideline updates for these agents.. Literature was accessed through MEDLINE (1950-January 2008) using the search terms acute coronary syndromes, unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), antiplatelet, and anticoagulant. All papers were cross-referenced to identify additional studies.. ACC/AHA guidelines, relevant original research articles, and review articles were evaluated. Studies with more than 1000 patients were the focus of the review.. UA and NSTEMI are the most common presentations of acute coronary syndrome. The recently updated ACC/AHA guidelines for management of this condition were based on significant advances in pharmacotherapy including expanded use of drug-eluting stents, pretreatment with clopidogrel, and newer anticoagulants such as bivalirudin and fondaparinux. Landmark trials have been published that describe advances in the use of antiplatelets and anticoagulants. According to the guidelines, unfractionated heparin (UFH) and enoxaparin are preferred options for both invasive and conservative management. Enoxaparin was noninferior to UFH for invasive management in the SYNERGY trial, although it was associated with a higher incidence of bleeding. Other alternatives for an invasive strategy per the guidelines include bivalirudin and fondaparinux. Bivalirudin (alone or with glycoprotein [GP] IIb/IIIa inhibitor) was compared with heparin plus GP IIb/IIIa inhibitor in the ACUITY trial of patients undergoing early invasive management. The bivalirudin groups were noninferior to standard of care, although bivalirudin alone was associated with less bleeding. Fondaparinux was found to be noninferior to enoxaparin and was associated with fewer bleeding events in the OASIS-5 study of patients who were not treated with an early invasive approach. Accordingly, the guidelines 1list fondaparinux as an alternative for a conservative strategy or in patients at increased risk of bleeding.. Clinicians should be familiar with the updated 2007 ACC/AHA guidelines and the clinical trial evidence that serves as the basis for these recommendations. It is paramount for institutions to outline a preferred and consistent treatment approach. These decisions should involve a review of established efficacy, bleeding risk, need for anticoagulant reversal, costs, and clinician familiarity with different treatment regimens.

Topics: American Heart Association; Angina, Unstable; Anticoagulants; Clopidogrel; Drug-Eluting Stents; Enoxaparin; Fondaparinux; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Practice Guidelines as Topic; Recombinant Proteins; Ticlopidine; United States

In patients undergoing percutaneous coronary intervention (PCI), clinical trials have demonstrated that the use of bivalirudin with provisional glycoprotein IIb/IIIa inhibitors is not inferior to heparin with systematic glycoprotein IIb/IIIa inhibitors on major adverse cardiac events and is associated with lower rates of bleeding in various clinical settings. Patients with cardiogenic shock (CS), however, have been excluded from all pivotal trials. A retrospective analysis of 86 consecutive patients undergoing PCI for acute myocardial infarction complicated by CS in our center from April 2003 to September 2007 was performed. In-hospital death, major adverse cardiac events, and bleeding rates were compared in 37 patients who received bivalirudin with or without glycoprotein IIb/IIIa inhibitors and 49 patients who were treated with heparin and glycoprotein IIb/IIIa inhibitors as anticoagulation management. Baseline demographic, clinical, and biological characteristics were similar in the 2 groups. The in-hospital death rate was significantly lower in the bivalirudin group (5.4 vs 32.7%, p = 0.002). There were no differences in the rate of major hematoma between the bivalirudin group and the heparin group (3 vs 2.6%, p = 0.46). In conclusion, bivalirudin with provisional use of glycoprotein IIb/IIIa inhibitors appears to be a safe and effective anticoagualtion strategy in patients undergoing primary PCI for acute myocardial infarction complicated by CS.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Integrin beta3; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Membrane Glycoprotein IIb; Recombinant Proteins; Shock, Cardiogenic; Treatment Outcome

