The long-term use of prasugrel did not reduce adverse cardiovascular outcomes in patients with non-ST-elevation acute coronary syndromes selected for medical management without revascularization, compared with clopidogrel, in a new study published on Aug. 26 in The New England Journal of Medicine and presented on Sunday as part of the ESC Congress 2012 in Munich.

The study, called TRILOGY ACS, randomized 9,326 patients. In the primary analysis of 7,243 patients  < 75 years of age, the primary outcome of cardiovascular death, myocardial infarction, or stroke occurred in 13.9 percent of the prasugrel group versus 16.0 percent of the clopidogrel group (hazard ratio [HR] 0.91, p = 0.21) at 30 months. Similar results were seen in the overall population, including those ≥ 75 years of age. At 30 months among all patients, cardiovascular death, myocardial infarction, or stroke occurred in 18.7 percent of the prasugrel group versus 20.3 percent of the clopidogrel group (p=NS).

 

Other findings indicated that rates of severe and intracranial bleeding were similar in both the prasugrel and clopidogrel groups. "Given that this patient population has a high risk for bleeding, the fact that there weren’t any differences between the two groups in major bleeding and intracranial bleeding, even when elderly patients treated with a lower dose of prasugrel were included in the analysis, is very reassuring for the clinical use of this drug where it currently has an approved indication for use (i.e., ACS patients undergoing PCI)," said Dominick J. Angiolillo, MD, PhD, FACC, associate professor of medicine and director of Cardiovascular Research and the Center for Thrombosis Research at the University of Florida, College of Medicine in Jacksonville. However, major or minor bleeding was observed to increase with prasugrel – a result that differs from the clear benefit of prasugrel over clopidogrel in reducing cardiovascular events in patients with planned PCI that was seen in the TRITON-TIMI 38 trial.

Additional Resources Clinical Trial Summary  Download the Presentation Slides  UA/NSTEMI Practice Guideline TRITON-TIMI 38 Clinical Trial Summary

Study authors did note signs of intensified platelet inhibition in the prasugrel group, suggesting a need for "further study of differences in the response to intensified platelet inhibition for patients receiving medical therapy without revascularization, as compared with those undergoing revascularization, for treatment of an index cardiac event." In addition, Angiolillo suggests that while the trial did not reach its primary endpoint, it is a unique and very informative trial that provides important insights for potential future trial development. "Since the patient population is high-risk as supported by the high event rates, and a separation of the event curves was observed after the 12 months, this may suggest that we may need trials of longer duration," he said. "In addition, future trials may want to place more emphasis on the multiple recurrent events occurring over the duration of the trial, rather than the just when the first primary event occurs, as this may be more role reflective of the role of a given strategy for secondary prevention of ischemic recurrences and also reflect how we follow our patients in real world clinical practice."

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