thienopyridine and Angina--Unstable

The vast majority of acute coronary syndrome (ACS) trials conducted over the past two decades support the view that women have persistently higher mortality and morbidity despite the introduction of new medical therapies and devices. Even after adjustment for older age, higher prevalence of diabetes, hypertension, heart failure, smaller vessel size, and late presentation, some studies still point to a persistent sex disadvantage. Even in contemporary practice, women continue to have longer delays in presentation and treatment. Selection bias in unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) trials allows inclusion of large numbers of women with clinically insignificant coronary disease and may mistakenly shift results toward apparent benefit of a less aggressive approach. This bias causes further difficulty in determining efficacy and safety of new antithrombotic agents such as direct thrombin inhibitors and glycoprotein IIb/IIa inhibitors across the spectrum of ACS. In trials of UA/NSTEMI, use of objective evidence of ischemia such as elevated troponin levels, would greatly assist the determination of efficacy and benefit in women. Enrollment of more women in clinical trials and timely sex-specific analysis would promote a better understanding of the role of female gender in ACS and would facilitate better care of all patients.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Artery Bypass; Female; Fibrinolytic Agents; Humans; Myocardial Infarction; Myocardial Revascularization; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Stents; Syndrome; Thrombin; Ticlopidine; Women's Health

The recognition that thrombosis is fundamental to acute coronary syndromes (ACS) has inspired the development of novel therapies to inhibit platelet aggregation and thrombus formation. Several recent advances have been made in the management of patients with non-ST-segment elevation ACS (NSTE ACS) to improve early and late clinical outcomes. The research efforts leading to these improvements in care have focused on antiplatelet and anticoagulant therapies coupled with early invasive treatment options. In particular, ongoing clinical trials seek to refine treatment strategies for patients relative to individual risk presentation, the availability of facilities for invasive procedures, and the timing of revascularization. However, even despite the proven efficacy of currently available therapies to reduce the occurrence of death and/or myocardial infarction, still many eligible patients with high-risk NSTE ACS do not receive such treatments. This review provides a pathophysiologic rationale for antithrombotic therapies in ACS, examines the results of recent trials, and presents future directions for clinical investigation.

Topics: Angina, Unstable; Aspirin; Clinical Trials as Topic; Coronary Artery Disease; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Thrombolytic Therapy

Topics: Acute Disease; Angina, Unstable; Anticoagulants; Aspirin; Clinical Trials as Topic; Coronary Disease; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Syndrome

Recent advances in our understanding of the role of the platelet in the atherosclerotic process beyond the acute formation of arterial blood clots, such as inflammation, have highlighted the role of antiplatelet agents as being much more than just 'blood thinners.' Some of the most important cardiovascular trials performed in the last 20 years have studied antiplatelet therapies. However, despite their long history, current global health implications and proven benefit, there remain substantial gaps in our understanding as to how to best utilize the limited number of antiplatelet agents available. This article will discuss the mechanism of action of the antiplatelet class known as thienopyridines, the pharmacodynamics and pharmacokinetics of the thienopyridine agent clopidogrel (Plavix, Bristol-Myers Squibb and Sanofi Pharmaceuticals) as well as the literature supporting its clinical benefits and areas of ongoing research that will help clarify the optimal utilization of clopidogrel for the treatment of cardiovascular disease.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Arteriosclerosis; Aspirin; Clinical Trials as Topic; Clopidogrel; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Stents; Ticlopidine; Treatment Outcome; Vascular Diseases

Thienopyridine use, in particular clopidogrel in acute coronary syndromes, has been associated with an improvement in outcome. However, little information is available regarding their bleeding risk when used in combination with other antithrombotic agents and revascularisation.. In a large, multinational, prospective registry, the Global Registry of Acute Coronary Events, the major bleeding rate (using GRACE criteria) of 27,358 patients with unstable angina or non-ST-elevation myocardial infarction was recorded during index admission. The interaction of thienopyridines on major bleeding with other antithrombotic agents and with revascularisation was analysed.. The 11,478 patients who received thienopyridines during hospitalisation experienced a significant increase in major bleeding (2.8% with thienopyridines, 2.2% without thienopyridines; p=0.002). No significant interaction with glycoprotein IIb/IIIa inhibitors and thienopyridines was seen with regard to bleeding. Thienopyridines with unfractionated heparin did not alter bleeding risk, but thienopyridines with low molecular weight heparin was associated with a significant excess of bleeding (2.1% with thienopyridines, 1.3% without thienopyridines; p=0.004). There was no significant difference in major bleeding with thienopyridines in patients who did or did not undergo revascularisation.. Major bleeding was increased in patients receiving thienopyridines. No increase in bleeding risk was seen in patients having revascularisation.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Bypass; Electrocardiography; Female; Hemorrhage; Hospital Mortality; Humans; International Cooperation; Male; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Revascularization; Probability; Prognosis; Prospective Studies; Pyridines; Registries; Risk Assessment; Severity of Illness Index; Survival Analysis; Thromboembolism

Topics: Angina, Unstable; Cardiac Catheterization; Clinical Trials as Topic; Clopidogrel; Coronary Angiography; Data Interpretation, Statistical; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Stents; Syndrome; Ticlopidine; Time Factors

Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb/IIIa inhibitors in higher risk patients with an acute coronary syndrome (ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070 (62.7%) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb/IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy with aspirin, thienopyridines, and glycoprotein IIb/IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and/or percutaneous coronary intervention, as well as high-risk patient features. Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization.

Topics: Aged; Angina, Unstable; Drug Therapy, Combination; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines

Ticlopidine or clopidogrel combined with aspirin decrease major cardiac events (Mace) after PTCA with stent implantation. It has not be proven yet that pretreatment by T or C was superior to conventional post-treatment, especially in unstable patients. The aim of the present study was to determine the influence of thienopyridine pretreatment on the risk of Mace (death, Q wave myocardial infarction, need for repeat PTCA or surgery, angina recurrence, stent thrombosis) during the hospitalization period in a population prospectively included in 2 multicentre registries of patients undergoing placement of a S670 or S7 stent (Medtronic) implanted in native coronary arteries (> or = 3.0 mm). Among the 2929 patients included into the registries, 1205 had unstable angina (41%). 50.2% of the patients were pretreated by T or C (T = 15.7%, C = 34.5%); 85.5% received aspirin before the procedure; definition of pretreatment was the administration of drug at least 6 hours before stent implantation. GPIIb-IIIa antagonists were administered in only 13.9% of patients. Mace were observed in 2% of the patients. Factors correlated with Mace by univariate and multivariate analyses were: age > 73 years (RR: 2.37; 95% CI: 1.05-5.36, P < 0.037), previous myocardial infarction (RR: 2.56; 95% CI: 1.08-6.11, P < 0.034), pretreatment by T or C (RR: 0.389; 95% CI: 0.16-0.95, P < 0.038). In patients who did not receive GPIIb-IIIa antagonists, age > 73, and pretreatment by T or C were the only independent predictors of Mace.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Clopidogrel; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Platelet Aggregation Inhibitors; Premedication; Pyridines; Risk Factors; Stents; Ticlopidine; Time Factors; Treatment Outcome