bivalirudin and Acute-Coronary-Syndrome

Bivalirudin and heparin are the two most commonly used anticoagulants used during Percutaneous Coronary Intervention (PCI). The results of Randomized Controlled Trials (RCTs) comparing bivalirudin versus heparin monotherapy in the era of radial access are controversial, questioning the positive impact of bivalirudin on bleeding. The purpose of this systematic review is to summarize the results of RCTs comparing the efficacy and safety of bivalirudin versus heparin with or without Glycoprotein IIb/IIIa Inhibitors (GPI).. This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statements for reporting systematic reviews. We searched the National Library of Medicine PubMed, Clinicaltrial.gov and the Cochrane Central Register of Controlled Trials to include clinical studies comparing bivalirudin with heparin in patients undergoing PCI. Sixteen studies met inclusion criteria and were reviewed for the summary.. Several RCTs and meta-analyses have demonstrated the superiority of bivalirudin over heparin plus routine GPI use in terms of preventing bleeding complications but at the expense of increased risk of ischemic complications such as stent thrombosis. The hypothesis of post- PCI bivalirudin infusion to mitigate the risk of acute stent thrombosis has been tested in various RCTs with conflicting results. In comparison, heparin offers the advantage of having a reversible agent, of lower cost and reduced incidence of ischemic complications.. Bivalirudin demonstrates its superiority over heparin plus GPI with better clinical outcomes in terms of less bleeding complications, thus making it as anticoagulation of choice particularly in patients at high risk of bleeding. Further studies are warranted for head to head comparison of bivalirudin to heparin monotherapy to establish an optimal heparin dosing regimen and post-PCI bivalirudin infusion to affirm its beneficial effect in reducing acute stent thrombosis.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Female; Heparin; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Anticoagulant therapy is critical to prevent ischemic recurrences and complications in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Unfractionated heparin (UFH), an injectable anticoagulant has several limitations: lack of predictability of its biological efficacy, platelets activation, heparin-induced thrombopenia and bleedings. Bivalirudin, a synthetic direct thrombin inhibitor has biological properties that promised better clinical outcome in ACS patients undergoing PCI.. The present review aimed to summarize two decades of randomized clinical trials that compared bivalirudin to UFH in ACS patients treated with PCI. Early trials highlighted a reduction of bleedings with bivalirudin compared to UFH in combination with glycoprotein inhibitors (GPI). Recent studies questioned this reduction given that GPI are less and less used during PCI. Further, trials raised concerns about the risk of stent thrombosis in patients treated with bivalirudin. In light of this data, bivalirudin has been downgraded in international guidelines and appears as a second line anticoagulant agent after UFH.. The highly questioned reduction of bleedings under bivalirudin and the potential risk of stent thrombosis are unwarranted. Based on clinical trials, UFH has no equivalent in terms of anticoagulation in ACS patients undergoing PCI.

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

Topics: Acute Coronary Syndrome; Antithrombins; Cardiology; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Poland; Recombinant Proteins; Societies, Medical; Treatment Outcome

Platelets and the coagulation cascade play key roles in initiation, amplification, and perpetuation of acute coronary syndromes (ACS). In the past few years, there has been great progress in ACS antithrombotic treatment with the introduction of novel anticoagulants (fondaparinux and bivalirudin), more potent P2Y

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Aspirin; Blood Coagulation Factors; Fondaparinux; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins

The efficacy and safety of bivalirudin in patients undergoing percutaneous coronary intervention (PCI) for treatment of acute coronary syndromes (ACS) remains controversial despite recent evidence from large randomized-controlled trials (RCTs). Thus, this systematic review and meta-analysis sought to investigate the efficacy and safety of bivalirudin as compared to heparin in patients with ACS undergoing PCI.. Medline/PubMed, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov databases were searched for RCTs. Primary endpoint was MACE consisting of all-cause death, myocardial infarction, and stroke within 30 days. Secondary endpoints were components of the primary endpoint and stent thrombosis. The primary safety endpoint was major bleeding. We identified 12 RCTs comprising 33,844 patients. Between bivalirudin and heparin, there were no significant differences for MACE (OR 1.06; 95% CI 0.96-1.17; p = 0.24), death, myocardial infarction, and stent thrombosis. Similar results were seen following stratification by use of glycoprotein inhibitors (GPI). Major bleeding trended to be less frequent in patients treated with bivalirudin. However, no safety benefit for bivalirudin was seen when use of GPI was balanced between groups (OR 0.88; 95% CI 0.67-1.16; p = 0.35; p for heterogeneity < 0.01).. Compared with heparin, bivalirudin was associated with a similar incidence of ischemic events following PCI for ACS. An association of bivalirudin with decreased bleeding was not seen with balanced use of GPI.

Topics: Acute Coronary Syndrome; Antithrombins; Global Health; Hirudins; Humans; Incidence; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Thrombosis; Treatment Outcome

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

The pathophysiology of acute coronary syndrome (ACS) involves platelet activation and thrombus formation after the rupture of atherosclerotic plaques. Thrombin is generated at the blood-plaque interface in association with cellular membranes on cells and platelets. Thrombin also amplifies the response to the tissue injury, coagulation and platelet response, so the treatment of ACS is based on the combined use of both antiplatelet (such as aspirin, clopidogrel, prasugrel and ticagrelor) and antithrombotic drugs (unfractionated heparin, enoxaparin, fondaparinux and bivalirudin). Bivalirudin competitively inhibits thrombin with high affinity, a predictable response from its linear pharmacokinetics and short action. However, a present remarkable controversy exists between the latest main Guidelines in Clinical Practice and the key trials evaluating the use of bivalirudin in ACS. The aim of this review is to update the development of bivalirudin, including pharmacological properties, obtained information from clinical trials evaluating efficacy and safety of bivalirudin in ACS; as well as the recommendations of clinical Guidelines.

Topics: Acute Coronary Syndrome; Anticoagulants; Clinical Trials as Topic; Drug Therapy, Combination; Female; Hirudins; Humans; Male; Peptide Fragments; Practice Guidelines as Topic; Recombinant Proteins; Thrombin

Contrasting data have been reported on bivalirudin as an anticoagulation strategy during percutaneous coronary interventions, offering theoretical benefits on bleeding complications but raising concerns on a potential increase in the risk of stent thrombosis. We performed an updated meta-analysis to evaluate the efficacy and safety of bivalirudin compared with unfractionated heparin in patients undergoing percutaneous interventions for acute coronary syndromes.. Literature archives and main scientific sessions were scanned. The primary efficacy endpoint was 30-day overall mortality. Secondary endpoints were stent thrombosis and major bleeding. A prespecified analysis was conducted according to clinical presentation.. Twelve randomized trials were included, involving 32 746 patients (52.5% randomized to bivalirudin). Death occurred in 1.8% of the patients, with no differences between bivalirudin and heparin (odds ratio = 0.91; 95% confidence interval, 0.77-1.08; P = .28; P for heterogeneity = .41). Similar results were obtained for patients with non-ST-segment elevation and in ST-segment elevation myocardial infarction. A significantly higher rate of stent thrombosis was observed with bivalirudin (odds ratio = 1.42; 95% confidence interval, 1.09-1.83; P = .008; P for heterogeneity = .09). Bivalirudin was associated with a significant reduction in the rate of major bleeding (odds ratio = 0.60; 95% confidence interval, 0.54-0.75; P < .00001; P for heterogeneity < .0001), which, however, was related to the differential use of glycoprotein IIb/IIIa inhibitors (r = -0.02 [-0.033 to -0.0032]; P = .02) and did not translate into survival benefits.. In patients undergoing percutaneous coronary interventions, bivalirudin is not associated with a reduction in mortality compared with heparin but does increase stent thrombosis. The reduction in bleeding complications observed with bivalirudin does not translate into survival benefits but is rather influenced by a differential use of glycoprotein IIb/IIIa inhibitors.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Heparin; Hirudins; Humans; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins

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

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

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

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

The 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

A parenteral anticoagulant is indicated in patients with acute coronary syndromes. Which anticoagulant should be preferred in each setting is not clearly established. Bivalirudin administration was considered in acute coronary syndromes after several clinical trials showed decreased bleeding risk with its use compared with the association of unfractionated heparin (UFH) with glycoprotein IIb/IIIa inhibitors (GPIs). Most recent data demonstrate that the bleeding benefit identified in the previous studies was not due to bivalirudin's properties but to higher bleeding incidence in the comparator arm due to the disproportional use of GPIs with heparin. This paper reviews clinical evidence on bivalirudin as anticoagulant in stable angina and acute coronary syndromes.

Topics: Acute Coronary Syndrome; Angina, Stable; Animals; Fibrinolytic Agents; Hirudins; Humans; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins

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

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

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

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

Antiplatelet and anticoagulant drugs are the mainstay of treatment of acute coronary syndrome (ACS). The last 30 years have seen the development of various agents, a deeper understanding of the pathobiology of this disease, and an evolution in its treatment. We review the role of contemporary agents in ACS and highlight key clinical trials of these agents.

Topics: Acute Coronary Syndrome; Adenosine; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Clopidogrel; Dabigatran; Enoxaparin; Fondaparinux; Heparin; Hirudins; Humans; Morpholines; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Ticagrelor; Ticlopidine; Warfarin

Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Anticoagulants; Aspirin; Drug Therapy, Combination; Enoxaparin; Eptifibatide; Fondaparinux; Heparin; Hirudins; Humans; Lactones; Peptide Fragments; Peptides; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Pyridines; Receptors, Thrombin; Recombinant Proteins; Thiophenes; Ticagrelor; Tirofiban; Tyrosine; Warfarin

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

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

Major bleeding remains a major risk factor for percutaneous coronary intervention of acute coronary syndromes and is associated with higher morbidity, mortality, prolonged hospital stay and costs. With the recognition that bleeding is an important factor in patient outcomes, the prevention of bleeding has become as important a goal as the prevention of ischaemia. The direct thrombin inhibitor bivalirudin has been shown to reduce ischaemia and importantly, is associated with less bleeding. In this article we review the evidence base that supports the use of bivalirudin across all spectrums of coronary syndromes and percutaneous coronary intervention. An algorithm for the use of bivalirudin in high risk subgroups and coronary syndromes is suggested.

