TRIGGER-PCI Trial of Prasugrel After PCI Ended Early Due to Lack of Events

November 9, 2011—The Cardiovascular Research Foundation (CRF) announced that results of the TRIGGER-PCI (Testing Platelet Reactivity in Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) clinical trial were presented today at CRF's annual Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco. Eli Lilly and Company (Indianapolis, IN) and Daiichi Sankyo Company, Ltd. (Tokyo, Japan), the makers of prasugrel, sponsored the trial.

According to CRF, TRIGGER-PCI compared prasugrel to clopidogrel for use in patients with high on-clopidogrel platelet reactivity (HCPR) after percutaneous coronary intervention (PCI). The trial was ended early due to relatively few occurrences of cardiac death or myocardial infarction—the primary endpoint—at 6-month follow-up.

CRF noted that the risk of ischemic events after PCI is elevated in patients with HCPR. Novel P2Y12 receptor antagonists, such as prasugrel, are more potent than clopidogrel and may thus improve outcomes with respect to ischemic events but may also increase the bleeding risk.

As detailed by CRF, the trial was a multicenter, double-blind, randomized controlled trial. Platelet reactivity was assessed 2 to 7 hours after the first maintenance dose of 75 mg of clopidogrel or 10 mg of prasugrel the day after PCI was performed, which followed a one-time 60-mg loading dose of prasugrel for patients in that arm of the trial. 

TRIGGER-PCI aimed to randomize 2,150 patients to have a 93% power for detecting a 50% relative risk reduction with prasugrel in terms of the primary endpoint (cardiovascular death or myocardial infarction within 6 months). The study was prematurely terminated due to futility on March 18, 2011, at which time, 236 patients completed 6 months follow-up. Only one clinical endpoint, a periprocedural myocardial infarction, was observed.

“HCPR (> 208 P2Y12 reaction units by VerifyNow P2Y12 test [Accumetrics, Inc., San Diego, CA]) was observed less frequently than expected,” said Professor Dietmar Trenk, PhD. Professor Trenk noted that the trial demonstrated that compared with the 75-mg standard dose of clopidogrel, 10 mg of prasugrel substantially decreased platelet reactivity in patients with HCPR after elective PCI. “Given the low event rate in elective PCI patients without periprocedural complications, it was not possible to assess the risk/benefit ratio with prasugrel treatment. Therefore, the study was terminated prematurely for futility,” concluded Professor Trenk.