Sponsors Pull the Plug on TRIGGER-PCI

Dealing another potential blow to the emerging field of personalized antiplatelet therapy, the TRIGGER-PCI trial—comparing the drugs clopidogrel and prasugrel in poor-clopidogrel-responders—was stopped early after an interim analysis revealed a primary event rate too low to allow for any meaningful comparison between the 2 agents. The news came on March, 18, 2011, via a joint announcement by the study’s sponsors.

TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel), sponsored by Eli Lilly (Indianapolis, IN) and Daiichi-Sankyo (Parsippany, NJ), was designed to enroll 2,150 patients with stable angina who received DES during a successful, uncomplicated PCI procedure. Patients were then randomized on the basis of poor clopidogrel response, defined as P2Y12 reactivity units greater than 208 on the VerifyNow assay (Accumetrics, San Diego, CA), to continue receiving clopidogrel (75 mg daily) or switch to prasugrel (60 mg loading dose, 10 mg daily). The primary endpoint was CV death and MI at 6 months.

The trial was scheduled to last until July 2012, but after a blinded interim analysis in over 400 patients revealed a much lower than expected primary event rate, the study was halted. “The event rate is extremely low, significantly lower than in GRAVITAS, and as a result, it is highly unlikely that the trial ever will be able to enroll enough patients to support a comparison between prasugrel and clopidogrel in this patient population,” Gregg W. Stone, MD, of Columbia University Medical Center and the lead investigator in the United States for TRIGGER-PCI, told TCTMD in a telephone interview.

First GRAVITAS, Now TRIGGER-PCI

GRAVITAS (Gauging Responsiveness with A VerifyNow assay - Impact on Thrombosis And Safety), which was just published this week in the Journal of the American Medical Association, failed to support using high-dose clopidogrel therapy to curb high on-treatment platelet reactivity in a mixed patient population with stable and unstable angina (Price MJ, et al. JAMA.2011;305:1097-1105). In GRAVITAS, the primary endpoint rate was 2.3%, while in TRIGGER-PCI, the rate was also under 3%, according to Jeff Riesmeyer, MD, of Eli Lilly.

Dr. Riesmeyer stressed that the trial was not stopped for any safety or efficacy reasons, and that Eli Lilly intends to continue investigations of prasugrel in patients with ACS, the indication for which the drug has been approved. He added that the decision to halt TRIGGER-PCI should not impact the care of any ACS patients currently taking prasugrel.

Still, GRAVITAS and now TRIGGER-PCI do cast doubt on the validity of using platelet function assay results to guide antiplatelet therapy, at least in stable angina patients, Dr. Stone commented.

“I think for stable CAD, this settles the question,” he said. “In this population, on the basis of both GRAVITAS and TRIGGER-PCI, a personalized approach to platelet function analysis does not appear to be necessary.”

And in terms of stable coronary disease patients who have successful, uncomplicated DES procedures, “this raises the question as to how much benefit they’re getting from clopidogrel at all,” Dr. Stone said.

Note: Dr. Stone is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Source:

Daiichi Sankyo, Inc. and Eli Lilly and Company. Discontinuation of TRIGGER-PCI Study Media Statement [press release]. March 18, 2010.

Related Stories:

• GRAVITAS Published: No Benefit from High-Dose Clopidogrel in Poor Responders
• Some Clopidogrel Poor Responders Helped by Higher Dosing
• Double-Dose Clopidogrel Lowers CV Events in ACS Patients Undergoing PCI