Topics: Acute Coronary Syndrome; Algorithms; Antithrombins; Hirudins; Humans; Length of Stay; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Recombinant Proteins

The efficacy and safety of heparin and low-molecular-weight heparins (LMWHs) are well documented in venous and arterial thromboembolism. Several drawbacks of heparins have inspired the development of newer parenteral anticoagulants for specific indications, including heparin-induced thrombocytopenia (HIT) and percutaneous coronary interventions (PCI). The direct thrombin inhibitors recombinant hirudin and argatroban are now established alternatives for HIT patients, and bivalirudin is one of the most used anticoagulants in PCI. The pentasaccharide fondaparinux is an alternative for LMWH for thromboprophylaxis in various clinical settings and for patients with an acute coronary syndrome (ACS) not scheduled for PCI. In Europe, it was recently approved for treatment of superficial vein thrombosis. Further development of new parenteral anticoagulants is slow and the emphasis has shifted towards development of new oral anticoagulants and antiplatelet drugs. Still, promising new anticoagulants, some targeting less conventional targets in the coagulation system, have been developed and will undergo further clinical evaluation.

Topics: Acute Coronary Syndrome; Antithrombins; Arginine; Fondaparinux; Hirudin Therapy; Hirudins; Humans; Infusions, Parenteral; Peptide Fragments; Percutaneous Coronary Intervention; Pipecolic Acids; Polysaccharides; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Venous Thromboembolism

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

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

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

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

Percutaneous coronary intervention (PCI) is currently the standard of care for patients presenting with acute coronary syndrome (ACS), as well those patients with "stable" angina who have failed medical therapy in whom PCI is an acceptable alternative to surgical revascularization. The aim of adjunctive antiplatelet and antithrombotic therapy during PCI is to alleviate the risks associated with platelet activation and aggregation, iatrogenic plaque rupture, and thrombus formation during. The aim of this review is to summarize the evidence that has emerged from the randomized studies comparing a strategy combining heparin and a glycoprotein IIb/IIIa inhibitor (GPI) with that of bivalirudin in patients undergoing elective and urgent PCI.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Drug Therapy, Combination; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins

Limitations and contraindications of heparins and oral vitamin K antagonists have led to the development of new anticoagulant drugs over the last few years. Argatroban is an intravenous direct thrombin inhibitor currently indicated for the prophylaxis and treatment of thrombosis associated with heparin-induced thrombocytopenia (HIT) and for patients at risk of HIT undergoing percutaneous coronary intervention (PCI). The role of argatroban for the treatment of acute coronary syndrome (ACS) is under evaluation.. This article reviews the potential use of argatroban for the treatment of ACS and presents the pharmacokinetic data currently available. The authors also present the pharmacodynamic literature of agratroban in addition to highlighting the safety and tolerability of the drug.. Theoretically, argatroban's pharmacokinetics makes it an attractive alternative to heparin. Pharmacological advantages of argatroban over heparin include a more-predictable anticoagulant response and the absence of a risk of HIT. Furthermore, argatroban has a fast and predictable dose-dependent anticoagulant effect with low inter-individual variability. It is non-immugenic, not susceptible to degradation by proteases and it is cleared via the liver. These characteristics confer argotroban a different profile from other anticoagulants. Agatroban is an effective alternative for patients when heparin, lepirudin and bivalirudin cannot be used. Its utility in ACS and PCI in non-HIT patients has been evaluated but further studies are warranted to define its role in this context.

Topics: Acute Coronary Syndrome; Animals; Antithrombins; Arginine; Disease Models, Animal; Drug Evaluation; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Pipecolic Acids; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombosis

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

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

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Cyclic N-Oxides; Fondaparinux; Hirudins; Humans; Morpholines; Peptide Fragments; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes

Bivalirudin (Angiox®; Angiomax®), a direct thrombin inhibitor, is an intravenous anticoagulant. The efficacy of bivalirudin in the management of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) or ST-segment elevation myocardial infarction (STEMI) planned for invasive interventions has been shown in large, pivotal, open-label trials. Bivalirudin provided similar ischaemic protection to heparin plus a glycoprotein (GP) IIb/IIIa inhibitor, but with a significant reduction in bleeding events, in patients with NSTE-ACS planned for urgent or early intervention and those with STEMI planned for primary percutaneous coronary intervention (PCI). Mortality rates were also significantly lower in patients with STEMI receiving bivalirudin than in those receiving heparin plus a GP IIb/IIIa inhibitor in the key trial of patients with STEMI. Based on this clinical data, modelled cost-utility analyses from the perspective of various UK NHS providers have predicted that bivalirudin would be highly likely to be cost effective with regard to the cost per QALY gained relative to a heparin plus GP IIb/IIIa inhibitor-based strategy over a lifetime horizon in these patient populations. In patients with NSTE-ACS planned for urgent or early invasive intervention, a bivalirudin-based strategy was considered to be cost effective in the UK, Scotland and Wales. In patients with STEMI planned for primary PCI, a bivalirudin-based strategy was dominant in the UK and Scotland. Parallel and sensitivity analyses demonstrated that base-case conclusions were robust over a range of plausible changes in parameter estimates and assumptions, including changes made to more closely reflect current local clinical practice. In addition, budgetary impact analyses in several countries suggested that the implementation of a bivalirudin-based strategy, instead of a heparin plus GP IIb/IIIa inhibitor-based strategy, would be cost saving from a hospital perspective in patients with NSTE-ACS undergoing urgent or early PCI, as well as in patients with STEMI undergoing primary PCI. Likewise, prospective and retrospective treatment cost studies in the US indicated that treatment with bivalirudin was less costly than treatment with heparin plus a GP IIb/IIIa inhibitor in these indications. In conclusion, available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of strategies based on bivalirudin over those based on heparin plus a GP IIb/

Topics: Acute Coronary Syndrome; Antithrombins; Clinical Trials as Topic; Cost Savings; Cost-Benefit Analysis; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Antithrombotic therapy plays an integral role in percutaneous coronary intervention (PCI). Bivalirudin has been evaluated in elective procedures and across the spectrum of acute coronary syndromes and is associated with decreased bleeding events compared to unfractionated heparin (UFH) in combination with glycoprotein IIb/IIIa inhibitors (GPI) when used for the duration of PCI. The use of bivalirudin beyond the end of PCI is not as well established but is being explored as an option for specific patients.. A small increase in stent thrombosis and ischemic events has been identified in large clinical trials using bivalirudin for acute coronary syndromes (ACS). The reasons for this finding are unclear, but may be related to the short duration of bivalirudin or the timing and dose of antiplatelet therapies in the trials. Two small, single center trials have evaluated bivalirudin continued for 4 h beyond the end of PCI. These trials suggest that prolonged bivalirudin infusions result in less periprocedural myocardial infarction with no increase in bleeding compared to intraprocedural only bivalirudin. However, these studies were not powered to identify a difference in bleeding. Efforts to decrease periprocedural myocardial infarction should include the appropriate use of oral antiplatelet agents. An adequate and appropriately timed loading dose of thienopyridines plays a key role in decreasing complications of PCI.. The strategy of prolonging the bivalirudin infusion at a reduced infusion rate for 4 h after completion of the PCI procedure was explored and offers promising results.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Dose-Response Relationship, Drug; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Stents; Thrombosis; Time Factors

Although percutaneous coronary intervention (PCI) is a highly effective modality for the management of acute coronary syndromes, it can potentiate the existing prothrombotic state around lesion areas and lead to ischaemic complications. Adjunctive pharmacologic treatment with heparin reduces the risk of ischaemic events, but the utility of heparin is limited by its unpredictable pharmacodynamic effects and its inability to modulate fibrin-bound thrombin. Additionally, a potential risk of heparin-induced thrombocytopenia is associated with heparin use. Direct thrombin inhibitors (DTIs) have emerged as potential alternatives to heparin in patients undergoing PCI. Bivalirudin is a DTI indicated for use in PCI. Results from various studies have suggested clinical benefit associated with the use of bivalirudin, driven primarily by the reduction in bleeding risks compared with the standard treatment regimens. Of concern, however, is a significant increase in acute stent thrombosis with bivalirudin monotherapy compared with heparin plus GPIIb/IIIa inhibitors following primary PCI for ST-segment elevation myocardial infarction (STEMI). Desirudin is a highly potent DTI with greater binding affinity than bivalirudin for thrombin. This report provides a comparative overview of the pharmacology and clinical utility of desirudin and bivalirudin in the setting of PCI.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Clinical Trials as Topic; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Stents

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

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

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

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

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

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

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

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

Among the current agents in the class of direct thrombin inhibitors, bivalirudin (Angiomax(®), The Medicines Company, NJ, USA) has seen increased use in cardiovascular medicine over the past decade through its primary indication as an anticoagulant used during percutaneous coronary interventions. Bivalirudin has been further investigated and used as the anticoagulation strategy in the setting of cardiac and endovascular surgical procedures and is frequently utilized in the management of patients with heparin-induced thrombocytopenia. In comparison with heparin, bivalirudin exhibits a low immunogenic profile and provides similar or reduced major bleeding rates as well as a predictable degree of anticoagulation that is dose related. Bivalirudin primarily undergoes dual elimination via proteolytic cleavage and renal elimination, and requires dose adjustment in the setting of severe renal dysfunction. Given the body of supportive data, bivalirudin is likely to continue to figure prominently as a reliable and efficient anticoagulation strategy. Additional agents in the class of direct thrombin inhibitors are under investigation and may find increasing clinical use.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Endovascular Procedures; Hemostasis, Surgical; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombocytopenia

Bivalirudin, a direct thrombin inhibitor, has unique attributes including predictable pharmacokinetics, a reduction in bleeding complications and avoidance of heparin induced thrombocytopenia.. We critically review the role of bivalirudin in the management of patients with acute coronary syndrome in light of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.. Data from the ACUITY trial was critically reviewed along with other contemporary data.. In the ACUITY trial, bivalirudin monotherapy was associated with rates of ischemic events that were noninferior to those associated with heparin plus glycoprotein IIb/IIIa inhibition, but was associated with a significantly reduced incidence of major bleeding. Bivalirudin seems to be an attractive antithrombotic agent in patients with acute coronary syndrome undergoing early invasive management.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Fibrinolytic Agents; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombin

Acute coronary syndromes still account for high mortality in many countries. Antithrombotic therapy represents a cornerstone in the therapy of acute coronary syndromes. Recent research has focussed on improving anti-ischemic potency and reducing bleeding complications as well as improving predictability of antithrombotic efficacy.. New antithrombotic drugs such as the factor Xa antagonists and the direct thrombin inhibitors have been developed and evaluated in clinical trials. Fondaparinux and bivalirudin are approved for clinical use in acute coronary syndromes. They improve the risk/benefit ratio and make routine control of their antithrombotic effect unnecessary. Other agents are being developed to further improve and facilitate antithrombotic therapy in acute coronary syndromes.. Antithrombotic therapy is essential in acute coronary syndrome. New drugs are being developed to enter clinical practice and improve efficacy and safety of this therapeutic strategy.

