November 17, 2011

November 10, 2011 (San Francisco, California)— Investigators who explored platelet-function testing for guiding antiplatelet therapy in a low-risk PCI population, who earlier this year had announced that their trial was prematurely halted due to futility, presented what main data they had yesterday here at TCT 2011.

In the Testing Platelet Reactivity in Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy with Prasugrel (TRIGGER-PCI) trial, 423 patients (out of a planned 2150) receiving PCI for stable CAD who had high on-treatment platelet reactivity levels were assigned to therapy with prasugrel (Effient, Lilly/Daiichi-Sanyo) or clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis).

Dr Dietmar Trenk

Randomized patients--only 19% of the 3282 screened--represented those who reached >208 platelet reactivity units (PRU) at VerifyNow P2Y12 (Accumetrics) platelet-function testing while on initial clopidogrel. "High on-clopidogrel platelet reactivity was observed less frequently than expected," acknowledged Dr Dietmar Trenk (Herz-Zentrum Bad Krozingen, Germany) when presenting TRIGGER-PCI at TCT 2011.

As reported by heartwire in March 2011, the trial was stopped after a blinded interim analysis disclosed that there had been only one clinical end point throughout follow-up, a periprocedural MI. That made it all but certain that in the end, there wouldn't be enough end points for meaningful analysis; the trial's primary end point was to be cardiovascular death or MI at six months.

Clinical events were few, probably because the trial's patients were unusually low risk. As Trenk noted, TRIGGER-PCI included patients with stable CAD who had just undergone elective PCI, excluding those with ST-elevation MI, non-ST-elevation MI, or any "known major post-PCI complications."

As anticipated, prasugrel suppressed the high platelet-reactivity levels that are known to persist on clopidogrel, Trenk observed.

Proportion of Patients With High on-Treatment Platelet Reactivity (>208 PRU) After Randomization

Evaluation time Clopidogrel (%) Prasugrel (%) p
Day 90 70.4 5.9 <0.001
Day 176 70.8 5.8 <0.001

PRU=platelet reactivity units by VerifyNow P2Y12 assay (Accumetrics)

But the generally good outcomes in both randomization groups suggest that choosing prasugrel over clopidogrel based on platelet-function testing isn't likely to make much of a clinical difference in such low-risk patients, agreed a panel of experts who spoke to the media about the TRIGGER-PCI trial.

Dr Matthew J Price

Dr Matthew J Price (Scripps Clinic, La Jolla, CA), not a TRIGGER-PCI investigator, noted that "although the hazard associated with on-treatment [platelet] reactivity may be substantial, I think the trial is consistent with [the idea that low] absolute event rates in very-low risk patients means that changing therapy may not provide net clinical benefit."

Patients in TRIGGER-PCI, he observed, were lower risk than in GRAVITAS, which, as heartwire reported in September 2011, confirmed what has been observed for PCI patients in general: that lower platelet-reactivity levels on clopidogrel mean reduced clinical risk.

TRIGGER-PCI investigator Dr Gregg Stone (Columbia University, New York, NY), commented on Price's suggestion that very low-risk patients may not be the best group in which to use platelet function to identify who should most benefit from aggressive antiplatelet therapy. That strategy "works at a population level," Stone said, "but for any individual patient, it's very hard to say what's going to happen based on the platelet-function test."

TRIGGER-PCI was sponsored by Eli Lilly and Daiichi-Sankyo. Trenk discloses receiving consulting fees/honoraria from Eli Lilly, Daiichi-Sankyo, AstraZeneca, and Sanofi-Aventis. Price discloses receiving grant support from Bristol-Myers Squibb and Sanofi-Aventis and receiving consulting fees or honoraria from or serving on a speakers' bureau for Abiomed, AstraZeneca, Boston Scientific, Medtronic, Terumo Medical, Bristol-Myers Squibb, Daiichi-Sankyo/Eli Lilly, Sanofi-Aventis, and WL Gore. Stone reported consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, the Medicines Company, Daiichi-Sankyo, and Eli Lilly.