Routine aspiration thrombectomy (AT) in percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction (STEMI) has not proved effective in randomized trials. However, in patients undergoing primary percutaneous coronary intervention with severely reduced flow or visible thrombus, AT remains an intuitively attractive option. The use of adjunctive AT in a high-risk cohort of 158 consecutive patients with STEMI and Thrombolysis In Myocardial Infarction (TIMI) 0 to 1 flow or visible thrombus on baseline angiography was examined. Of these, 80 patients underwent AT as an adjunct to primary percutaneous coronary intervention, and 78 underwent percutaneous coronary intervention without AT (non-AT). TIMI 3 flow rates, residual thrombus after percutaneous coronary intervention, and major adverse cardiac events (mortality and nonfatal Q-wave myocardial infarction) at 30 days, 6 months, and 1 year were compared. Baseline characteristics were similar between groups. The AT group more frequently achieved TIMI 3 flow after the intervention (91.3% AT vs 67.9% non-AT; p <0.001) and had less residual thrombus (7.5% AT vs 19.2% non-AT; p = 0.03). AT was associated with reduced major adverse cardiac events at 6 months (6.8% AT vs 24.0% non-AT; p = 0.004) and 1 year (16.6% AT vs 29.2% non-AT; p = 0.009), and decreased mortality rates in the AT group at 6 months (5.4% AT vs 21.3% non-AT; p = 0.004) and 1 year (7.7% AT vs 26.2% non-AT; p = 0.005). In conclusion, for patients with STEMI and TIMI 0 or 1 flow or visible thrombus on baseline angiography, AT was associated with increased TIMI 3 flow rates, decreased residual thrombus, and decreased clinical events, including mortality.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Case-Control Studies; Coronary Angiography; Coronary Circulation; Coronary Thrombosis; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombectomy; Treatment Outcome

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: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Combined Modality Therapy; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Recurrence; Research Design; Stents; Thrombosis

Maintaining a therapeutic level of anticoagulation with unfractionated heparin remains a major challenge for clinicians because of the wide variability of patient responses, which may be explained by variable binding of heparin to plasma proteins. Direct thrombin inhibitors may offer an advantage in more predictable anticoagulation.. Plasma samples from normal volunteers, stable coronary artery disease (CAD) patients, unstable angina patients, and acute myocardial infarction patients were obtained. A fixed concentration of heparin (.13 U/ml) or bivalirudin (1.6 microg/ml) was added to plasma from each of the four study groups and measurement of the APTT was performed. In addition, a pool of plasma from patients with acute MI was diluted in pooled normal plasma, and heparin or bivalirudin was added to the plasma preparation and APTT measurements performed.. In heparin-treated plasma samples, mean APTT values were 443 +/- 137% baseline for normal volunteers, 347 +/- 116% for patients with stable CAD, 290 +/- 124% for patients with unstable angina (p < 0.05), and 230 +/- 120% for patients with acute MI (p < 0.05). APTT did not differ across the four groups treated with bivalirudin. There was a much higher degree of variability in APTT values in heparin treated controls (272%-671%, SD approximately 30%) compared to bivalirudin treated controls (284-499%, SD approximately 12%). When the "acute MI pool" was diluted in pooled normal plasma at fixed concentrations of either bivalirudin (1.6 mug/ml) or heparin (0.13 U/ml), there was a sharp decrease in heparin activity from 407% baseline (at 0% acute MI pool) to values as low as 126% baseline (at 100% acute MI pool). A markedly different pattern was seen in the bivalirudin treated samples, where a trend towards decreased APTT values was seen only at the 100% acute MI pool.. Both heparin variability and resistance may limit optimal antithrombotic therapy with heparin in patients with ACS and constitutes a potential advantage of direct antithrombin blockade with bivalirudin.

Topics: Aged; Angina, Unstable; Anticoagulants; Case-Control Studies; Coronary Artery Disease; Drug Resistance; Female; Heparin; Hirudins; Humans; In Vitro Techniques; Male; Middle Aged; Myocardial Infarction; Partial Thromboplastin Time; Peptide Fragments; Recombinant Proteins