Topics: Acute Coronary Syndrome; Anticoagulants; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Peptide Fragments; Polysaccharides; Recombinant Proteins; Thrombin

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

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

The crucial aim in the emergency management of patients presenting with chest pain is the identification of acute coronary syndromes (ACS) and the initiation of appropriate treatment. Institution-specific triage to initial medical or interventional therapies is influenced by the availability of percutaneous coronary intervention (PCI) facilities. Although the use of invasive strategies has increased, most US hospitals do not have PCI facilities. Pharmacological management is an integral part of all treatment strategies, regardless of the availability of interventional capability. Given the growing importance of invasive management strategies, a therapy that is compatible with both medical and invasive therapy options is becoming increasingly important. Aspirin and clopidogrel are recommended for patients with ACS regardless of the conservative or invasive management strategy. With enoxaparin, patients with ACS can seamlessly transition from the medical management phase to the interventional management phase without the need for introducing a second anticoagulant in the cardiac catheterization laboratory. Fondaparinux can be used for patients with ACS treated medically, but should not be used alone during PCI because of the risk of catheter thrombosis. Bivalirudin can be used in non-ST-segment elevation myocardial infarction patients who are managed invasively.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Emergency Service, Hospital; Enoxaparin; Fondaparinux; Health Services Accessibility; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Polysaccharides; Recombinant Proteins; Ticlopidine; Triage; United States

Diabetic patients with acute coronary syndromes (ACSs) are at a high risk for subsequent cardiovascular events but derive, at the same time, greater benefit from evidence-based therapy than non-diabetic individuals. State-of-the-art anti-thrombotic therapy includes a triple anti-platelet combination - aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa receptor inhibitors - and unfractionated heparin or enoxaparin. For low- or medium-risk individuals, a treatment based on aspirin, clopidogrel and bivalirudin is a valuable alternative. Prasugrel, a new and more potent inhibitor of the platelet P2Y(12) receptor, has to be regarded as the most promising anti-thrombotic agent for diabetic patients with ACS. This agent may replace clopidogrel - and possibly GP IIb/IIIa inhibitors - in the future. In addition to aggressive anti-thrombotic therapy, diabetic patients should undergo systematic early invasive angiography if presenting with non-ST-segment elevation ACS, and immediate percutaneous coronary intervention if presenting with ST-segment elevation myocardial infarction. Indeed, the benefit derived from these strategies appears to be more pronounced in the diabetic population than in non-diabetic individuals. Despite the benefit, multiple surveys have demonstrated that, in the setting of ACS, diabetic patients receive evidence-based therapy less frequently than non-diabetic counterparts.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Blood Glucose; Clopidogrel; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Enoxaparin; Hirudins; Humans; Hypoglycemic Agents; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Recombinant Proteins; Thiophenes; Thrombosis; Ticlopidine

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Emergency Service, Hospital; Evidence-Based Medicine; Fondaparinux; Hirudins; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Platelet activation and aggregation are important pathophysiologic elements of both non-ST-elevation acute coronary syndromes and the ischemic complications of percutaneous coronary intervention, making antiplatelet agents necessary components of the pharmacotherapeutic treatment paradigm for these patients. This review evaluates and interprets the role of oral antiplatelet agents, glycoprotein IIb-IIIa inhibitors, and bivalirudin in the context of current clinical evidence and practice.. The current standard of care for patients with non-ST-elevation acute coronary syndromes--aspirin, clopidogrel, and glycoprotein IIb-IIIa inhibitors for the majority of patients--is being challenged by recent clinical trials (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment, Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2, Randomized Evaluation of Percutaneous coronary intervention Linking Angiomax to Reduced Clinical Events-2, Acute Catheterization and Urgent Intervention Triage StrategY), raising important questions regarding the value of glycoprotein IIb-IIIa inhibitors as accompaniments of high-dose clopidogrel pretreatment and increased use of the anticoagulant bivalirudin.. Current data indicate that antiplatelet regimens consisting of aspirin, clopidogrel, and a glycoprotein IIb-IIIa inhibitor provide substantial benefit among patients who undergo percutaneous coronary intervention. Optimized antiplatelet and anticoagulant therapy--including aspirin, clopidogrel, a glycoprotein IIb-IIIa inhibitor, and an anticoagulant--may reduce the incidence of subclinical and clinical events.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Ticlopidine

With the availability of new data and the recent release of new European and US guidelines, contemporary care paradigms for the treatment of patients with non-ST-elevation acute coronary syndromes (NSTE ACS), including those undergoing percutaneous coronary intervention, are likely to undergo substantial changes. In recognition of this shifting landscape as well as the impact of new guidelines on care models for the treatment of patients with NSTE ACS, a roundtable was convened on October 25, 2007, to discuss the implications of these changes. The purpose of this review is to summarize the presentations and subsequent discussions from the roundtable, which examined the guidelines and evidence from a variety of perspectives, and to explore the best ways to incorporate new treatment paradigms into everyday clinical care. The multiple viewpoints expressed by the roundtable attendees illustrate the recognition that at this point, consensus has not been reached on the optimum algorithm for treatment of these patients. This article focuses on issues discussed during the roundtable from the perspective of the practicing cardiologist.

Topics: Acute Coronary Syndrome; Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Cardiovascular Agents; Clinical Trials as Topic; Clopidogrel; Emergency Treatment; Evidence-Based Medicine; Fibrinolytic Agents; Hirudins; Humans; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Hemorrhage; Practice Guidelines as Topic; Prasugrel Hydrochloride; Recombinant Proteins; Risk Assessment; Stents; Thiophenes; Thrombosis; Ticlopidine

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

Bivalirudin is a 20-amino acid synthetic polypeptide that directly inhibits both fibrin-bound and soluble thrombin. In a randomized, open-label, phase III study (ACUITY) in 13,819 patients with acute coronary syndromes (unstable angina or non-ST-segment elevation myocardial infarction) in whom urgent or early intervention was planned, both bivalirudin plus a glycoprotein (GP) IIb/IIIa inhibitor and bivalirudin alone were noninferior to heparin plus a GP IIb/IIIa inhibitor for the primary endpoint of composite ischaemia (myocardial infarction, unplanned revascularization or death from any cause) at 30 days. The primary endpoint of major bleeding not related to coronary artery bypass graft surgery had occurred in significantly fewer recipients of bivalirudin alone than of heparin plus a GP IIb/IIIa inhibitor after 30 days. Bivalirudin plus a GP IIb/IIIa inhibitor was noninferior to the heparin regimen with regard to this bleeding event. Bivalirudin alone was also associated with a significantly lower incidence of the primary net clinical outcome endpoint (composite ischaemia or major bleeding) after 30 days. Bivalirudin plus a GP IIb/IIIa inhibitor was noninferior to the heparin regimen with regard to this endpoint. The findings of ACUITY at 1 year indicate that both bivalirudin plus a GP IIb/IIIa inhibitor and bivalirudin alone were as effective as heparin plus a GP IIb/IIIa inhibitor with regard to the long-term incidence of composite ischaemia and all-cause mortality.

Topics: Acute Coronary Syndrome; Animals; Antithrombins; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

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

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

The acute coronary syndrome (ACS) is one of the most frequent diagnoses in cardiology. The therapeutic corner-stones of ACS are PCI (percutaneous coronary intervention) and inhibition of blood coagulation. Current antiplatelet therapy consists of aspirin in combination with clopidogrel and glycoprotein IIb/IIIa blockade if needed. Prasugel is a new antiplatelet agent that is in the process of being approved for routine clinical use. In terms of antithrombotic therapy latest developments focus on drugs with anti-factor Xa activity, such as fondaparinux, or direct anti-thrombin activity, such as bivalirudin. This review discusses latest developments in the field of anti-platelet and anti-thrombotic therapy for ACS.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Hirudins; Humans; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Recombinant Proteins

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

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

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

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

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

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

The acute coronary syndromes (i.e., ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina) share a common pathophysiology: the rupture or breakdown of atheromatous plaque superimposed on intracoronary thrombosis (i.e., atherothrombosis). The aim of this review article was to summarize developments occurring during the last year in antithrombotic therapy for non-ST-segment elevation acute coronary syndromes. Four specific issues are considered: pretreatment with clopidogrel before percutaneous coronary intervention, antiplatelet resistance, indications for glycoprotein IIb/IIIa inhibitors in patients pretreated with clopidogrel, and the role of bivalirudine and fondaparinux in the treatment of these patients.

Topics: Acute Coronary Syndrome; Anticoagulants; Clopidogrel; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Peptide Fragments; Polysaccharides; Recombinant Proteins; Ticlopidine

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

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

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

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

Acute kidney injury (AKI) is a critical complication among patients with acute coronary syndrome (ACS) undergoing invasive management. The value of adjunctive antithrombotic strategies, such as bivalirudin or unfractionated heparin (UFH) on the risk of AKI is unclear.. Among 7213 patients enrolled in the MATRIX-Antithrombin and Treatment Duration study, 128 subjects were excluded due to incomplete information on serum creatinine (sCr) or end-stage renal disease on dialysis treatment. The primary endpoint was AKI defined as an absolute (>0.5 mg/dL) or a relative (>25%) increase in sCr. AKI occurred in 601 patients (16.9%) treated with bivalirudin and 616 patients (17.4%) treated with UFH [odds ratio (OR): 0.97; 95% confidence interval (CI): 0.85-1.09; P = 0.58]. A >25% sCr increase was observed in 597 patients (16.8%) with bivalirudin and 616 patients (17.4%) with UFH (OR: 0.96; 95% CI: 0.85-1.08; P = 0.50), whereas a >0.5 mg/dL absolute sCr increase occurred in 176 patients (5.0%) with bivalirudin vs. 189 patients (5.4%) with UFH (OR: 0.92; 95% CI: 0.75-1.14; P = 0.46). By implementing the Kidney Disease Improving Global Outcomes (KDIGO) criteria, the risk of AKI was not significantly different between bivalirudin and UFH groups (OR: 0.88; 95% CI: 0.72-1.07; P = 0.21). Subgroup analyses of the primary endpoint suggested a benefit with bivalirudin in patients randomized to femoral access.. Among ACS patients undergoing invasive management, the risk of AKI was not significantly lower with bivalirudin compared with UFH.. clinicaltrials.gov NCT01433627.

