bivalirudin and Coronary-Thrombosis

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

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

To evaluate the efficacy of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion (at full PCI dose) to prevent stent thrombosis (ST) compared with heparin monotherapy.. Early randomized controlled trials (RCTs) have shown that compared with heparin use, bivalirudin use during primary PCI is associated with an increased risk of ST. However, bivalirudin was stopped in those trials at the end of the procedure and glycoprotein IIb/IIIa inhibitors (GPIs) were routinely used with heparin. The increased risk of ST may be eliminated by continuing bivalirudin infusion post-procedure for few hours. Indeed, in most recent trials, a trend of lower ST risk has been observed with a post-procedure infusion of bivalirudin compared with heparin monotherapy (without the routine use of GPI).. Relevant RCTs were included and risk ratios (RRs) were calculated using random effect models. The primary outcome of interest was the risk of early definite ST.. Four RCTs involving 13,505 patients were included in this meta-analysis. Compared with heparin monotherapy, bivalirudin (with a post-procedure infusion) was associated with a 55% decrease in the risk of early definite ST (RR: 0.45, 95% confidence interval: 0.23-0.85; P = 0.015). There was no difference in the risk of early ST between bivalirudin (with a post-procedure infusion) and heparin with GPI.. For primary PCI, a bivalirudin-based anticoagulant strategy (with post procedure infusion) is associated with a lower risk of early definite ST compared with treatment with heparin monotherapy (without GPI).

Topics: Anticoagulants; Antithrombins; Coronary Artery Disease; Coronary Thrombosis; Drug Administration Schedule; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Stents; Time Factors; Treatment Outcome

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

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

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

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

The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI).. Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI.. Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods.. A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor.. In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents.

Topics: Adenosine; Antithrombins; Bayes Theorem; Blood Platelets; Clinical Trials as Topic; Clopidogrel; Coronary Thrombosis; Drug-Eluting Stents; Evidence-Based Medicine; Hirudins; Humans; Markov Chains; Monte Carlo Method; Network Meta-Analysis; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Recombinant Proteins; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Treatment Outcome

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

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

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

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

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

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

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

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 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

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Coronary Thrombosis; Endothelium, Vascular; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Activation; Polysaccharides; Postoperative Complications; Recombinant Proteins; Thrombin

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

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

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

Topics: Angioplasty, Balloon, Coronary; Arginine; Coronary Thrombosis; Drug Therapy, Combination; Fibrinolytic Agents; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Sulfonamides

Much progress has been made in understanding and treating acute coronary syndromes. For patients undergoing percutaneous transluminal coronary angioplasty, anticoagulant therapy during the procedure must strike a balance between providing sufficient anticoagulation to prevent thrombus formation and ischemic complications while averting hemorrhagic complications. Bivalirudin, a thrombin-specific anticoagulant, is the only anticoagulant that reduces both ischemic and bleeding complications associated with percutaneous coronary intervention (PCI). Bivalirudin is easy to use, provides predictable anticoagulation, inactivates both free and clot-bound thrombin, and blocks thrombin-mediated platelet activation and aggregation. Drug-drug interaction studies have found no clinically relevant interactions between bivalirudin and ticlopidine, abciximab, tirofiban, or eptifibatide. Bivalirudin is well tolerated by patients who previously received low-molecular-weight heparin (LMWH), when LMWH is discontinued 8-14 hours before bivalirudin is started. Similarly, switching from heparin to bivalirudin at the time of PCI reduces both ischemic and bleeding events.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Coronary Thrombosis; Drug Interactions; Fibrinolytic Agents; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins; Thrombocytopenia; Ticlopidine

Acute coronary syndromes encompass a spectrum of conditions, including myocardial infarction and unstable angina. These syndromes are related to the formation and disruption of atherosclerotic plaque. Rupture of plaque leads to thrombin generation, fibrin deposition, and platelet aggregation, ultimately resulting in restriction of blood flow and ischemia of cardiac tissue. Percutaneous coronary intervention (PCI), including angioplasty and coronary stent placement, has been developed to open occluded arteries. The frequency with which these procedures are performed speaks to their largely successful outcomes. However, the mechanical manipulations of PCI result in additional plaque rupture and damage to the vessel wall, exposing subendothelial components to blood and resulting in the initiation of the clotting cascade and in platelet activation. Left unchecked, these intertwined processes lead to formation of arterial thrombi at the site of endothelial damage, and potentially to abrupt vessel closure or embolization of thrombi into the distal microcirculation. Thrombin plays a central role in thrombus formation and platelet activation, and its inhibition significantly reduces thrombus-related sequelae. Current antithrombotic strategies during PCI are based on the traditional indirect thrombin inhibitor heparin. Heparin has several limitations in efficacy and safety, due in part to its indirect mechanism of action. Bivalirudin, a direct thrombin inhibitor, offers significant improvement over heparin in the clinical outcomes and risks associated with PCI.

