CREDO In this industry-sponsored trial, researchers assessed the benefit of combination antiplatelet therapy (aspirin plus clopidogrel) both before and after elective percutaneous coronary intervention (PCI). They randomized 2116 patients to a 300-mg loading dose of clopidogrel or placebo (3 to 24 hours before PCI); both groups received aspirin (325 mg). After PCI, both groups received clopidogrel (75 mg/day) and aspirin (325 mg/day) for 28 days. From 28 days to 1 year, the clopidogrel group received 75 mg/day of clopidogrel, and the placebo group received placebo; both groups continued to receive standard therapy, including aspirin. The 1-year study was completed by 63% of the clopidogrel group and 61% of the placebo group. Clopidogrel did not show a significant benefit over placebo in the 28-day composite endpoint of death, MI, or urgent target-vessel revascularization, although there was some benefit in patients treated with clopidogrel at least 6 hours before PCI. Compared with the placebo group, the clopidogrel group had a 26.9% relative reduction in risk for the 1-year composite endpoint of death, MI, or stroke (raw rates, 11.5% and 8.5%). Clopidogrel recipients fared better than placebo recipients at 1 year regardless of sex, diabetes status, acute coronary syndrome status, GPIIb/IIIa use, and stent use, but the benefit reached statistical significance only in stented patients and in nondiabetic patients. Major bleeding was more common with long-term clopidogrel than placebo (8.8% vs. 6.7%, P=0.07). Comment: These results add to evidence showing that long-term therapy with clopidogrel and aspirin significantly reduces risk for adverse ischemic events after elective PCI but modestly increases bleeding risk. The benefit of a preprocedure clopidogrel loading dose is not clear from these data. Steinhubl SR et al. for the CREDO Investigators. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: A randomized controlled trial. JAMA 2002 Nov 20; 288:2411-20.