Topics: Acute Coronary Syndrome; Acute Kidney Injury; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Our aim was to assess whether bivalirudin compared with unfractionated heparin (UFH) is associated with consistent outcomes in males and females with acute coronary syndrome (ACS) undergoing invasive management.. In the MATRIX programme, 7,213 patients were randomised to bivalirudin or UFH. Patients in the bivalirudin group were subsequently randomly assigned to receive or not a post-PCI bivalirudin infusion. The 30-day co-primary outcomes were major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACE or major bleeding. The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target vessel revascularisation (TVR), definite stent thrombosis (ST), or NACE. The rate of MACE was not significantly lower with bivalirudin than with heparin in male (rate ratio [RR] 0.90, 95% confidence interval [CI]: 0.75-1.07; p=0.22) and female patients (RR 1.06, 95% CI: 0.80-1.40; p=0.67) without significant interaction (pint=0.31), nor was the rate of NACE (males: RR 0.85, 95% CI: 0.72-1.01; p=0.07; females: RR 0.98, 95% CI: 0.76-1.28; p=0.91; pint=0.38). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent TVR, definite ST, or NACE (males: RR 0.84, 95% CI: 0.66-1.07; p=0.15; females: RR 1.06, 95% CI: 0.74-1.53; p=0.74; pint=0.28).. In ACS patients, the rates of MACE and NACE were not significantly lower with bivalirudin than with UFH in both sexes. The rate of the composite of urgent TVR, definite ST, or NACE was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion in both sexes.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Female; Heparin; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

The value of prolonged bivalirudin infusion after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients with or without ST-segment elevation remains unclear.. The purpose of this study was to assess efficacy and safety of a full or low post-PCI bivalirudin regimen in ACS patients with or without ST-segment elevation.. The MATRIX program assigned bivalirudin to patients without or with a post-PCI infusion at either a full (1.75 mg/kg/h for ≤4 h) or reduced (0.25 mg/kg/h for ≤6 h) regimen at the operator's discretion. The primary endpoint was the 30-day composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (composite of all-cause death, myocardial infarction, or stroke, or major bleeding).. Among 3,610 patients assigned to bivalirudin, 1,799 were randomized to receive and 1,811 not to receive a post-PCI bivalirudin infusion. Post-PCI full bivalirudin was administered in 612 (ST-segment elevation myocardial infarction [STEMI], n = 399; non-ST-segment elevation acute coronary syndromes [NSTE-ACS], n = 213), whereas the low-dose regimen was administered in 1,068 (STEMI, n = 519; NSTE-ACS, n = 549) patients. The primary outcome did not differ in STEMI or NSTE-ACS patients who received or did not receive post-PCI bivalirudin. However, full compared with low bivalirudin regimen remained associated with a significant reduction of the primary endpoint after multivariable (rate ratio: 0.21; 95% CI: 0.12 to 0.35; p < 0.001) or propensity score (rate ratio: 0.16; 95% CI: 0.09 to 0.26; p < 0.001) adjustment. Full post-PCI bivalirudin was associated with improved outcomes consistently across ACS types compared with the no post-PCI infusion or heparin groups.. In ACS patients with or without ST-segment elevation, the primary endpoint did not differ with or without post-PCI bivalirudin infusion but a post-PCI full dose was associated with improved outcomes when compared with no or low-dose post-PCI infusion or heparin (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627).

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Dose-Response Relationship, Drug; Female; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Care; Recombinant Proteins; ST Elevation Myocardial Infarction; Treatment Outcome

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

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

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

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

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

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

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

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

Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromes patients (ACS) undergoing percutaneous coronary intervention (PCI) with bivalirudin compared to heparin. We aimed to investigate the potential mechanisms responsible for thrombus formation under bivalirudin.. We compared heparin and bivalirudin during PCI for ACS in a prospective monocentre randomized study. Twenty patients were included after coronary angiography and received a loading dose (LD) of 180mg of ticagrelor at the time of PCI. They were randomly assigned to heparin (70UI/kg) intra-venous (IV) bolus or bivalirudin IV bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg/h until the end of the PCI. The VASP index and thrombin generation test were used to assess the course of platelet reactivity (PR) and thrombin generation.. Thrombin generation and PR were identical in both groups at baseline. There was no difference in the course of PR following the LD over time. An optimal PR inhibition was reached 4h after the LD of ticagrelor. Heparin and bivalirudin infusion effectively inhibited thrombin generation during PCI. However, 4h after the end of bivalirudin infusion, thrombin generation had returned to its baseline value whereas in the heparin group it remained significantly inhibited compared to baseline and to the bivalirudin group 4h after the end of the infusion (p<0.01 and p<0.02 respectively).. The present study suggests that the short half-life of bivalirudin and the quick restoration of thrombin activity at a time when optimal PR is not reached may be responsible for acute stent thrombosis. Clinicaltrial.gov: NCT02428725.

Topics: Acute Coronary Syndrome; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antithrombins; Drug-Eluting Stents; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Recombinant Proteins; Thrombosis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The randomized TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 trial compared prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Patients treated with prasugrel had fewer ischemic events but more procedure-related bleeding. In the present study, we aimed to determine the effect of bivalirudin on bleeding in patients treated with prasugrel. A total of 692 patients with consecutive acute coronary syndrome underwent PCI with stent implantation and were anticoagulated with bivalirudin. The patients were divided into 2 groups according to the antiplatelet regimen (clopidogrel or prasugrel) chosen during or just after PCI. The bleeding complications during hospitalization were tabulated. Ischemic events were analyzed during hospitalization and at 30 days. Prasugrel was used in 96 patients (13.9%) and clopidogrel in 596 (86.1%). The clinical and procedural characteristics were similar, although the clopidogrel patients more often reported systemic hypertension (p = 0.01), previous PCI (p <0.001), and chronic renal insufficiency (p = 0.05). During hospitalization, the bleeding and ischemic complication rates were similar and low in both groups (major in-hospital complications 4.2% for clopidogrel vs 2.1% for prasugrel, p = 0.6; Thrombolysis In Myocardial Infarction major bleeding 2.5% vs 2.1%, p = 1.00; Thrombolysis In Myocardial Infarction minor bleeding 4.2% vs 5.2%, p = 0.6). At 30 days, no differences were found in ischemic events between both groups (target vessel revascularization/major adverse cardiac events 5.4% vs 2.1%, p = 0.2). In conclusion, prasugrel, when given after bivalirudin as the intraprocedural antithrombin agent for patients with acute coronary syndrome undergoing PCI, is as safe and effective as clopidogrel.

Topics: Acute Coronary Syndrome; Antithrombins; Coronary Angiography; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Piperazines; Prasugrel Hydrochloride; Preoperative Care; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Retrospective Studies; Thiophenes; Treatment Outcome

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

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

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

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

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

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

We sought to investigate the predictive value of the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (SS) for risk assessment of 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI).. In the SYNTAX trial, the SS was effective in risk-stratifying patients with left main and triple-vessel coronary disease, the majority of whom had stable ischemic heart disease.. The SS was determined in 2,627 patients with non-ST-segment elevation acute coronary syndromes undergoing PCI in the angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial. Patients were stratified according to tertiles of the SS: <7 (n = 854), ≥ 7 and <13 (n = 825), and ≥ 13 (n = 948).. Among patients in the first, second, and third SS tertiles, the 1-year rates of mortality were 1.5%, 1.6%, and 4.0%, respectively (p = 0.0005); the cardiac mortality rates were 0.2%, 0.9%, and 2.7%, respectively (p < 0.0001); the myocardial infarction (MI) rates were 6.3%, 8.3%, and 12.9%, respectively (p < 0.0001); and the target vessel revascularization (TVR) rates were 7.4%, 7.0%, and 9.8%, respectively (p = 0.02). By multivariable analysis, the SS was an independent predictor of 1-year death (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01 to 1.07; p = 0.005), cardiac death (HR: 1.06, 95% CI: 1.03 to 1.09; p = 0.0002), MI (HR: 1.03, 95% CI: 1.02 to 1.05; p < 0.0001), and TVR (HR: 1.03, 95% CI: 1.02 to 1.05; p < 0.0001). The SS affected death, cardiac death, and MI both within the first 30 days after PCI and between 30 days and 1 year, whereas it affected TVR primarily within the first 30 days. The predictive value of an increased SS was consistent among multiple pre-specified subgroups.. In patients with non-ST-segment elevation acute coronary syndromes undergoing PCI, the SS is an independent predictor of the 1-year rates of death, cardiac death, MI, and TVR. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Cardiac Catheterization; Coronary Angiography; Coronary Artery Bypass; Electrocardiography; Emergency Treatment; Female; Heparin, Low-Molecular-Weight; Hirudins; Hospital Mortality; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; ROC Curve; Severity of Illness Index; Statistics, Nonparametric; Survival Analysis; Treatment Outcome; Triage

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

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

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

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

The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial demonstrated that bivalirudin monotherapy significantly reduces major bleeding compared with heparin (unfractionated or enoxaparin) or bivalirudin plus a glycoprotein IIb/IIIa inhibitor in acute coronary syndromes. Whether vascular closure devices (VCD) impact these results is unknown. Therefore, this study sought to determine whether VCD impact major access site bleeding (ASB) in patients with acute coronary syndromes undergoing early invasive management by the femoral approach.. Major ASB in ACUITY was defined as ASB requiring interventional or surgical correction, hematoma > or =5 cm at the access site, retroperitoneal bleeding, or hemoglobin drop > or =3 g/dL with ecchymosis or hematoma <5 cm, oozing blood, or prolonged bleeding (>30 minutes) at the access site. Stepwise logistical regression was performed to identify the independent determinants of ASB. Of 11 621 patients undergoing angiography with or without percutaneous coronary intervention by the femoral approach, 4307 (37.1%) received a VCD and 7314 (62.9%) did not. Rates of major ASB were lower with VCD compared with no VCD (2.5% versus 3.3%, relative risk, 0.76; 95% CI, 0.61 to 0.94; P=0.01) and were lowest in patients treated with bivalirudin monotherapy and a VCD (0.7%). Stepwise logistic regression revealed that a VCD (odds ratio, 0.78; 95% CI, 0.61 to 0.99; P=0.04) and bivalirudin monotherapy (odds ratio, 0.35; 95% CI, 0.25 to 0.49; P<0.0001) were both independent determinates of freedom from major ASB.. In patients with acute coronary syndromes undergoing an early invasive management strategy by the femoral approach, the use of a VCD, bivalirudin monotherapy, or both minimizes rates of major ASB. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00093158.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angiography; Angioplasty, Balloon, Coronary; Equipment and Supplies; Female; Femoral Artery; Fibrinolytic Agents; Hematoma; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Peptide Fragments; Recombinant Proteins