The use of bivalirudin in percutaneous coronary interventions has been shown to be clinically safe and effective, and may be associated with shorter hospital stays and lower costs than heparin + glycoprotein (GP) IIb/IIIa inhibition. This study compared the utilization, clinical outcomes and costs associated with the planned use of bivalirudin versus heparin + GP IIb/IIIa inhibition in drug-eluting stent (DES) patients without acute myocardial infarction (MI).. We retrospectively studied 1,842 patients who underwent DES placement between May 2003 and December 2004. Planned treatment with heparin + GP IIb/IIIa inhibition was administered to 1,305 and planned bivalirudin alone was administered to 537 patients. Clinical follow ups (mean = 782 +/- 204 days) were obtained via telephone or mailed surveys in 1,813 patients (98.4%). Propensity analysis was utilized to adjust for between-groups baseline differences.. The unadjusted data revealed similar in-hospital outcomes in both groups. After propensity adjustment, the rate of vascular complications was significantly lower in the bivalirudin-treated group (0.2% vs. 1.2%; p = 0.04). At 1 year, clinical outcomes were similar in both groups. The overall unadjusted and adjusted cost analysis revealed similar mean hospital costs (11,384 U.S. dollars vs. 11,018 U.S. dollars; p = ns) and length of stay (2.9 days vs. 2.8 days; p = ns) in both groups. The unadjusted and adjusted mean hospital costs were significantly lower in patients treated with bivalirudin versus patients who received heparin + abciximab.. These observations suggest that bivalirudin is a safe, cost-effective alternative to heparin + GP IIb/IIIa inhibition in patients undergoing DES in the absence of acute MI.

Topics: Abciximab; Aged; Antibodies, Monoclonal; Anticoagulants; Coronary Artery Disease; Costs and Cost Analysis; Drug Delivery Systems; Drug Therapy, Combination; Eptifibatide; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Immunosuppressive Agents; Length of Stay; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Sirolimus; Stents; Tirofiban; Treatment Outcome; Tyrosine

Topics: Anticoagulants; Coronary Artery Disease; Costs and Cost Analysis; Drug Delivery Systems; Heparin; Hirudins; Humans; Immunosuppressive Agents; Length of Stay; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Sirolimus; Stents

Multiple antithrombotic options are available for patients undergoing primary percutaneous coronary interventions for stent thrombosis elevation acute myocardial infarction. Current utilization and outcomes of antithrombotic agents for primary percutaneous coronary intervention, including bivalirudin, have not been defined.. A total of 84 471 patients were reported from 439 hospitals to the National Registry of Myocardial Infarction-5 registry between April 2004 and June 2005. Consecutive patients undergoing primary percutaneous coronary interventions for stent thrombosis elevation acute myocardial infarction (n=7629 at 231 United States percutaneous coronary intervention capable hospitals) comprised the population analyzed. We examined antithrombotic strategies and the occurrence of adverse cardiac events stratified according to the use of bivalirudin. Logistic regression was performed to control for differences between three antithrombotic therapy treatment groups.. Glycoprotein IIbIIIa inhibitors were used nearly ubiquitously, but given prior to percutaneous coronary interventions in only 36% of patients. Less than one-quarter of patients received clopidogrel prior to percutaneous coronary interventions. Bivalirudin was used in 4.2% of patients (n=320) undergoing primary percutaneous coronary intervention during this time period. Patients treated with bivalirudin were more likely to be elderly (P=0.03), have a history of prior bleeding (P=0.003) and stroke (P=0.06). Major adverse events and bleeding complications were similar in antithrombotic therapy groups (bleeding: bivalirudin 7.8% versus nonbivalirudin 7.5%, P=0.85). The adjusted outcomes were also similar after confining the analysis to bivalirudin patients who had not received any glycoprotein IIbIIIa inhibitors (n=143).. Contemporary primary percutaneous coronary intervention includes mainly clopidogrel and eptifibatide initiated at the time of percutaneous coronary intervention. Patients who received bivalirudin were at higher risk and had similar adjusted outcomes as patients in the nonbivalirudin group. Optimization of primary percutaneous coronary intervention pharmacology requires future randomized clinical trials, examining the timing and type of adjunctive antithrombotic agents.

