Background: American and European cardiology societies recommend six to 12 months of dual-antiplatelet therapy with aspirin and clopidogrel (Plavix) after drug-eluting stent placement to prevent late stent thrombosis. The data used to support these guidelines, however, are derived from older observational studies that included only patients who received clopidogrel before stenting. Because the optimal duration and risk-benefit ratio of dual-antiplatelet therapy are not known, Valgimigli and colleagues compared outcomes with six and 24 months of dual-antiplatelet therapy in patients receiving drug-eluting or bare-metal stents.

The Study: The Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study was a multi-center, prospective, open-label trial in which patients were randomly assigned to a bare-metal stent or one of three U.S. Food and Drug Administration–approved drug-eluting stents. Patients were screened for inclusion between 2006 and 2008. Those 18 years and older with chronic stable coronary artery disease or acute coronary syndromes were eligible for inclusion if they had at least one vessel appropriate for stenting. Inclusion criteria were broad to reflect clinical practice, and exclusions were limited to allergy to aspirin or clopidogrel, planned surgery within 24 months of stenting, need for oral anticoagulation, history of bleeding diathesis, active bleeding in the preceding six months, pregnancy, or life expectancy of less than 24 months.

All patients received loading doses of aspirin and clopidogrel, then 80 to 160 mg of aspirin and 75 mg of clopidogrel daily. After 30 days, patients were randomized to receive six or 24 months of aspirin and clopidogrel. Participants followed up for study visits after 30 days, then every six months for up to two years for clinical examination, electrocardiography, and adherence monitoring. Additionally, nurses contacted participants monthly. The primary end point was death from any cause, nonfatal myocardial infarction, or cerebrovascular accident. The key safety end point was bleeding rates using Thrombolysis In Myocardial Infarction criteria and the BleedScore.

Results: Of the 2,013 patients recruited, 1,970 patients were randomized to six or 24 months of treatment. The two groups had similar baseline characteristics and included similar numbers of each stent type. The median age was 69 years; approximately 25 percent of patients had diabetes mellitus or previous myocardial infarction, and two-thirds of patients presented with acute coronary syndrome. There was no difference between the groups in all-cause mortality, cardiovascular death, nonfatal myocardial infarction or stroke, or stent thrombosis. At two years, the event rate for the primary end point was 10.1 percent for the 24-month treatment group and 10.0 percent in the six-month treatment group. However, there was an approximately twofold increase in bleeding complications requiring medical or surgical treatment or transfusion in the 24-month treatment group.

Conclusion: Extending clopidogrel therapy beyond six months after stent placement does not reduce death or ischemic events, and increases the risk of bleeding complications.