Outcomes of patients presenting with acute coronary syndromes are improved with an early invasive approach; however, approximately one third of these patients are treated medically after angiographic screening. We sought to assess the predictors of adverse cardiac events in patients with acute coronary syndrome assigned to medical management.. This substudy of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial included 4491 acute coronary syndrome patients treated medically after angiographic triage. Rates of bleeding and composite ischemia (death, myocardial infarction, revascularization) were compared among the 3 antithrombotic treatment arms. Composite ischemia occurred in 399 patients (9.5%) at 1 year. Treatment with bivalirudin glycoprotein IIb/IIIa inhibitors significantly reduced major bleeding at 30 days (2.5% bivalirudin monotherapy; P=0.005, 2.0% bivalirudin plus glycoprotein IIb/IIIa inhibitors; P=0.0002 versus 4.4% heparin with glycoprotein IIb/IIIa inhibitors). Composite ischemic events at 1 year were not significantly different in the 3 groups (bivalirudin monotherapy, 9.6%; bivalirudin plus glycoprotein IIb/IIIa inhibitors, 9.7%; heparin plus glycoprotein IIb/IIIa inhibitors, 9.1%). Independent predictors of composite ischemia were mostly angiographic factors at 30 days, including jeopardy score and coronary ectasia, and at 1 year, including previous percutaneous coronary intervention, jeopardy score, coronary ectasia, and increasing number of diseased vessels.. Among the ACUITY acute coronary syndrome patients treated medically after angiographic triage, bivalirudin therapy significantly reduced bleeding complications compared with heparin without any negative impact on ischemic outcomes at 1 year. The most powerful predictors of ischemic outcomes were angiographic rather than traditional clinical parameters, supporting the early use of angiographic screening in the moderate- and high-risk but medically treated acute coronary syndrome population. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Coronary Angiography; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Predictive Value of Tests; Recombinant Proteins; Risk Factors; Treatment Outcome

Clinical outcomes in patients with acute coronary syndromes randomized in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial who underwent percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) were examined. The ACUITY trial assessed the safety and efficacy of bivalirudin alone versus bivalirudin plus a glycoprotein (GP) IIb/IIIa inhibitor versus heparin plus a GP IIb/IIIa inhibitor in 13,819 patients with moderate- and high-risk acute coronary syndromes, 7,789 of whom underwent PCI. A total of 329 patients (4.2%) underwent PCI of SVGs in ACUITY. The primary end points at 30 days were composite ischemia or major adverse cardiac events (death, myocardial infarction, or unplanned target vessel revascularization), major bleeding (unrelated to coronary artery bypass grafting), and net adverse clinical events (composite ischemia or major bleeding). The rates of ischemic, bleeding, and net clinical end points were similar with bivalirudin monotherapy, bivalirudin plus a GP IIb/IIIa inhibitor, and heparin plus a GP IIb/IIIa inhibitor. Net adverse clinical outcome rates at 30 days were 22%, 26%, and 22% (p = 0.67), respectively, for the 3 groups. Major adverse cardiac event rates at 1 year were 37%, 37%, and 43% (p = 0.95), respectively. Minor bleeding unrelated to coronary artery bypass grafting at 30 days was significantly lower with bivalirudin alone compared with heparin plus a GP IIb/IIIa inhibitor (26% vs 38%, p = 0.05). In conclusion, bivalirudin is an effective anticoagulant in PCI of SVGs in acute coronary syndromes, with similar rates of major adverse cardiac events and net adverse cardiac events and lower minor bleeding complications in comparison with heparin plus a GP IIb/IIIa inhibitor or bivalirudin plus a GP IIb/IIIa inhibitor.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Coronary Artery Bypass; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Saphenous Vein; Treatment Outcome

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

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

Women with non-ST-elevation acute coronary syndrome are at increased risk for ischemic and bleeding complications compared with men. We examined the impact of gender and antithrombotic therapy for non-ST-elevation acute coronary syndrome on outcomes in patients in the ACUITY trial. Patients were randomized to heparin (unfractionated or enoxaparin) plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin alone. We compared major bleeding unconnected to coronary artery bypass grafting, composite ischemia (death, myocardial infarction, or revascularization), and net clinical outcome (composite ischemia or bleeding) in (1) men versus women overall and undergoing percutaneous coronary intervention (PCI) and (2) women overall and undergoing PCI by antithrombotic strategy. Of 13,819 patients enrolled, 4,157 were women (30.1%). Women had similar 30-day composite ischemia (7% vs 8%, p = 0.07) but greater 30-day rates of major bleeding (8% vs 3% p <0.0001) and net clinical outcomes (13% vs 10% p <0.0001) than men. One-year composite ischemia and mortality was similar. In women, bivalirudin compared with heparin + GPI resulted in less 30-day major bleeding (5% vs 10%, p <0.0001) but similar composite ischemia (7% vs 6%, p = 0.15). No differences were observed in rates of 1-year composite ischemia or mortality in women who received bivalirudin versus heparin + GPI. Results were similar in women undergoing PCI. In conclusion, women had similar 30-day mortality and composite ischemia but higher net clinical adverse events due to more bleeding complications than men; 1-year mortality was similar for men and women. In women, bivalirudin monotherapy compared with a GPI-based strategy resulted in significantly decreased bleeding but similar rates of 1-year composite ischemia and mortality.

Topics: Acute Coronary Syndrome; Adult; Age Factors; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Cause of Death; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Enoxaparin; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Probability; Proportional Hazards Models; Recombinant Proteins; Reference Values; Risk Assessment; Severity of Illness Index; Sex Factors; Survival Analysis; Time Factors; Treatment Outcome

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

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

The objective was to assess the safety and efficacy of bivalirudin monotherapy in patients with high-risk acute coronary syndrome (ACS) presenting to the emergency department (ED).. Data from the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial were used to conduct a post hoc subgroup analysis of high-risk ACS patients (cardiac biomarker elevation or ST-segment deviation) who initially presented to the ED. The ACUITY trial randomized patients to receive heparin (unfractionated [UFH] or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Endpoints included composite ischemia, major bleeding (not coronary artery bypass graft (CABG) related), and net clinical outcome (major bleeding plus composite ischemia).. Of 13,819 participants in the ACUITY trial, 6,441 presented initially to the ED, met high-risk criteria, and were included in the primary analysis. Bivalirudin alone when compared to heparin plus GPI, after adjusting for covariates, was associated with an improvement in net clinical outcome (12.3% vs. 14.3%, adjusted odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.66 to 0.99), similar composite ischemia (9.3% vs. 9.1%, adjusted OR = 0.98, 95% CI = 0.77 to 1.24), and less major bleeding (4.0% vs. 6.8%, adjusted OR = 0.57, 95% CI = 0.42 to 0.75). Bivalirudin plus GPI when compared to heparin plus GPI had similar net clinical outcome (13.8% vs. 14.3%, adjusted OR = 0.91, 95% CI = 0.75 to 1.11), composite ischemia (8.8% vs. 9.1%, adjusted OR = 0.87, 95% CI = 0.69 to 1.11), and major bleeding (6.8% vs. 6.8%, adjusted OR = 1.01, 95% CI = 0.79 to 1.30).. Bivalirudin monotherapy decreases major bleeding while providing similar protection from ischemic events compared to heparin plus GPI in patients with high-risk ACS admitted through the ED.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Chi-Square Distribution; Comorbidity; Emergency Service, Hospital; Enoxaparin; Female; Heparin; Hirudins; Humans; Logistic Models; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Treatment Outcome; Triage

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

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

Our study sought to evaluate mechanisms of the current strategies for optimal anticoagulation during percutaneous coronary intervention (PCI).. Thirty-two high risk acute coronary syndrome patients were randomised to bivalirudin and provisional GPIIb/IIIa inhibition (GPIIb/IIIa) or unfractionated heparin (UFH) and mandatory GPIIb/IIIa. Flow cytometric measurements immediately after anticoagulation showed that, unlike UFH, bivalirudin did not activate platelets as indicated by P-selectin expression and fibrinogen binding while decreasing platelet-monocyte aggregates and monocyte expression of tissue factor. UFH released tissue factor pathway inhibitor (TFPI) during and immediately after PCI while bivalirudin (irrespective of GP IIb/IIIa) did not. Lower levels of TFPI with bivalirudin were seen during and immediately after PCI (P<0.01). Thrombin generation as indicated by prothrombin fragment F 1+2 levels was reduced during PCI in the UFH group (P<0.01) but not with bivalirudin. Soluble CD40 ligand is associated with thrombosis and levels were higher in the bivalirudin group irrespective of GPIIb/IIIa at the same stages (P<0.05).. Bivalirudin has some early advantages on platelet activation when compared to UFH. However, there are significant limitations in its mechanism of action, particularly a lack of release of tissue factor pathway inhibitor.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Biomarkers; Blood Coagulation; CD40 Ligand; Clopidogrel; Drug Therapy, Combination; Female; Fibrinogen; Heparin; Hirudins; Humans; Lipoproteins; Male; Membrane Glycoproteins; Middle Aged; Monocytes; Peptide Fragments; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prothrombin; Recombinant Proteins; Thromboplastin; Thrombosis; Ticlopidine; Treatment Outcome

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

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

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

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

Topics: Acute Coronary Syndrome; Anticoagulants; Enoxaparin; Hirudins; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Time Factors

This study was designed to determine the impact of bivalirudin on 1-year outcomes in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).. The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated that in moderate- and high-risk ACS patients undergoing PCI, bivalirudin alone compared to unfractionated heparin (UFH) or enoxaparin plus a glycoprotein (GP) IIb/IIIa inhibitor resulted in less major bleeding and similar ischemic outcomes at 30 days. The impact of bivalirudin on 1-year outcomes in ACS patients undergoing PCI is unknown.. In the ACUITY trial, 13,819 patients were enrolled, and 7,789 (56.4%) patients had PCI. Composite ischemia (death, myocardial infarction, or unplanned revascularization) and mortality at 1 year were assessed.. Among patients undergoing PCI, 2,561, 2,609, and 2,619 were randomized to UFH or enoxaparin plus a GP IIb/IIIa inhibitor, bivalirudin plus a GP IIb/IIIa inhibitor, and bivalirudin monotherapy, respectively. At 1 year, there were no differences in composite ischemia (17.8% vs. 19.4% vs. 19.2%, p = NS) or mortality (3.2% vs. 3.3% vs. 3.1%, p = NS) among the 3 groups, respectively.. Bivalirudin compared with UFH or enoxaparin plus a GP IIb/IIIa inhibitor results in similar rates of composite ischemia and mortality at 1 year in moderate- and high-risk ACS patients undergoing PCI.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Enoxaparin; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Time Factors

