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September 6, 2011

PRODIGY Questions 2-Year Duration of Dual-Antiplatelet Therapy After Stenting

August 30, 2011—The European Society of Cardiology (ESC) announced that 24-month data from the PRODIGY (Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study) study were presented at its annual meeting in Paris, France.

The ESC noted that PRODIGY is a randomized, multicenter, open-label study evaluating the efficacy and safety of prolonged dual-antiplatelet therapy (DAPT) in patients with coronary disease. The study found that a 24-month duration of DAPT is no better than 6 months of DAPT in preventing adverse cardiac events. The PRODIGY data also showed a consistently greater risk of hemorrhage in the 24-month DAPT group according to all prespecified bleeding definitions, including the recently proposed Bleeding Academic Research Consortium classification. The need for transfusion was also increased in the longer treatment group.

Principal Investigator Marco Valgimigli, MD, concluded that the results “question the validity of current guideline recommendations—which were based on registry data—that at least 12 months' dual-antiplatelet therapy should be pursued after implantation of a drug-eluting stent.” Dr. Valgimigli added, “While we cannot exclude the possibility that a smaller than previously anticipated benefit may still exist in prolonging therapy with clopidogrel for several months after coronary stenting, our study clearly shows that the benefit-to-risk ratio of prolonged therapy has been overemphasized.”

According to the ESC, the PRODIGY study was a 4 X 2 randomized, three-center, open-label clinical trial designed to assess the efficacy and safety of prolonged clopidogrel therapy for up to 24 months in all-comer patients receiving a balanced combination of drug-eluting stents (with various anti-intimal hyperplasia potency and being both first- and second-generation devices). Patients were 18 years of age or older with chronic stable coronary artery disease or acute coronary syndromes, including non–ST-elevation and ST-elevation myocardial infarction.

More than 2,000 patients who were scheduled for elective, urgent, or emergency coronary angioplasty were randomly assigned in a 1:1:1:1 fashion to one of four stent types: an everolimus-eluting stent, paclitaxel-eluting stent, zotarolimus-eluting stent, or third-generation thin-strut bare-metal stent. Dr. Valgimigli stated that randomization to the four different types was justified by the different safety profile of each type of device, which was meant to ensure that patients in the two main study groups (6-month DAPT and 24-month DAPT) received exactly the same stent types. At 30 days, patients in each stent group were then further randomized to either 6 or 24 months of DAPT.

The primary objective of the study was to assess whether 24-month DAPT, consisting of clopidogrel and aspirin after coronary stenting, was associated with a lower cumulative incidence of all-cause mortality, nonfatal myocardial infarction, or cerebrovascular accident (the primary outcome) than 6-month DAPT.

The results showed that the cumulative risk of the primary outcome at 2 years was 10.1% with the 24-month treatment and 10% with the 6-month treatment (hazard ratio, 0.98; 95% confidence interval, 0.74–1.29; P = .91). The individual risks of death, myocardial infarction, cerebrovascular accident, or stent thrombosis did not differ between the two groups. Among the patients receiving long-term DAPT, there was an approximately two-fold greater risk of type 5, 3, or 2 bleeding events (hazard ratio, 2.17; 95% confidence interval, 1.02–3.13; P= .037) according to the Bleeding Academic Research Consortium classification. The risks of TIMI-defined major bleeding and red blood cell transfusion were also increased in the 24-month treatment group.

Regarding the implications of the results, Dr. Valgimigli commented, “While a formal economic analysis will follow, the results of this study have important implications for heath care expenditure—for this study shows that prolonging therapy with clopidogrel beyond 6 months is not only associated with no clinical benefit but also with a significant increase in actionable bleeding events requiring rehospitalizations and multiple diagnostic and therapeutic resources.”

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