Dual antiplatelet therapy in coronary artery disease: A case-based approach

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ABSTRACTCurrent guidelines support dual antiplatelet therapy with aspirin and clopidogrel (Plavix) in a number of clinical scenarios, ie, in ST-segment-elevation myocardial infarction (MI), non-ST-elevation MI, and percutaneous coronary intervention. The guidelines are based on strong evidence from several large randomized clinical trials over the last 10 years. The authors present several cases to show how to put this evidence into day-to-day clinical practice.


  • Dual antiplatelet therapy is recommended after ST-elevation MI or non-ST-elevation acute coronary syndromes, with aspirin indefinitely and clopidogrel for up to 1 year.
  • Dual antiplatelet therapy is recommended for at least 1 month after placement of a bare-metal stent and for at least 1 year (or possibly indefinitely) after placement of a drug-eluting stent.
  • There is no compelling indication for clopidogrel in patients with chronic coronary artery disease.
  • Compared with clopidogrel, prasugrel (Effient) is associated with lower rates of MI, urgent target-vessel revascularization, and in-stent thrombosis, but at the cost of a higher risk of major bleeding.



Plaque rupture and thrombosis play central roles in the genesis of acute coronary syndrome. Aspirin has long been the preventive agent of choice. But dual antiplatelet therapy with aspirin plus clopidogrel (Plavix) is warranted in many patients to further reduce their risk of future cardiovascular events.

Although dual antiplatelet therapy is usually started by a subspecialist, the primary care physician is often the one who ensures that the patient remains compliant with it in the long term. A review of the seminal published data is helpful in understanding the rationale behind dual antiplatelet therapy and its risks and benefits.

In the mid-1990s, the thienopyridine ticlopidine (Ticlid) was found to significantly decrease the number of deaths, target-lesion revascularizations, and myocardial infarctions (MIs) in the 30 days following stent placement. 1 However, 2% to 3% of patients experienced neutropenia2 and thrombotic thrombocytopenic purpura with this drug,3 leading to the use of clopidogrel, another agent in the same class. Over the past decade, a large body of evidence has established the usefulness of clopidogrel in a number of clinical settings.

In this paper we review the current use of clopidogrel in ST-elevation MI, non-ST-elevation acute coronary syndromes, and percutaneous coronary intervention, and discuss the landmark trials that are the basis for the treatment guidelines published jointly by the American College of Cardiology (ACC) and the American Heart Association (AHA).4–6 We also briefly discuss the use of prasugrel (Effient), the newest antiplatelet agent to gain approval from the US Food and Drug Administration (FDA).


Clopidogrel, a prodrug, is converted into its active form in the liver.7 It then irreversibly binds to the platelet P2Y12 receptor and inhibits adenosine diphosphate-induced platelet aggregation.

The CAPRIE trial8 (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) provided the data on the basis of which clopidogrel was approved by the FDA in 1998 (Table 1). In this trial, 19,185 patients with recent ischemic stroke, MI, or symptomatic peripheral arterial disease were randomized to receive clopidogrel or aspirin and were followed for 1 to 3 years.

Those treated with clopidogrel had an annual risk of ischemic stroke, MI, or vascular death of 5.32%, compared with 5.83% in the aspirin group, for a statistically significant 8.7% relative risk reduction (P = .043). The observed frequency of neutropenia (neutrophils < 1.2 × 109/L) was 0.10% with clopidogrel vs 0.17% with aspirin. This study showed clopidogrel to be an effective alternative in patients who cannot tolerate aspirin.


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