Topics: Angioplasty, Balloon, Coronary; Arginine; Clinical Trials as Topic; Coronary Disease; Coronary Thrombosis; Fibrinolytic Agents; Fondaparinux; Heparin; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombin

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Blood Coagulation; Clinical Trials as Topic; Coronary Thrombosis; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Coronary Thrombosis; Hirudins; Humans; Incidence; Infusions, Intravenous; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Safety; Survival Rate

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Thrombosis; Heparin; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Safety; Thrombocytopenia; Treatment Outcome

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

Given the central role of thrombin in arterial thrombogenesis, most treatment strategies for acute coronary syndromes are aimed at inhibiting its generation or blocking its activity. Although heparin has been widely used, it has limitations in the setting of arterial thrombosis. These limitations reflect the inability of heparin to inactivate thrombin bound to fibrin, a major stimulus for thrombus growth. In addition, the anticoagulant response to heparin varies from patient to patient, and heparin is neutralized by platelet Factor IV, large quantities of which are released from platelets activated at sites of plaque rupture. Consequently, heparin requires careful laboratory monitoring to ensure an adequate anticoagulant effect. Direct thrombin inhibitors, such as hirudin and bivalirudin, overcome the limitations of heparin. These agents inhibit fibrin-bound thrombin, as well as fluid-phase thrombin, and produce a predictable anticoagulant response. Bivalirudin has both safety and potential efficacy advantages over hirudin. Bivalirudin appears to have a wider therapeutic window than hirudin, possibly because bivalirudin only transiently inhibits the active site of thrombin. The better safety profile of bivalirudin permits administration of higher doses, which may give it an efficacy advantage. Hirudin prevents thrombin from activating protein C, thereby suppressing this natural anticoagulant pathway. In contrast, bivalirudin may promote protein C activation by transiently inhibiting thrombin until it can be bound by thrombomodulin. Differences between bivalirudin and hirudin, as well as other direct thrombin inhibitors, highlight the pitfalls of considering all direct thrombin inhibitors to have equivalent risk-benefit profiles.

Topics: Acute Disease; Antithrombins; Coronary Thrombosis; Drug Monitoring; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Protein C; Recombinant Proteins

The initiating event in unstable angina is plaque rupture. It triggers platelet activation and aggregation, leading to the formation of an intracoronary thrombus, which can be detected on autopsy, angiography, and by fiber-optic coronary angioscopy. Biochemical markers of platelet and thrombin activity are usually increased and support the pathophysiologic role of coronary thrombosis in unstable angina. Aspirin and heparin have been shown to be effective, whereas thrombolytic therapy has no beneficial clinical effect. Newer specific antithrombotic drugs (hirudin, hirulog) and GPIIb/IIIa platelet receptor inhibitors are being tested in clinical trials and seem to provide a new dimension for the treatment of acute coronary syndromes.

Topics: Angina, Unstable; Blood Coagulation Disorders; Coronary Thrombosis; Heparin; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Recombinant Proteins; Thrombin

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

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

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

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

Topics: Antithrombins; Coronary Thrombosis; Drug Administration Schedule; Hirudins; Humans; Infusions, Parenteral; Peptide Fragments; Percutaneous Coronary Intervention; Predictive Value of Tests; Recombinant Proteins; ST Elevation Myocardial Infarction; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