Topics: Acute Disease; Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Thrombosis; Drug Utilization; Female; Hirudins; Humans; Incidence; Logistic Models; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Registries; Risk Assessment; Stents; Treatment Outcome; United States

The standard agent used for systemic anticoagulation during cardiopulmonary bypass is heparin. Alternative methods of anticoagulation are required for patients with heparin hypersensitivity. We present the case of a patient with heparin hypersensitivity who was anticoagulated with bivalirudin during cardiopulmonary bypass for coronary artery bypass grafting. This presented unusual challenges surrounding the monitoring of anticoagulation and the method of myocardial protection.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Combined Modality Therapy; Coronary Artery Bypass; Coronary Stenosis; Drug Hypersensitivity; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Ventricular Dysfunction, Left; Ventricular Fibrillation

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

To describe data and insights from a national quality improvement initiative known as Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines (CRUSADE), for managing non-ST-segment elevation acute coronary syndrome (ACS), as well as the findings and implications of Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY), a study of bivalirudin with or without a glycoprotein (GP) IIb/IIIa inhibitor in patients with non-ST-segment elevation ACS who were undergoing an invasive intervention, and the results of two recent studies of clopidogrel in patients with ST-segment elevation myocardial infarction (MI) that are not reflected in current ACC/AHA guidelines for managing ST-segment elevation MI.. Data from the CRUSADE registry suggest that there is room for improvement in the use of GP IIb/IIIa inhibitors and clopidogrel during the first 24 hours of hospitalization in patients with non-ST-segment elevation ACS who undergo early invasive cardiac procedures, and in the prescribing of angiotensin converting-enzyme (ACE) inhibitors at the time of discharge. Adherence to ACC/AHA guidelines for non-ST-segment elevation ACS has improved over time but further improvement is needed. Failure to reduce the dose of a GP IIb/IIIa for patients with renal insufficiency resulting in excessive dosing of GP IIb/IIIa inhibitors increases the risk of major bleeding and is particularly common among the elderly, women, and patients with renal insufficiency. The ACUITY study suggests that bivalirudin plus a GP IIb/IIIa inhibitor is a suitable alternative to standard therapy for moderate- to high-risk patients with non-ST-segment elevation ACS who are undergoing early invasive intervention, and bivalirudin alone may be preferred because of a lower risk of major bleeding. However, interpretation of the ACUITY results is complicated by numerous methodologic concerns, so the role of bivalirudin in managing non-ST-segment elevation ACS is still evolving. In patients with ST-segment elevation, clopidogrel provides an early benefit in reopening occluded coronary arteries and a late benefit in reducing cardiovascular mortality and morbidity without increasing the risk of bleeding. Clopidogrel treatment is warranted before as well as after percutaneous coronary intervention in patients with ST-segment elevation MI who receive fibrinolytic therapy. Adding clopidogrel to fibrinolytic therapy and other standard therapy reduces mortality without increasing the risk of bleeding.. Evidence-based guidelines provide recommendations for the management of ACS, but the pace of clinical research is rapid and current guidelines do not reflect the latest research findings. Pharmacists need to stay abreast of new developments and ensure that clinical practice reflects these developments.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Clinical Protocols; Clopidogrel; Coronary Disease; Drug Administration Schedule; Drug Therapy, Combination; Evidence-Based Medicine; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Recombinant Proteins; Ticlopidine

