Dual Antiplatelet Therapy for Prevention of Recurrent Ischemic Events

Jean Nappi, PharmD, Fccp, Bcps; Robert Talbert, PharmD, Fccp, Bcps

Disclosures

Am J Health Syst Pharm. 2002;59(18) 

In This Article

Acute Coronary Syndrome and MI Trials

An open-label clinical trial was conducted to compare the effects of aspirin 50 mg/day plus ticlopidine 200 mg/day, aspirin 50 mg/day plus dipyridamole 150 mg/day, and each agent as monotherapy (aspirin 50 mg/day, ticlopidine 200 mg/day, dipyridamole 150 mg/day) versus no antiplatelet therapy in preventing recurrent MI.[78] Of the 1083 patients enrolled, 618 patients received one of the antiplatelet regimens on the basis of prescriber preference and patient tolerance, while 465 patients did not receive any antiplatelet therapy. Patients treated with combined therapy had substantially fewer cardiac events than those patients receiving monotherapy.

In 2000, the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial evaluated the efficacy and safety of combination antiplatelet therapy in 12,562 patients with acute coronary syndrome without ST-segment elevation.[87] The first primary outcome was the composite of cardiovascular death, nonfatal MI, and stroke. The second primary outcome was the composite of the first primary out-come and refractory ischemia. At the 12-month follow-up, a 20% reduction in the risk of the primary out-come with clopidogrel in combination with aspirin was found when compared with placebo and aspirin (9.3% versus 11.4%, respectively) (p < 0.001) (Figure 2).[79] There was a 14% relative-risk reduction in the second primary outcome in the clopidogrel group compared with the placebo group (16.5% versus 18.8%, respectively) (p < 0.001). These benefits were consistent among all patient subgroups and were sustained over time in patients followed for 3-12 months (average of 9 months). Major bleeding (defined as disabling bleeding, intraocular bleeding leading to loss of vision, or bleeding requiring the transfusion of at least two units of blood) occurred in significantly more patients receiving clopidogrel in combination with aspirin (3.7%) than in those receiving placebo with aspirin (3.7% versus 2.7%, respectively) (p = 0.001).[79,87] The occurrence of life-threatening bleeding (defined as a bleeding episode that [1] was fatal or led to a reduction in the hemoglobin level of at least 5 g/dL or to substantial hypotension requiring the use of intravenous inotropic agents, [2] necessitated a surgical intervention, [3] was a symptomatic intracranial hemorrhage, or [4] necessitated the transfusion of four or more units of blood) and hemorrhagic stroke did not differ substantially between the groups ( Table 4G ).[79]

A subgroup of 2658 patients enrolled in the CURE trial received percutaneous coronary intervention (PCI). Pretreatment with clopidogrel and aspirin resulted in a 30% reduction (6.4% with placebo versus 4.5% with clopidogrel) in the composite endpoint of cardiovascular death, MI, and urgent revascularization from the time of PCI to 30 days. The advantage of combination therapy was maintained but did not increase with long-term treatment.[88]

The findings of the CURE and PCI-CURE trials have been incorporated into the recently revised American College of Cardiology/American Heart Association Guideline Update for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction.[89] These guidelines now recom-mend that, in patients with unstable angina and NSTEMI with whom a noninterventional approach is taken, clopidogrel and aspirin therapy should be initiated at admission to the hospital and continued for at least one month. In those patients with unstable angina and NSTEMI who are undergoing PCI, pretreatment with aspirin and clopidogrel, followed by at least one month of combination oral antiplatelet therapy, is currently recommended. In those clopidogrel-treated patients who will need coronary artery bypass grafting, the drug should be withheld for five to seven days to minimize the risk of bleeding.

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