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

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

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

Many sites routinely continue anticoagulation after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI), despite an unclear benefit-risk ratio. We evaluated the impact of this strategy on 30-day outcomes from a pooled patient-level database of two large primary percutaneous coronary intervention trials.. EUROMAX and HORIZONS-AMI were both multicentre, international randomised trials comparing bivalirudin to heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary percutaneous coronary intervention. Outcomes at 30 days were analysed according to the use of post-procedural anticoagulation (unfractionated or low-molecular-weight heparins or fondaparinux) outside of the catheterisation laboratory.. Among 5239 patients undergoing primary percutaneous coronary intervention, 2153 (41.1%) received post-procedural anticoagulation. After adjusting for differences in baseline variables, there were no differences in the 30-day rates of adverse ischaemic events between patients without versus with post-procedural anticoagulation: adjusted odds ratio for major adverse cardiac events 0.80; 95% confidence interval 0.60-1.07; P=0.14; adjusted odds ratio for stent thrombosis 0.82; 95% confidence interval 0.55-1.24; P=0.35; adjusted odds ratio for death 1.07; 95% confidence interval 0.69-1.66; P=0.77. Conversely, protocol-defined major bleeding was decreased without post-procedural anticoagulation: adjusted odds ratio 0.74; 95% confidence interval 0.58-0.94; P=0.01. Similar results were observed for Thrombolysis In Myocardial Infarction major and minor bleeding.. In this large STEMI database, a substantial proportion of primary percutaneous coronary intervention patients received post-procedural anticoagulation, which in turn was associated with higher bleeding rates without any reduction in ischaemic events. Therefore, routine post-procedural anticoagulation after primary percutaneous coronary intervention seems to have an unfavourable benefit-risk profile and should be avoided unless a well-established indication is present.. ClinicalTrials.gov , EUROMAX Identifier NCT01087723; HORIZONS Identifier NCT00433966.

Topics: Aged; Antithrombins; Coronary Angiography; Coronary Thrombosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Care; Recombinant Proteins; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Treatment Outcome

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

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

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

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

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

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

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

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

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

We investigated whether bivalirudin is more effective than heparin in preventing ischemic complications in high risk patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography.. Heparin is administered during coronary angioplasty to prevent closure of the dilated vessel. Bivalirudin (Hirulog) is a direct thrombin inhibitor that can be safely substituted for heparin during angioplasty. Bivalirudin has several theoretic advantages over heparin as an anticoagulant agent.. We performed an observational analysis of the Hirulog Angioplasty Study in which 4,098 patients with unstable or postinfarction angina were randomized to receive either bivalirudin or heparin during coronary angioplasty. The study group for this analysis consisted of 567 patients who had thrombus-containing lesions on angiography. The primary end point was death, myocardial infarction, emergency coronary artery bypass graft surgery or abrupt vessel closure before hospital discharge.. Patients with thrombus-containing lesions had a higher incidence of myocardial infarction (5.1% vs. 3.2%, p = 0.03) and abrupt vessel closure (13.6% vs. 8.3%, p < 0.001) than those without thrombus. In patients with thrombus-containing lesions, however, the incidence of the primary end point was not different between the bivalirudin and heparin treatment groups. Furthermore, no difference in the incidence of ischemic events at 6 months was seen between the treatment groups.. Bivalirudin is not more effective than heparin in preventing ischemic complications in patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography. Other approaches, perhaps involving potent anti-platelet agents, should be considered for patients with thrombus-containing lesions.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Thrombosis; Double-Blind Method; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Ischemia; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

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

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

An 81-year-old woman presented with acute decompensated heart failure due to new-onset atrial fibrillation and a flail myxomatous mitral valve which necessitated surgical mitral valve repair. No atrial thrombi were noted on transoesophageal echocardiograms performed prior to surgery and intraoperatively. Immediately postoperatively, while treated with unfractionated heparin, the patient developed thrombocytopaenia with positive platelet factor 4 antibodies and an abnormal serotonin functional platelet assay, consistent with heparin-induced thrombocytopaenia. The anticoagulation therapy was changed to the direct thrombin inhibitor bivalirudin with an improvement in the platelet count. Despite bivalirudin therapy, a left atrial layering thrombus was revealed on transoesophageal echocardiogram performed in preparation for cardioversion of the symptomatic atrial fibrillation. Anticoagulation was changed to warfarin, and the patient was discharged without thromboembolic complications neither during her hospital stay nor the 3-year outpatient follow-up.