The aim of this study was to determine the economic impact of several anticoagulation strategies for moderate- and high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients managed invasively.. The ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial demonstrated that bivalirudin monotherapy yields similar rates of ischemic complications and less bleeding than regimens incorporating glycoprotein IIb/IIIa receptor inhibitors (GPI) for moderate- and high-risk NSTE-ACS.. In ACUITY, 7,851 U.S. patients were randomized to: 1) heparin (unfractionated or enoxaparin) + GPI; 2) bivalirudin + GPI; or 3) bivalirudin monotherapy. Patients assigned to GPI were also randomized to upstream GPI before catheterization or selective GPI only with percutaneous coronary intervention. Resource use data were collected prospectively through 30-day follow-up. Costs were estimated with standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule.. At 30 days, ischemic events were similar for all groups. Major bleeding was reduced with bivalirudin monotherapy compared with heparin + GPI or bivalirudin + GPI (p < 0.001). Length of stay was lowest with bivalirudin monotherapy or bivalirudin + catheterization laboratory GPI (p = 0.02). Despite higher drug costs, aggregate hospital stay costs were lowest with bivalirudin monotherapy (mean difference range: $184 to $1,081, p < 0.001 for overall comparison) and at 30 days (mean difference range: $123 to $938, p = 0.005). Regression modeling demonstrated that hospital savings were primarily due to less major and minor bleeding with bivalirudin ($8,658/event and $2,282/event, respectively).. Among U.S. patients in the ACUITY trial, bivalirudin monotherapy compared with heparin + GPI resulted in similar protection from ischemic events, reduced bleeding, and shorter length of stay. Despite higher drug costs, aggregate hospital and 30-day costs were lowest with bivalirudin monotherapy. Thus bivalirudin monotherapy seems to be an economically attractive alternative to heparin + GPI for patients with moderate- and high-risk NSTE-ACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Bypass; Drug Therapy, Combination; Female; Health Care Costs; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome; United States

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

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

We sought to evaluate clinical outcomes of patients with diabetes mellitus in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, overall and by treatment arm.. In the ACUITY trial, 13,819 patients with moderate- or high-risk acute coronary syndromes (ACS) were randomized to heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Compared with heparin plus GPI, bivalirudin monotherapy resulted in similar protection from ischemic events with less major bleeding. Whether these results apply to patients with diabetes is unknown.. We evaluated the impact of diabetes on 30-day net adverse clinical outcomes (composite ischemia [death, myocardial infarction, or unplanned ischemic revascularization] or major bleeding), overall and by antithrombotic strategy.. Diabetes was present in 3,852 randomized patients (27.9%). Compared with nondiabetic patients, diabetic patients had higher 30-day rates of net adverse clinical outcomes (12.9% vs. 10.6%; p < 0.001), composite ischemia (8.7% vs. 7.2%; p = 0.003), and major bleeding (5.7% vs. 4.2%; p < 0.001). Among diabetic patients, compared with heparin plus GPI, bivalirudin plus GPI resulted in similar rates of net adverse clinical outcomes (14.0% vs. 13.8%; p = 0.89), while bivalirudin monotherapy resulted in a similar rate of composite ischemia (7.9% vs. 8.9%; p = 0.39) and less major bleeding (3.7% vs. 7.1%; p < 0.001), yielding fewer net adverse clinical outcomes (10.9% vs. 13.8%; p = 0.02).. Diabetic patients with ACS managed invasively have higher rates of composite ischemia and major bleeding. Compared with treatment with heparin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding, resulting in a significant reduction in net adverse clinical outcomes.

Topics: Acute Coronary Syndrome; Acute Disease; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiac Catheterization; Diabetes Complications; Enoxaparin; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Treatment Outcome

The aim of this study was to compare outcomes in patients receiving consistent unfractionated heparin (UFH)/enoxaparin (ENOX) therapy and in those switched at randomization to bivalirudin monotherapy.. Crossover between UFH and ENOX has been associated with increased adverse outcomes in patients with acute coronary syndromes. The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated superior net clinical outcomes with similar rates of ischemia and significantly less major bleeding with bivalirudin monotherapy compared with UFH/ENOX plus a glycoprotein (GP) IIb/IIIa inhibitor. It is unknown if these results would be preserved in patients switched from UFH/ENOX to bivalirudin monotherapy.. We compared composite ischemia, major bleeding, and net clinical outcomes at 30 days in patients receiving consistent UFH/ENOX therapy and in those switched at randomization from pre-treatment with UFH/ENOX to bivalirudin monotherapy. We also compared outcomes in patients naive to antithrombin therapy who were randomized to UFH/ENOX or bivalirudin monotherapy.. Two thousand one hundred thirty-seven patients received consistent UFH/ENOX (UFH n = 1,294, ENOX n = 843), and 2,078 patients pre-treated with UFH/ENOX were switched to bivalirudin. Patients switching to bivalirudin had similar rates of ischemia (6.9% vs. 7.4%, p = 0.52), less major bleeding (2.8% vs. 5.8%, p < 0.01), and improved net clinical outcomes (9.2% vs. 11.9%, p < 0.01) than those on consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy who were administered bivalirudin (n = 1,427) had similar rates of ischemia (6.2% vs. 5.5%, p = 0.47), less major bleeding (2.5% vs. 4.9%, p < 0.001), and similar net clinical outcomes (8.0% vs. 9.4%, p = 0.17) compared with naive patients administered UFH/ENOX plus a GP IIb/IIIa inhibitor (n = 1,462).. Switching from UFH/ENOX to bivalirudin monotherapy results in comparable ischemic outcomes and an approximately 50% reduction in major bleeding compared with consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy administered bivalirudin monotherapy had a significant reduction in bleeding and similar rates of ischemia compared with naive patients initiated with UFH or ENOX plus a GP IIb/IIIa inhibitor.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Anticoagulants; Enoxaparin; Female; Heart Conduction System; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Treatment Outcome

At 30-day follow-up, patients with moderate- and high-risk acute coronary syndromes (ACS) undergoing early invasive treatment in the ACUITY trial with bivalirudin monotherapy vs heparin plus glycoprotein (GP) IIb/IIIa inhibitors had noninferior rates of adverse ischemic events with reduced rates of major bleeding. Deferred upstream use of GP IIb/IIIa inhibitors for selective administration to patients undergoing percutaneous coronary intervention (PCI) resulted in a significant reduction in major bleeding, although a small increase in composite ischemia could not be excluded.. To determine 1-year ischemic outcomes for patients in the ACUITY trial.. A prospective, randomized, open-label trial with 1-year clinical follow-up at 450 academic and community-based institutions in 17 countries. A total of 13,819 patients with moderate- and high-risk ACS undergoing invasive treatment were enrolled between August 23, 2003, and December 5, 2005.. Patients were assigned to heparin plus GP IIb/IIIa inhibitors (n = 4603), bivalirudin plus GP IIb/IIIa inhibitors (n = 4604), or bivalirudin monotherapy (n = 4612). Of these patients, 4605 were assigned to routine upstream GP IIb/IIIa administration and 4602 were deferred to selective GP IIb/IIIa inhibitor administration.. Composite ischemia (death, myocardial infarction, or unplanned revascularization for ischemia) at 1 year.. Composite ischemia at 1 year occurred in 15.4% of patients assigned to heparin plus GP IIb/IIIa inhibitors and 16.0% assigned to bivalirudin plus GP IIb/IIIa inhibitors (compared with heparin plus GP IIb/IIIa inhibitors, HR, 1.05; 95% CI, 0.95-1.16; P = .35), and 16.2% assigned to bivalirudin monotherapy (HR, 1.06; 95% CI, 0.95-1.17; P = .29). Mortality at 1 year occurred in an estimated 3.9% of patients assigned to heparin plus GP IIb/IIIa inhibitors, 3.9% assigned to bivalirudin plus GP IIb/IIIa inhibitors (HR, 0.99; 95% CI, 0.80-1.22; P = .92), and 3.8% assigned to bivalirudin monotherapy (HR, 0.96; 95% CI, 0.77-1.18; P = .67). Composite ischemia occurred in 16.3% of patients assigned to deferred use compared with 15.2% of patients assigned to upstream administration (HR, 1.08; 95% CI, 0.97-1.20; P = .15).. At 1 year, no statistically significant difference in rates of composite ischemia or mortality among patients with moderate- and high-risk ACS undergoing invasive treatment with the 3 therapies was found. There was no statistically significant difference in the rates of composite ischemia between patients receiving routine upstream administration of GP IIb/IIIa inhibitors vs deferring their use for patients undergoing PCI.. clinicaltrials.gov Identifier: NCT00093158.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

Topics: Acute Coronary Syndrome; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Patients with chronic dialysis dependency undergoing percutaneous coronary intervention (PCI) are at a greater risk of hemorrhagic and ischemic events. Due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. Bivalirudin has been associated with fewer hemorrhagic complications than unfractionated heparin (UFH) in patients undergoing PCI. We evaluated major adverse cardiac event (MACE) and hemorrhagic event rates for an antithrombotic regimen using bivalirudin or UFH during PCI in acute coronary syndrome (ACS) patients with chronic dialysis dependency.. A retrospective study was performed, including 211 patients on dialysis undergoing PCI due to ACS from January 2014 to April 2019 at the China-Japan Friendship Hospital. Patients were divided into 2 groups based on anticoagulation regimen: the bivalirudin group (86 cases) or the UFH group (125 cases) during and after PCI. Statistical analyses were used to compare MACE and hemorrhagic events between groups at 30 days after PCI.. No patients experienced stent thrombosis within 30 days after PCI regardless of anticoagulant. There was no difference in the incidence of MACE in the bivalirudin group compared with the UFH group (6.98% vs 8.80%, respectively; P>.05). The rate of hemorrhagic events in the bivalirudin group was significantly lower than in the UHP group (5.81% vs 18.4%, respectively; P<.05), particularly for rates of mild bleeding (4.65% vs 15.2%, respectively; P<.05). There were no significant differences in rates of severe bleeding between the bivalirudin and UFH groups (1.16% vs 4.00%, respectively; P>.05), although fewer severe hemorrhagic events occurred in the bivalirudin group.. Bivalirudin was associated with fewer bleeding events following PCI in individuals with end-stage renal disease on dialysis.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Renal Dialysis; Retrospective Studies

