Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation

Abstract

Background Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients. MethodsWe randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months. ResultsThe first primary outcome -a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke -occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome -the first primary outcome or refractory ischemia -occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86, P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.1 percent vs. 1.8 percent, P=0.13) or hemorrhagic strokes. ConclusionsThe antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients HROMBOSIS caused by a ruptured or eroded atherosclerotic plaque is the usual underlying mechanism of acute coronary syndromes. 1 Aspirin and heparin reduce the risk of death from cardiovascular causes, new myocardial infarction, and recurrent ischemia, 2,3 but there is still a substantial risk of such events in both the short term and the long term. Intravenous glycoprotein IIb/IIIa receptor blockers have been shown to reduce the incidence of early events, mainly among patients T who are treated according to an invasive strategy, 4,5 but long-term oral therapy with glycoprotein IIb/IIIa receptor blockers is not beneficial and may even increase mortality. 6 Similarly, continuing treatment with low-molecular-weight heparin beyond one week has not been shown to be effective. 7 Although the longterm use of oral anticoagulants may be useful, no convincing evidence of their benefit is yet available. 8 Therefore, there is a need to reduce further the risk of ischemic events in a broad spectrum of patients both when they first present with acute coronary syndromes and in the long term.The thienopyridine derivatives, ticlopidine and clopidogrel, are antiplatelet agents that inhibit the platelet aggregation induced by adenosin...

Precatheterization Use of P2Y 12 Inhibitors in Non‐ST‐Elevation Myocardial Infarction Patients Undergoing Early Cardiac Catheterization and In‐Hospital Coronary Artery Bypass Grafting: Insights From the National Cardiovascular Data Registry ®

“…Platelet P2Y 12 receptor inhibitors have been a cornerstone of treatment for patients with acute coronary syndrome; both clopidogrel and higher potency P2Y 12 inhibitors (prasugrel and ticagrelor) were shown to significantly reduce the risk of major adverse cardiovascular events 1, 2, 3. Yet, the optimal timing of administration of P2Y 12 inhibitors has been a moving target for patients with non‐ST‐elevation myocardial infarction (NSTEMI).…”

To Pretreat or Not to Pretreat (With Oral P2Y12 Antagonists)? That is the Question

“…Given hematological side effects associated with ticlodipine, clopidogrel, another member of the thienopyridine family, became an attractive alternative. The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial showed a 30% reduction in major adverse cardiovascular events when clopidogrel was added to aspirin for treatment of patients presenting with non‐ST‐segment elevation acute coronary syndrome 4. Additionally, within a subset of patients in the CURE trial who were randomized to pretreatment with clopidogrel, results showed the benefits of clopidogrel within 24 hours of randomization and extending long term, without increased bleeding risk 5, 6.…”

“…As may be expected, the increasing potency of the P2Y12 inhibitors has been accompanied by a higher risk of bleeding, including procedure‐related bleeding. Even when clopidogrel, the least potent of the P2Y12 inhibitors, was added to aspirin in the CURE study, the bleeding risk was significantly higher than with aspirin alone 4. Similarly, with the progressive increase in potency of P2Y12 inhibitors, bleeding risk has increased—compared with clopidogrel, prasugrel caused increased risk of bleeding, including life‐threatening bleeding, and ticagrelor increased the risk of non‐CABG‐related major bleeding 7, 9.…”

“…Patients now frequently undergo coronary angiography within the first 24 to 48 hours of hospitalization; data from the ACTION Registry suggest that ≈60% of patients undergo coronary angiography within 48 hours 18. In this setting, the benefit of pretreatment with P2Y12 therapy before coronary angiography that was observed in the CURE trial, where coronary angiography occurred a median of 10 days from presentation,4 may no longer be directly applicable. A subanalysis of the CURE trial, however, argues against this.…”

Cigarette smoking might weaken the prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction patients

“…Acute myocardial infarction usually occurs as a result of ruptured atherosclerotic plaque, platelet‐mediated thrombosis and prolonged myocardial ischaemia 4, 5. Antiplatelet drug clopidogrel is an appropriate and immediate treatment for AMI, and should be used for long‐term to prevent recurrent ischaemic events 6, 7.…”