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Role of Clopidogrel in Managing Atherothrombotic Cardiovascular Disease

Shervin Eshaghian, MD; Sanjay Kaul, MD; Sameer Amin, MD; Prediman K. Shah, MD; and George A. Diamond, MD
[+] Article and Author Information

From the Cedars-Sinai Medical Center and the David Geffen School of Medicine, University of California, Los Angeles, California.


Grant Support: None.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Sanjay Kaul, MD, Division of Cardiology, Room 5536, South Tower, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048; e-mail, kaul@cshs.org.

Current Author Addresses: Drs. Eshaghian, Kaul, Amin, Shah, and Diamond: Division of Cardiology, Room 5536, South Tower, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048.


Ann Intern Med. 2007;146(6):434-441. doi:10.7326/0003-4819-146-6-200703200-00008
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Aspirin is the most widely used antiplatelet agent for preventing and treating vascular events. The thienopyridine derivatives, ticlopidine and clopidogrel, are a suitable alternative in patients who are intolerant to aspirin, and clopidogrel exhibits better tolerability than ticlopidine. The available evidence from randomized trials indicates that dual therapy with clopidogrel and aspirin is modestly but significantly more effective than aspirin in preventing serious vascular events. It is also associated with a favorable benefit–risk profile in patients at high risk (especially in acute coronary syndromes and after stenting). In patients at low risk (stable cardiovascular disease), however, the bleeding risk of dual therapy exceeds its potential benefit. The dose and duration of pretreatment before stenting, the optimal duration of treatment after drug-eluting stent implantation, concurrent administration of platelet glycoprotein IIb/IIIa inhibitors, and the exact mechanism and clinical relevance of clopidogrel resistance are unclear.

Figures

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Figure 1.
Absolute benefit and bleeding hazard of combined treatment with clopidogrel plus aspirin.

Data for the composite efficacy end point of cardiovascular death, nonfatal myocardial infarction, or stroke (treatment benefit) for the 5 major trials at maximum follow-up is plotted on the left ordinate axis as the number of events prevented by treating 1000 patients with clopidogrel plus aspirin. The bleeding hazard is plotted on the right ordinate axis as the number of major bleeding complications (defined by Thrombolysis In Myocardial Infarction criteria) caused by treating 1000 patients. The incidence of cardiovascular risk at maximum follow-up in control participants (treated with aspirin alone) is plotted on the abscissa. CURE = Clopidogrel in Unstable angina to prevent Recurrent ischemic Events; CREDO = Clopidogrel for the Reduction of Events During Observation; CHARISMA = Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance; CLARITY = Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis In Myocardial Infarction; COMMIT = Clopidogrel and Metoprolol in Myocardial Infarction Trial.

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Figure 2.
Comparison of clopidogrel plus aspirin (ASA) versus ASA alone in high-risk patients with cardiovascular disease.

Data for cardiovascular death, nonfatal myocardial infarction, and stroke at maximum follow-up for the 5 major trials are shown as point estimate and 95% CIs. Because of major differences in trial demographic characteristics (acute coronary syndrome, stable cardiovascular disease, and low-risk or high-risk patients), concomitant therapies (medical therapy, percutaneous coronary intervention, and thrombolysis), and duration of follow-up (28 d to 28 mo), a formal meta-analysis was not conducted. However, the results of heterogeneity analysis using the Cochran Q-test (chi-square statistics) and I2 statistic are reported. CURE = Clopidogrel in Unstable angina to prevent Recurrent ischemic Events; CREDO = Clopidogrel for the Reduction of Events During Observation; CHARISMA = Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance; CLARITY = Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis In Myocardial Infarction; COMMIT = Clopidogrel and Metoprolol in Myocardial Infarction Trial.

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