There are limited data on bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) with positive biomarkers of myocardial necrosis (troponin and/or creatine kinase-myocardial band isoenzyme). We sought to evaluate the safety and efficacy of bivalirudin monotherapy in patients with positive biomarkers from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.. We compared the net adverse clinical events [composite ischemia - (death, myocardial infarction, or unplanned ischemic revascularization) - or noncoronary artery bypass graft surgery (CABG)-related major bleeding] among patients with biomarker-positive NSTE-ACS in the ACUITY trial overall and by antithrombotic strategy.. Among 13 819 patients with NSTE-ACS enrolled in ACUITY, 4728 patients presented with positive biomarkers and underwent an early invasive strategy. Of those, 1547 were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), 1555 to bivalirudin plus GPI, and 1626 to bivalirudin monotherapy. Compared with biomarker-negative patients, biomarker-positive patients had higher 30-day rates of net adverse clinical events (14.0 vs. 12.4%; P = 0.04), all-cause death (1.3 vs. 0.5%; P = 0.001), cardiac death (1.1 vs. 0.5%; P = 0.005), and non-CABG-related major bleeding (6.5 vs. 5.2%, P = 0.03). At 30 days, bivalirudin monotherapy was associated with significantly less non-CABG-related major bleeding (bivalirudin monotherapy 4.1% vs. bivalirudin plus GPI 8.4% vs. heparin plus GPI 7.1%) with comparable rates of composite ischemia (bivalirudin monotherapy 9.2% vs. bivalirudin plus GPI 9.9% vs. heparin plus GPI 8.4%). In a multivariable model, bivalirudin monotherapy was associated with a significant reduction in non-CABG-related major bleeding but was not associated with an increased risk of death, myocardial infarction, unplanned revascularization or stent thrombosis.. Compared with heparin plus GPI or bivalirudin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding at 30 days among patients with NSTE-ACS and positive biomarkers.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Creatine Kinase, MB Form; Enoxaparin; Female; Hirudins; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Partial Thromboplastin Time; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Recombinant Proteins; Troponin

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

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

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

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

Topics: Acute Coronary Syndrome; Anticoagulants; Heparin; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

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

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

Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non-ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.

Topics: Acute Coronary Syndrome; Aged; Blood Coagulation; Blood Platelets; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation; Recombinant Proteins; Risk Factors; Thrombosis

Topics: Acute Coronary Syndrome; Anticoagulants; Fibrinolytic Agents; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Stents

Topics: Acute Coronary Syndrome; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

Topics: Acute Coronary Syndrome; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Topics: Acute Coronary Syndrome; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Topics: Acute Coronary Syndrome; Anticoagulants; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

Topics: Acute Coronary Syndrome; Fibrinolytic Agents; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

Dual antiplatelet therapy (DAPT) varies after placement of drug-eluting stents (DES) in patients presenting with acute coronary syndromes (ACS). Our aim was to study patient characteristics and predictors of switching, in-hospital or at discharge, from clopidogrel (CLO) to ticagrelor (TIC) or vice versa.. The study population included patients with ACS who had DES and initially received either CLO or TIC between January 2011 and December 2017. Patients were divided into 4 groups based on initial DAPT choice and whether DAPT was switched in-hospital or during discharge. Clinical outcomes of interest were bleeding events, need for anticoagulation, and need for in-hospital coronary artery bypass graft (CABG).. We identified 2837 patients who received DES and started on DAPT. DAPT switch from 1 P2Y12 inhibitor to another occurred in 9%, either in-hospital or at discharge. Of 1834 patients started on CLO, 112 were switched to TIC. Of 1003 patients started on TIC, 142 were switched to CLO. The need for in-hospital CABG was 7.8% in the TIC-CLO group compared to none in the CLO-TIC group (p = 0.002). Adjusted for covariates, the TIC-CLO group was 3 times more likely to need anticoagulation with warfarin than the CLO-CLO group (p < 0.001) and over 5 times more likely than the CLO-TIC group and the TIC-TIC group (p < 0.005 for both).. Switching from 1 generation P2Y12 inhibitor to another does occur in ACS patients. Clinical needs such as in-hospital CABG or oral anticoagulation upon discharge are real and dictate the switch from TIC to CLO.. A single-center observational study of 2837 patients with acute coronary syndromes treated with drug-eluting stents found that some do get switched from one generation P2Y12 inhibitor to another. The switch from clopidogrel to ticagrelor is driven by clinical needs such as in-hospital coronary artery bypass grafting or the need for oral anticoagulation upon discharge.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Drug Substitution; Drug-Eluting Stents; Female; Follow-Up Studies; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Retrospective Studies; Thrombolytic Therapy; Treatment Outcome; Warfarin

Anti-platelet and anti-coagulant adjunctive therapies are associated with a clinically significant increased risk of major bleeding. We retrospectively assessed in-hospital major adverse clinical events (MACE) and major bleeding in patients undergoing percutaneous coronary intervention (PCI) who received either unfractionated heparin (UFH) or bivalirudin.. Consecutive patients undergoing PCI for acute coronary syndrome (ACS) at Fremantle Hospital from August 2008 to December 2013 were identified. Patients received dual antiplatelet therapy (DAPT), with either UFH (50-100IU/kg) or bivalirudin (bolus 0.75mg/kg and infusion 1.75mg/kg/hr). Adjunctive glycoprotein IIb/IIIa (GPIIbIIIa) antagonist use was at the operator's discretion. In-hospital events were identified from case notes and PCI database review.. Of 3371 patients identified, 1740 received UFH and 1631 received bivalirudin. The two groups were similar with respect to age, 62.5 SD 12.1 yrs vs. 62.8 SD 12.2 yrs, (p=0.575) female gender, 24% vs. 26% (p=0.10), current smokers, 66% vs. 70% (p=0.53), diabetes, 25% vs. 26% (p=0.62) and the use of DAPT (p=ns). Presentation with ST-segment-elevation myocardial infarction (STEMI) was significantly higher in the UFH group (28% vs. 19%, p<0.001). The use of transfemoral arterial access was similar (93% UFH vs. 92% bivalirudin) (p=0.41). More patients received GPIIb/IIIa antagonist in the UFH group (30% vs. 3%; p <0.001). There was no difference in pre-discharge acute stent thrombosis (<24hours) occurring in 1.0% with UFH vs. 0.5% with bivalirudin (p=0.20). The equipoise on the outcomes of stent thrombosis persisted after multivariate adjustment for difference in rates of STEMI. In-hospital BARC Type 1-3 major bleeding occurred in 3.7% in the UFH group vs. 2.9% in the bivalirudin group (p=0.20).. Unfractionated heparin compared with bivalirudin was not associated with a higher incidence of in-hospital MACE or major bleeding in a cohort with overall high rates of transfemoral access, despite significantly higher use of GPIIb/IIIa antagonists in the UFH group.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Recombinant Proteins; Retrospective Studies; Survival Rate; Treatment Outcome

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

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

Topics: Acute Coronary Syndrome; Ambulances; Angiography; Follow-Up Studies; Glycoproteins; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Our aim was to report on a survey initiated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) collecting the opinion of the cardiology community on the invasive management of acute coronary syndrome (ACS), before and after the MATRIX trial presentation at the American College of Cardiology (ACC) 2015 Scientific Sessions.. A web-based survey was distributed to all individuals registered on the EuroIntervention mailing list (n=15,200). A total of 572 and 763 physicians responded to the pre- and post-ACC survey, respectively. The radial approach emerged as the preferable access site for ACS patients undergoing invasive management with roughly every other responder interpreting the evidence for mortality benefit as definitive and calling for a guidelines upgrade to class I. The most frequently preferred anticoagulant in ACS patients remains unfractionated heparin (UFH), due to higher costs and greater perceived thrombotic risks associated with bivalirudin. However, more than a quarter of participants declared the use of bivalirudin would increase after MATRIX.. The MATRIX trial reinforced the evidence for a causal association between bleeding and mortality and triggered consensus on the superiority of the radial versus femoral approach. The belief that bivalirudin mitigates bleeding risk is common, but UFH still remains the preferred anticoagulant based on lower costs and thrombotic risks.

Topics: Acute Coronary Syndrome; Adult; Antithrombins; Attitude of Health Personnel; Cardiology; Femoral Artery; Hirudins; Humans; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Radial Artery; Recombinant Proteins; Societies, Medical; Surveys and Questionnaires

Topics: Acute Coronary Syndrome; Antithrombins; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

The CARTAGOMAX study assessed the safety and efficacy of bivalirudin during real-world cardiac intervention. This was a single-center prospective study. Patients with acute coronary syndrome undergoing percutaneous coronary intervention were anticoagulated with bivalirudin alone or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor. Propensity score matching was performed to control for baseline imbalances and yielded 1168 patients. There was lower incidence of the composite outcome of death from any cause or major bleeding at 30 days (P = 0.005), 6 months (P = 0.005), and 12 months (P = 0.001) of follow-up in the bivalirudin group, compared with the heparin plus glycoprotein inhibitor group. The administration of bivalirudin was associated with lower rate of all-cause mortality at 1 year of follow-up (P = 0.009). The incidence of major bleeding was lower in the bivalirudin group at 1, 6, and 12 months of follow-up (P = 0.002, P = 0.013 and P = 0.017, respectively). The incidence of stroke and reinfarction were similar between groups during follow-up. The rate of stent thrombosis were slightly higher in the bivalirudin group, without reaching statistical significance at 1 and 12 months of follow-up (P = 0.06, P = 0.04, P = 0.07 at 1, 6, and 12 months, respectively). The CARTAGOMAX study found that the use of bivalirudin during percutaneous coronary intervention was associated with lower incidence of the composite outcome of death from any cause or major bleeding during follow-up. The use of bivalirudin was associated with similar rates of stroke, reinfarction, and stent thrombosis compared with heparin plus glycoprotein inhibitor. Bivalirudin proved to be a safe and effective anticoagulant during percutaneous coronary intervention.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Female; Follow-Up Studies; Hirudins; Humans; Intraoperative Care; Longitudinal Studies; Male; Middle Aged; Mortality; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Treatment Outcome

