Dual antiplatelet therapy in coronary artery disease: A case-based approach
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.
KEY POINTS
- 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.
CASE 1: ST-ELEVATION MI
A 57-year-old farmer in rural Ohio with a history of hypertension and hyperlipidemia presents to the local emergency department 45 minutes after the onset, while he was chopping wood, of dull, aching, substernal chest pain that radiates to his jaw. Electrocardiography reveals 2-mm ST-segment elevation in leads V1 through V6. He is treated with aspirin 162 mg, low-molecular-weight heparin, and tenecteplase.
What would be the value of starting dual antiplatelet therapy with clopidogrel in this patient?
Clopidogrel, aspirin, and fibrinolysis in ST-elevation MI
The CLARITY-TIMI 28 trial (Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis in Myocardial Infarction)9 included 3,491 patients (ages 18 to 75) from 319 international sites. All patients received a fibrinolytic agent, aspirin (162 mg to 325 mg on the first day and 75 mg to 162 mg thereafter), and heparin as part of standard care for acute ST-elevation MI (Table 1). Patients were randomized to receive a 300-mg loading dose of clopidogrel followed by 75 mg daily or placebo within 12 hours of onset of ST-elevation MI. The status of the infarct-related artery was ascertained by protocol-mandated coronary angiography 48 to 192 hours after starting the study medication. The primary end point was the composite of an occluded infarct-related artery on angiography, death from any cause prior to angiography, or recurrent MI prior to angiography.
Significantly fewer patients had an end point event in the clopidogrel group than in the placebo group, 15% vs 21.7% (P < .001), for a relative risk reduction of 31%. There was no significant increase in major or minor bleeding events.
Of note, the CLARITY-TIMI 28 patients were relatively young (average age 57 years) and at low cardiovascular risk (30-day mortality risk < 5%).
The COMMIT trial (Clopidogrel and Metoprolol in Myocardial Infarction)10 consisted of 45,852 patients with suspected acute MI admitted to 1,250 hospitals in China. Each patient received aspirin 162 mg daily plus either clopidogrel 75 mg daily (n = 22,961) or placebo (n = 22,891) for the duration of hospitalization (average 16 days) or 28 days, whichever came first.
The incidence of the primary composite end point of death, reinfarction, or stroke was significantly lower with clopidogrel than with placebo (9.2% vs 10.1%, P = .002). This was regardless of age (the average age was 61, and 26% of patients were older than 70), sex, time to presentation (67% presented within 12 hours), or reperfusion strategy (49% underwent fibrinolysis). The clopidogrel group did not have a significantly higher incidence of bleeding, but patients in this trial did not receive a loading dose of clopidogrel.
Comment. In view of the results of these trials, our 57-year-old patient should start clopidogrel early.