The Clinical Trials described in this article were presented at the Hotline and Clinical Trial Update Sessions of the European Society of Cardiology Congress held in September 2007 in Vienna, Austria. The sessions chosen for this article represent the scope of interest of Cardiovascular Drugs and Therapy. The presentations should be considered preliminary, as further analyses could alter the final publication of the results of these studies. PROSPECT evaluated echocardiographic criteria for optimal selection of patients with moderate to severe heart failure who may benefit from cardiac resynchronisation therapy, however concluded that no single echocardiographic measure can be recommended. EVEREST found that tolvaptan, a vasopressin V(2) antagonist, resulted in early weight reduction and improvement of dyspnoea in patients with acute heart failure, but lacked long term improvement. In ARISE, the anti-oxidant succinobucal did not affect the primary outcome in high risk cardiovascular patients, but improved the combination of cardiovascular death, myocardial infarction and stroke, and diabetic control in diabetics. ALOFT showed that the addition of the renin inhibitor aliskiren to an ACE inhibitor or ARB and a beta-blocker leads to favourable effects on neurohormonal actions in heart failure. FINESSE markedly improved coronary patency before PCI with half-dose reteplase/abciximab in STEMI patients, however without significantly improving short-term outcome. The Prague-8 Study evaluated whether routine clopidogrel administered >6 h pre-angiography would be a safe way to achieve therapeutic drug levels in case a follow-up intervention would be considered immediately, but appeared not justified because of bleeding complications. CARESS in MI showed that high risk patients with evolving STEMI who undergo thrombolytic therapy should undergo PCI early after the thrombolysis. Finally, the ACUITY trial found that in moderate or high risk Non ST elevation ACS patients triaged to PCI, coronary artery bypass graft (CABG) surgery, or medical management, bivalirudin, with or without associated GPIIb/IIIa inhibitor therapy, resulted in a marked reduction of bleeding at 30 days whilst preserving the ischemic and mortality benefit at 1 year follow up.

Topics: Abciximab; Acute Coronary Syndrome; Amides; Antibodies, Monoclonal; Benzazepines; Clinical Trials as Topic; Clopidogrel; Electrocardiography; Europe; Fumarates; Heart Diseases; Heart Failure; Hirudins; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Peptide Fragments; Probucol; Recombinant Proteins; Ticlopidine; Tolvaptan

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Drug Administration Schedule; Drug Therapy, Combination; Endothelium, Vascular; Enoxaparin; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombophilia

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

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Circulation; Eptifibatide; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins

The REPLACE-2 trial demonstrated that bivalirudin with provisional glycoprotein IIb/IIIa (GPIIb/IIIa) inhibition is not inferior to heparin plus GPIIb/IIIa inhibition in patients undergoing percutaneous coronary intervention. The extent to which this applies to patients with acute coronary syndromes (ACS) is unclear. Therefore, we sought to determine if bivalirudin has similar efficacy in ACS patients as compared with "stable" patients in the REPLACE-2 trial.. We analyzed the outcomes of ACS patients compared with stable patients and the outcomes of ACS patients according to whether or not they had received bivalirudin, including the economic costs. The trial enrolled 1351 ACS patients (myocardial infarction within 7 days or unstable angina within 48 hours, but not on ongoing GPIIb/IIIa or heparin therapy) and 4554 stable patients.. Patients with ACS had a similar rate of death or myocardial infarction at 30 days compared to stable patients (7.2% vs 6.7%, P = .51) and death at 1 year (1.6% vs 2.2%, P = .169), but a higher rate of urgent coronary artery bypass graft at 30 days (1.0% vs 0.3%, P = .002). Patients with ACS treated with bivalirudin had a similar rate of 30-day death, myocardial infarction, or urgent revascularization compared with ACS patients treated with heparin and GPIIb/IIIa inhibitors (8.7% vs 8.0%, P = .616) and death at 1 year (1.5% vs 1.8%, P = .701), but a higher rate of revascularization at 6 months (12% vs 8.4%, P = .04). Patients with ACS treated with bivalirudin had less major bleeding than ACS patients treated with heparin and GPIIb/IIIa inhibitors, although this was not statistically significant (2.7% vs 4.5%, P = .07). Mean 30-day costs for patients with ACS were dollar 12415 for those treated with bivalirudin and dollar 12806 for those treated with heparin plus GPIIb/IIIa inhibitors (P = .022).. Bivalirudin with provisional GPIIb/IIIa inhibitor use in low-risk ACS patients (not receiving preprocedural GPIIb/IIIa blockade) appears to provide similar protection against death and myocardial infarction as the combination of heparin and GPIIb/IIIa inhibitors, although we observed a higher rate of revascularization at 6 months.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Combined Modality Therapy; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Syndrome; Treatment Outcome; United States