Topics: Aged, 80 and over; Anticoagulants; Antithrombins; Coronary Thrombosis; Echocardiography, Transesophageal; Female; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombocytopenia; Warfarin

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

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

Thrombus formation after stent deployment has been linked to the use of heparin and of antithrombotic agents, such as bivalirudin, during percutaneous coronary intervention. Fluoroscopy has been used to identify stent thrombosis, typically after patients become symptomatic. We describe our use of optical coherence tomography to diagnose and evaluate intraprocedural stent thrombosis in a 68-year-old man who was given bivalirudin just before a percutaneous coronary procedure. This imaging method enabled immediate therapeutic intervention.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antithrombins; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Peptide Fragments; Platelet Aggregation Inhibitors; Predictive Value of Tests; Recombinant Proteins; Stents; Tomography, Optical Coherence; Treatment Outcome

Aspiration thrombectomy was performed to retrieve intact thrombus in a 69-year-old woman. Bradycardia and hypotension rapidly resolved. Balloon angioplasty was performed at the site of proximal RCA in-stent restenosis with improved angiographic appearance and TIMI 3 flow in the major branches.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Electrocardiography; Female; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; ST Elevation Myocardial Infarction; Syncope; Treatment Outcome

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

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

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

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

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

This study aimed to compare the effect of bivalirudin and unfractionated heparin (UFH) on residual thrombus burden assessed by frequency-domain optical coherence tomography (FD-OCT), and on angiographic indices of microvascular obstruction (MVO).. The efficacy of bivalirudin to inhibit thrombus formation inside the stent during percutaneous coronary interventions (PCI) as compared to UFH is unknown.. Sixty patients with coronary artery disease who underwent post-PCI FD-OCT were studied, including 20 patients treated with bivalirudin and 40 control patients treated with UFH, matched by clinical presentation, stent characteristics, and periprocedural medications. In-stent thrombus volume, thrombus score (number of quadrants with thrombus), and thrombus type (white/red) were assessed by FD-OCT. Thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and Quantitative Blush Evaluator (QuBE) score were recorded.. Patients treated with bivalirudin showed similar thrombus volume (0.14 mm(3) [0.00-0.88] vs. 0.13 mm(3) [0.00-0.63], P = 0.962), thrombus score (10 [0-25] vs. 8 [0-21], P = 0.849) and thrombus length (1.70 mm [0.00-4.10] vs. 1.40 mm [0.00-4.05], P = 0.968], as compared with patients treated with UFH. Patients in the bivalirudin group showed lower proportion of white thrombus (55.5% vs. 78.6%, P = 0.016). There was no significant difference in TIMI flow grade, cTFC, and QuBE score between the two groups.. The present study showed similar residual thrombus burden and angiographic indices of MVO immediately after PCI between patients treated with bivalirudin and those treated with UFH.

Topics: Aged; Controlled Clinical Trials as Topic; Coronary Angiography; Coronary Artery Disease; Coronary Circulation; Coronary Thrombosis; Coronary Vessels; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Microcirculation; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Predictive Value of Tests; Recombinant Proteins; Registries; Retrospective Studies; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To evaluate the clinical, angiographic, and cardiac magnetic resonance imaging (cMRI) results in patients with and without diabetes mellitus (DM) undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).. DM has been associated with increased mortality in patients with STEMI, yet the mechanisms underpinning this association have not been completely elucidated.. Overall, 451 patients (51 diabetics) from the INFUSE-AMI trial were studied. They presented with an anterior STEMI due to an occluded left anterior descending artery (LAD) and underwent bivalirudin-supported primary PCI with or without intralesion abciximab and with or without thrombus aspiration. Angiographic baseline and post-procedure parameters, cMRI at 30 days, and clinical follow-up at 30 days and at 1 year were compared between diabetic and nondiabetic patients.. Patients with DM had significantly more comorbidities and more extensive LAD disease than nondiabetics. Primary PCI was equally effective in restoring coronary flow in both groups and the infarct size at 30 days was similar (14.3% [7.1, 24.5] vs. 17.3% [8.1, 23.6], respectively, P = 0.55). Diabetic patients had more major cardiovascular and cerebrovascular events at 1 year (16.5% vs. 8.0%, P = 0.04). Stent thrombosis within 30 days after primary PCI was higher in diabetic than in nondiabetic subjects (4.3% vs. 0.8%, P = 0.03).. Patients with DM presenting with STEMI had a higher baseline risk profile than those without DM. Although reperfusion success and infarct size were similar, diabetic patients experienced more death, reinfarction, stent thrombosis, and revascularization than nondiabetics.

