EHJ: Prasugrel outperforms Plavix in reducing CV events, bleeding hard to gauge

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Prasugrel is a more potent antiplatelet agent and reduced both first and subsequent cardiovascular events compared with clopidogrel in patients with acute coronary syndrome, according to the TRITON-TIMI 38 trial published today in the European Heart Journal.

Sabina A. Murphy, MD, from the cardiovascular division at Brigham and Women’s Hospital (BWH) in Boston, and colleagues from the TIMI study group performed a Poisson regression analysis to compare the number of occurrences of the primary endpoint between prasugrel (Eli Lilly and Daiichi Sankyo) and clopidogrel (Plavix from Pfizer) in TRITON-TIMI 38.

The researchers said that they used landmark analytic methods to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event.

The researchers said that patients who took prasugrel for acute coronary syndromes had survived their first cardiovascular event and then suffered a subsequent event, were 35 percent less likely to have a recurrent event (composite endpoint of heart attack, stroke or cardiovascular death) than those who took clopidogrel.

Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4 percent), as was cardiovascular death following the non-fatal event (3.7 vs. 7.1 percent), according to the authors. Overall, there was a reduction of 195 total primary efficacy events with prasugrel compared to clopidogrel (rate ratio 0.79, 95 percent).

The investigators reported that recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). The authors noted that study drug discontinuation was frequent following the initial major bleeding event (42 percent of patients discontinued study drug).

Murphy and colleagues wrote that “if a subject experienced a bleeding event during the trial, the investigator was permitted to discontinue study drug therapy and restart study drug after the bleeding event had subsided. However, a large number of patients in both arms who experienced a major bleeding event permanently discontinued study drug.”

The authors also said that patients who experienced an ischaemic event despite treatment with clopidogrel may be hyporesponders to prasugrel and may require more intensive platelet P2Y12 inhibition to prevent the occurrence of subsequent adverse thrombotic complications.

The researchers also recommended that patients at greatest risk for events, such as those who have already experienced an event while on Plavix, especially diabetic patients, may experience especially favorable effects when treated with a drug, like prasugrel, that provides more intensive inhibition of the platelet P2Y12 receptor.

"Not only do multiple heart events increase healthcare costs due to additional hospitalizations, tests and physician visits, but they also result in higher morbidity for many patients," said Elliott Antman, MD, director of the Samuel A. Levine Cardiac Unit at BWH and principal investigator with the BWH-based TIMI study group for the TRITON-TIMI 38 clinical trial. 

Eli Lilly and Daiichi Sankyo provided the funding for the study.