Patients with an acute anterior ST-segment elevation myocardial infarction and right bundle-branch block (RBBB) have a high mortality risk, which may be stratified by early ECG changes.. In the Hirulog Early Reperfusion Occlusion (HERO-2) trial, 17 073 patients with acute myocardial infarction (AMI) within 6 hours of symptom onset were treated with streptokinase and randomized to receive bivalirudin or heparin. There was no difference in the primary end point of 30-day mortality. ECGs were recorded at randomization and 60 minutes after fibrinolytic therapy was begun. The 30-day mortality rate was 31.6% in the 415 patients with RBBB and anterior AMI at randomization and 33% in the 100 patients who developed new RBBB at 60 minutes from normal baseline conduction accompanying an anterior AMI. An increase in QRS duration by 20-ms increments was associated with increasing 30-day mortality rate in both RBBB groups on multivariable analyses with covariates of age, Killip class, systolic blood pressure, pulse, and prior infarction. Patients with QRS duration > or = 160 ms had higher 30-day mortality rate than those with QRS duration < 160 ms (37.2% versus 27.2%, P = 0.03, and 46.2% versus 24.5%, P = 0.025, in the 2 groups, respectively). For the patients with RBBB and anterior MI at randomization, RBBB resolved at 60 minutes in 40 patients, but 30-day mortality rate was unchanged. For those with persisting RBBB at 60 minutes, 30-day mortality rate was lower if ST-segment elevation had resolved by > or = 50% (20.4% versus 35.3%, P = 0.006).. In patients with anterior AMI and RBBB, increasing QRS duration is associated with increasing 30-day mortality. Early ST-segment resolution after fibrinolytic therapy despite persisting RBBB is associated with lower mortality rate.

Topics: Aged; Anticoagulants; Bundle-Branch Block; Cardiovascular Diseases; Electrocardiography; Female; Fibrinolytic Agents; Functional Laterality; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Streptokinase; Survival Analysis

Heparin with adjunctive glycoprotein IIb/IIIa platelet receptor (GP IIb/IIIa) inhibitors has demonstrated its effectiveness in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Bivalirudin, a direct thrombin inhibitor, has recently been shown to be an effective alternative for patients undergoing elective PCI.. To assess the angiographic and clinical outcomes of adjunctive pharmacological strategies in a high-risk population presenting with ACS.. Of 891 consecutive PCI patients with ACS, 304 received bivalirudin (60.5% male, 68+/-11 years) and were compared with 283 who received heparin (58.7% male, 66+/-12 years). A 30-day major adverse cardiac event was defined as the occurrence of cardiac death, nonfatal myocardial infarction, urgent revascularization or major hemorrhage.. Adjunctive GP IIb/IIIa inhibitors were used in 14.1% of the bivalirudin group and in 72.4% of the heparin group (P<0.010). The occurrence of Thrombolysis In Myocardial Infarction (TIMI) flow less than grade 3 was lower and the achievement of angiographic success was higher in the bivalirudin group than in the heparin group (5.2% versus 8.2%, 94.7% versus 89.7%, P=0.039 and P<0.010, respectively). There was no difference between groups in the incidence of bleeding events (bivalirudin 2.0% versus heparin 3.5%, P not significant) and in 30-day major adverse cardiac events (bivalirudin 8.3% versus heparin 5.7%, P=0.223).. In the high-risk cohort undergoing PCI, bivalirudin with provisional GP IIb/IIIa inhibitors achieved better angiographic results. Although not powered to show a difference, and while acknowledging that a selection bias could have affected the data, the present study showed that bivalirudin may be as clinically effective and safe as heparin with adjunctive GP IIb/IIIa inhibitors.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Disease; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Syndrome; Treatment Outcome