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Treatment Outcome

In a retrospective analysis of a prospective single center registry we compared the use of bivalirudin, unfractionated heparin (UFH) monotherapy, UFH + abciximab in 1240 consecutive patients with acute coronary syndrome (ACS) undergoing stent implantation.. Bivalirudin was associated with tendentially reduced in-hospital minor or major bleeding rates compared to UFH monotherapy (5.9 % vs. 9.4 % adjusted odds ratio (OR) 0.82, 95 % confidence interval CI 0.45-1.51, p = 0.53) and compared to the pooled UFH group (5.9 % vs. 11.9 %, adjusted OR 0.62, 95 % CI 0.36-1.08, p = 0.09) but with significantly lower bleeding hazards compared to UFH + abciximab (5.9 % vs. 16 %, adjusted OR 0.41, 95 % CI 0.22-0.78, p < 0.01). After 3 years of follow-up, adjusted cardiovascular mortality rates were similar between all groups, particularly between bivalirudin vs. UFH monotherapy (hazard ratio HR 1.12, 95 % CI 0.58-2.16, p = 0.73) and vs. UFH + abciximab (HR 0.91, 95 % CI 0.40-2.10, p = 0.83). Acute or subacute stent thrombosis occurred at a rate of 0.8 % with no significant differences between the groups.. This retrospective analysis in a real world situation of medium to high-risk ACS patients undergoing invasive revascularization confirmed the results of most large-scale randomized trials by demonstrating reduced bleeding rates in favor of bivalirudin vs. UFH + GPI but with no significant differences between treatment strategies for long-term all-cause and cardiovascular mortality.

Topics: Acute Coronary Syndrome; Antithrombins; Austria; Combined Modality Therapy; Female; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Prevalence; Recombinant Proteins; Retrospective Studies; Risk Factors; Survival Rate; Treatment Outcome

The results of randomized trials and observational studies make a strong argument for the use of bivalirudin rather than heparin plus systematic glycoprotein (GP) IIb/IIIa inhibitors for the great majority of patients undergoing percutaneous coronary interventions (PCI). However, there is no doubt that the benefit observed with bivalirudin was achieved because of the major bleeding complications with heparin plus GP IIb/IIIa inhibitors. Therefore, if we diminish bleeding complications by eliminating the systematic utilization of GP IIb/IIIa inhibitors, there would be a lesser benefit with the use of bivalirudin. When this latter drug was compared with unfractionated heparin alone there was no benefit in ischemic complications but a decrease in major bleeding complications with bivalirudin. However, a very recent meta-analysis shed more insights on the utilization of bivalirudin versus heparin regimens during PCI. Findings from this meta-analysis suggest that routine use of bivalirudin offers little advantage over heparin among PCI patients. In a detailed analysis of some randomized trials and observational studies with bivalirudin in non-ST-segment elevation acute coronary syndrome patients done by myself and published almost 4 years ago in this journal, I rendered some reflections on the future widespread use of bivalirudin. "In the setting of PCI and in the absence of GP IIb/IIIa inhibitors, bivalirudin did not offer any beneficial effect in the incidence of the composite end points when compared with heparin. For now, in real world practice, one would probably choose a well-known cheaper drug that has already passed the test of time, heparin. There may be reinforcement in the sole utilization of heparin confining GP IIb/IIIa inhibitors and other intravenous antithrombotics to bailout therapy for periprocedural PCI complications in acute coronary syndrome patients." Therefore, is it the beginning of a new era with bivalirudin or is it a welcome back to an old friend, heparin? Indeed, after more than two decades, it is always good to welcome back an old friend, unfractionated heparin.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

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

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

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

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

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

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

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

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

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

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

Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to other anticoagulant in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). This study analyzed the cost/efficacy profile of bivalirudin-based anticoagulation strategy versus non bivalirudin-based anticoagulant strategy without use of GP IIb/IIIa inhibitors in routine clinical practice. From January 2009 to December 2010, 216 patients who underwent PCI for ACS at hospital Georges-Pompidou without GP IIb/IIIa inhibitors were studied. Of these patients, 24 (11%) received bivalirudin and 192 (88%) received others anticoagulants (mainly unfractionated heparin or low molecular weight heparin). Ischemic events and bleeding or transfusion were slightly lower in bivalirudin group (0 vs. 4.2%, P=0.60 and 4.2 vs. 8.9%, P=0.70, respectively). In spite of a higher cost of the medication, the overall cost of the bivalirudin strategy was slightly lower (9167±3688 € vs. 14,016±14,749 €, P=0.23), in relation with a shorter average duration of the hospital stay. In conclusion, in this limited, single-center, population of patients with ACS, the clinical efficacy and safety of bivalirudin appeared at least as good as that of reference anticoagulants in real world clinical practice, with no increase in overall costs.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Cost-Benefit Analysis; Drug Costs; Female; Heparin; Hirudins; Hospitals, University; Humans; Length of Stay; Male; Middle Aged; Paris; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Registries; Treatment Outcome

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

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

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Antithrombins; Hirudins; Humans; Leukemia, Myeloid, Acute; Male; Peptide Fragments; Recombinant Proteins; Stents

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

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

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

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

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

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

This study sought to assess the cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor (GPI) in thienopyridine-treated non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing early or urgent invasive management, from a United Kingdom National Health Service perspective.. A decision-analytic model with lifelong time horizon was populated with event risks and resource use parameters derived from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial raw data. In a parallel analysis, key comparator strategy inputs came from Global Registry of Acute Coronary Events (GRACE) patients enrolled in the United Kingdom. Upstream and catheter laboratory-initiated GPI were assumed to be tirofiban and abciximab, respectively. Life expectancy of first-year survivors, unit costs, and health-state utilities came from United Kingdom sources. Costs and effects were discounted at 3.5%. Incremental cost-effectiveness ratios (ICERs) were expressed as cost per quality-adjusted life year (QALY) gained.. Higher acquisition costs for bivalirudin were partially offset by lower hospitalization and bleeding costs. In the ACUITY-based analysis, per-patient lifetime costs in the bivalirudin and heparin plus GPI strategies were £10,903 and £10,653, respectively. Patients survived 10.87 and 10.82 years on average, corresponding to 5.96 and 5.93 QALYs and resulting in an ICER of £9,906 per QALY gained. The GRACE-based ICER was £12,276 per QALY gained. In probabilistic sensitivity analysis, 72.1% and 67.0% of simulation results were more cost-effective than £20,000 per QALY gained, in the ACUITY-based and GRACE-based analyses, respectively. Additional scenario analyses implied that greater cost-effectiveness may be achieved in actual clinical practice.. Treating NSTE-ACS patients undergoing invasive management with bivalirudin is likely to represent a cost-effective option for the United Kingdom, when compared with the current practice of using heparin and a GPI.

Topics: Abciximab; Acute Coronary Syndrome; Antibodies, Monoclonal; Anticoagulants; Cost-Benefit Analysis; Decision Trees; Drug Therapy, Combination; Female; Health Care Costs; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Models, Econometric; Myocardial Revascularization; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Quality-Adjusted Life Years; Recombinant Proteins; Survival Analysis; Tirofiban; Tyrosine; United Kingdom

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

Topics: Acute Coronary Syndrome; Aged, 80 and over; Antithrombins; Combined Modality Therapy; Coronary Angiography; Coronary Artery Bypass; Echocardiography; Embolic Protection Devices; Graft Occlusion, Vascular; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Saphenous Vein; Thrombectomy; Venous Thrombosis

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

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

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Enoxaparin; Fibrinolytic Agents; Heparin; Hirudins; Humans; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

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

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

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

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

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

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

Topics: Acute Coronary Syndrome; Heparin; Hirudins; Humans; Peptide Fragments; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Treatment Outcome

Anticoagulant therapy is a major component in the management of acute coronary syndromes (ACS). Four anticoagulant agents are currently commercially available for ACS, namely unfractionated heparin (UFH), enoxaparin, bivalirudin and fondaparinux. We describe the advantages of fondaparinux and the reasons that have hampered its uptake into routine management of ACS. Fondaparinux was shown to be efficacious in the prevention of deep vein thrombosis vs low-molecular-weight heparins, while in the setting of venous thrombo-embolic disease, it was shown to be noninferior to enoxaparin and UFH. Two pivotal studies have demonstrated the efficacy of fondaparinux as an anticoagulant in the setting of ACS, namely OASIS-5 in non-ST elevation ACS, and OASIS-6 in ST elevation myocardial infarction (MI). In OASIS-5, fondaparinux was shown to be noninferior to enoxaparin in terms of death, MI or refractory ischemia at 9 days. Furthermore, a 50% reduction in bleeding complications was obtained with fondaparinux vs enoxaparin, leading to a risk reduction for death. In OASIS-6, fondaparinux was shown to be superior to the comparator (UFH or placebo). European and North American guidelines give fondaparinux a Grade 1A and 1B recommendation respectively, but uptake of fondaparinux in routine practice has been slow. We explore reasons for this, such as prevailing doubts about the efficacy of fondaparinux in the setting of angioplasty, the problem of catheter thrombosis, and the lack of antidote in case of bleeding complications. With the exception of primary angioplasty, fondaparinux is as effective as enoxaparin or UFH, but is also associated with a considerable reduction in bleeding complications, and thus, an undeniable net clinical benefit.

Topics: Acute Coronary Syndrome; Anticoagulants; Catheterization; Enoxaparin; Fondaparinux; Hirudins; Humans; Peptide Fragments; Polysaccharides; Recombinant Proteins; Thrombosis

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

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

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

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

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

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

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

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

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

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

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials, Phase II as Topic; Cyclic N-Oxides; Drug Monitoring; Heparin; Hirudins; Humans; Metabolic Clearance Rate; Patient Selection; Peptide Fragments; Pyridines; Recombinant Proteins

Topics: Acute Coronary Syndrome; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Membrane Glycoprotein IIb; 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

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

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

Bivalent direct thrombin inhibitors reduce ischemic risk compared to heparin. Results from randomized, double-blind clinical trials have demonstrated that bivalirudin is superior to heparin alone and as effective as heparin plus routine glycoprotein (GP) IIb/IIIa therapy for the prevention of ischemic events with a statistically significant reduction in the rate of in-hospital major bleeding.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Clinical Trials as Topic; Coronary Disease; Costs and Cost Analysis; Diabetic Angiopathies; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Risk Assessment; Treatment Outcome