Topics: Abciximab; Aged; Anterior Wall Myocardial Infarction; Antibodies, Monoclonal; Antithrombins; Cerebrovascular Disorders; Coronary Angiography; Coronary Thrombosis; Diabetes Complications; Female; Hirudins; Humans; Immunoglobulin Fab Fragments; Magnetic Resonance Imaging; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Suction; Time Factors; 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

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

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

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

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

Topics: Acute Disease; Aged; Antithrombins; Clopidogrel; Coronary Thrombosis; Drug-Eluting Stents; Eptifibatide; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Factors; Ticlopidine; Tomography, Optical Coherence

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

Patients that receive coronary bare-metal or drug-eluting stents have to be maintained on dual antiplatelet therapy (DAPT) for at least 4 weeks or 12 months, respectively. The prolonged time period required for drug-eluting stents is the result of delayed vascular healing that is associated with the drug and the polymeric coating. Premature cessation of DAPT may precipitate life-threatening stent thrombosis. However, some urgent, unplanned surgical procedures cannot be carried out under DAPT as a result of an unacceptable bleeding risk. Therefore, in these particular patients, DAPT therapy needs to be bridged for urgent surgery to avoid stent thrombosis, yet no clinical recommendation about a specific pharmacologic protocol is currently available for this specific purpose. We report about the initial experience with a novel institutional bridging protocol using bivalirudin that has been developed and applied successfully in a limited number of patients.

Topics: Antithrombins; Aspirin; Blood Loss, Surgical; Clopidogrel; Coronary Thrombosis; Drug-Eluting Stents; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Recombinant Proteins; Stents; Surgical Procedures, Operative; Ticlopidine; Time 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

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

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

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

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

Percutaneous coronary intervention (PCI) is routinely performed in patients with non-ST elevation acute coronary syndromes after pretreatment with clopidogrel and periprocedural administration of unfractionated heparin on a weight-adjusted basis. Although activated clotting time (ACT) monitoring is encouraged to verify the adequacy of anticoagulation during the procedures, this is not a common practice in many laboratories. The authors describe 4 cases of patients with bifurcation lesions involving the left anterior descending coronary artery, who developed periprocedural thrombosis with acute transmural ischemia. All patients had inadequate ACT measurements, despite conventional heparin dosage and ongoing clopidogrel treatment. In order to achieve complete anticoagulation, patients were switched to bivalirudin, which determined a prompt effect on measured ACT. This therapeutic regimen, coupled with further intervention, allowed resolution of the thrombotic complication without bleeding. This report suggests the feasibility of a strategy of bivalirudin use in patients who have some degree of heparin 'resistance' in the setting of complicated PCI.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Thrombosis; Female; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; 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

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

Topics: Adult; Antithrombins; Cocaine; Cocaine-Related Disorders; Coronary Thrombosis; Electrocardiography; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Treatment Outcome; Vasoconstrictor Agents

Bivalirudin is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. Cases of intracoronary thrombosis have been reported with beta-radiation when bivalirudin is used as an anticoagulant. We report two cases of intracoronary thrombosis with gamma-radiation when bivalirudin is used.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Antithrombins; Brachytherapy; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Female; Gamma Rays; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Swine

Topics: Anticoagulants; Antithrombins; Cardiovascular Surgical Procedures; Combined Modality Therapy; Coronary Thrombosis; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Treatment Outcome

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

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

Heparin-associated thrombocytopenia is a serious medical problem, especially when the patient requires continued anticoagulation. Hirulog is an immediate-acting intravenous anticoagulant that can be substituted for heparin. A new use of Hirulog in the treatment of life-threatening heparin-associated thrombocytopenia with thrombosis (HATT) is presented. Two patients suffering from the HATT syndrome were successfully treated with Hirulog to prevent further thrombosis. A third patient had developed heparin-associated thrombocytopenia after coronary artery bypass surgery in the past and was subsequently treated with Hirulog during a peripheral angioplasty procedure. Hirulog was an effective and predictable anticoagulant for these patients and was free from adverse effects.

Topics: Aged; Angioplasty, Balloon; Anticoagulants; Coronary Artery Bypass; Coronary Thrombosis; Heparin; Hirudin Therapy; Hirudins; Humans; Injections, Intravenous; Male; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombin; Thrombocytopenia