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

The purpose of this research was to examine the prognostic value of ST-segment changes (concordant ST-segment elevation and/or precordial V1 to V3 ST-segment depression) during presumed-new left bundle branch block (LBBB) in patients receiving fibrinolytic therapy.. These patients are often considered high-risk, but their outcome is not well-defined.. The Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial compared bivalirudin with heparin in patients receiving streptokinase for ST-segment elevation or presumed-new LBBB. Each patient with LBBB was matched with a control (with normal intraventricular conduction) for age, gender, pulse rate, systolic blood pressure, Killip class, and region.. A total of 300 patients had LBBB (92 with and 208 without ST-segment changes) and 15,340 had normal conduction. Acute myocardial infarction (AMI) occurred in 80.7% of LBBB patients and 88.7% of controls (p = 0.006). ST-segment changes were specific (96.6%) but not sensitive (37.8%) for enzymatic diagnosis of AMI. Mortality at 30 days was similar in LBBB patients with ST-segment changes (21.7%) and controls (25.0%, p = 0.563), but lower in LBBB patients without ST-segment changes than in controls (13.5% vs. 21.6%, p = 0.022). In the whole HERO-2 cohort, the LBBB patients with ST-segment changes had higher mortality than patients with normal conduction (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.78 to 2.42). The LBBB patients without ST-segment changes had lower mortality than patients with normal conduction (OR 0.52, 95% CI 0.33 to 0.80).. ST-segment changes during LBBB are specific for the diagnosis of AMI and predict 30-day mortality; LBBB patients without ST-segment changes have lower adjusted 30-day mortality than those with normal conduction. Trials are required to determine the best treatment for high-risk and low-risk patients with LBBB.

Topics: Aged; Angina Pectoris; Anticoagulants; Bundle-Branch Block; Electrocardiography; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Predictive Value of Tests; Recombinant Proteins; Streptokinase; Survival Rate; Time Factors

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Arthroplasty, Replacement, Knee; Cardiac Catheterization; Drug Delivery Systems; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Postoperative Care; Recombinant Proteins; Stents

The objective of this retrospective analysis of high-risk patients treated with bivalirudin during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) was to evaluate the safety and feasibility of direct thrombin inhibitor (DTI) without concomitant glycoprotein (GP) IIb/IIIa inhibition.. Reperfusion by PCI is the treatment of choice for patients with STEMI. In patients with stable or unstable angina without ST-segment elevation undergoing PCI, bivalirudin was at least as effective as heparin plus GPIIb/IIIa inhibitors in reducing ischemic events and more effective in preventing bleeding. There are no published studies detailing the use of bivalirudin in patients with STEMI.. From 09/02 to 05/03 at the Heart Care Centers of Illinois, Blue Island, Illinois. Ninety-one consecutive patients with STEMI underwent PCI with or without stent placement. Bivalirudin was administered as a bolus dose (0.75 mg/kg) followed by infusion (1.75 mg/kg/hr) for the duration of the procedure. Outcomes were recorded over a 30-day follow-up period.. Patients (n = 91) had several high-risk characteristics (40% female, 30% diabetes mellitus, 21% previous MI and 18% cardiogenic shock). PCI procedures utilized balloons, stents, or a combination of both. Intraaortic balloon pumps were used for 41% and closure devices for 24% of patients.. This evaluation demonstrates excellent TIMI flow without the addition of GPIIb/IIIa inhibitors. The low mortality and complication rates suggest anticoagulation with bivalirudin in patients with STEMI undergoing PCI is feasible and warrants further study in larger controlled trials to evaluate the effectiveness of bivalirudin in this patient population.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Female; Follow-Up Studies; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Up to 5% of patients given heparin develop heparin-induced thrombocytopenia (HIT). These patients may need anticoagulation for acute coronary syndromes (ACS) or percutaneous coronary intervention (PCI), a clinical challenge given the limited alternatives. In a prospective, open-label study, we evaluated the safety and efficacy of bivalirudin in patients with HIT or HIT with thrombotic syndrome (HITTS) undergoing PCI. Patients aged 18 years were enrolled in 24 centers in 2 countries. Bivalirudin was given 5 minutes before PCI (1 mg/kg bolus; 2.5 mg/kg/hour infusion for 4 hours [high-dose group] or 0.75 mg/kg bolus; 1.75 mg/kg/hour infusion [low-dose group]). Clinical and hematological measures were assessed within 24 hours after starting bivalirudin, just before PCI, just before sheath removal, and 48 hours after treatment or at discharge, whichever occurred first. The primary endpoint was major bleeding 48 hours after discontinuation or until discharge, whichever occurred first. From July 1999 to February 2003, 52 patients were recruited. Procedural success (TIMI grade 3 flow and < 50% stenosis) was achieved in 98% of patients, and clinical success (absence of death, emergency bypass surgery, or Q-wave infarction) was achieved in 96%. One high-dose patient who underwent elective bypass surgery had major bleeding (1.9%; 95% CI: 0.05 10.65%), and 7 patients had minor bleeding. No patient had significant thrombocytopenia (platelet count < 50 109/L) after treatment. One patient in the low-dose group died from cardiac arrest ~46 hours after uncomplicated PCI. Bivalirudin appeared safe and provided effective anticoagulation during PCI. These data, and extensive experience with bivalirudin in PCI, support its use in high-risk patients with HIT requiring PCI.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Prospective Studies; Recombinant Proteins; Thrombocytopenia; Treatment Outcome

Topics: Adult; Angioplasty, Balloon, Coronary; Antithrombins; Cardiac Catheterization; Coronary Circulation; Coronary Stenosis; Hirudins; Humans; Intraoperative Care; Male; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

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: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Reproducibility of Results

Despite advances in percutaneous coronary intervention (PCI) techniques and adjunctive therapies, the risks of ischemic and bleeding complications with PCI remain significant. These complications are associated with significant morbidity and mortality, as well as substantially higher costs. Bivalirudin is the only antithrombotic agent that has been shown to reduce both ischemic and hemorrhagic complications associated with PCI. Cost models drawn from the results of three clinical trials of bivalirudin have estimated its potential impact on total medical costs. In addition, the number needed to treat to avoid a bleeding complication has been calculated based on patients shown to have a heightened risk of bleeding in the Bivalirudin Angioplasty Trial. In all models assessed, the use of bivalirudin offset most of its own cost through reductions in bleeding and ischemic complications.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Blood Transfusion; Costs and Cost Analysis; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Insufficiency; Reoperation

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Clinical Trials as Topic; Coronary Disease; Cost-Benefit Analysis; Data Interpretation, Statistical; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Odds Ratio; Peptide Fragments; Radiography; Recombinant Proteins; Recurrence; Research Design; Treatment Outcome

This study was a reanalysis of the Bivalirudin Angioplasty Study, which compared bivalirudin with high-dose heparin during coronary angioplasty for unstable angina.. Differences in rates of death, myocardial infarction, or repeat revascularization were compared at 7, 90, and 180 days after angioplasty with intention-to-treat analysis.. The combined end point occurred in 135 of 2161 patients (6.2%) in the bivalirudin group and in 169 of 2151 patients (7.9%) in the heparin group at 7 days (P =.039). Differences persisted between the groups at 90 days (P =.012) and 180 days (P =.153). Bleeding occurred in 76 patients (3.5%) in the bivalirudin group versus 199 (9.3%) in the heparin group (P <.001).. This analysis supports the hypothesis that bivalirudin reduces ischemic complications and bleeding after angioplasty. Further trials are needed to evaluate bivalirudin versus heparin in conjunction with platelet-glycoprotein IIb/IIIa inhibitors and for coronary stenting.

Topics: Actuarial Analysis; Adult; Aged; Aged, 80 and over; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Aspirin; Female; Follow-Up Studies; Heparin; Hirudin Therapy; Hirudins; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate

Topics: Animals; Antithrombins; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Swine; Thrombolytic Therapy

A brief outline is presented of a proposed trial of Hirulog versus heparin after thrombolytic therapy with streptokinase (SK). The lower patency rates achieved with SK compared with tissue plasminogen activator (t-PA) suggest that a potent thrombin specific agent may be more important for SK than for t-PA therapy. This study will involve more than 400 patients with two dose levels of Hirulog. Endpoints will be angiographic patency, and ST segment monitoring showing evidence of coronary reperfusion.

Topics: Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Streptokinase; Thrombin; Thrombolytic Therapy; Vascular Patency