Prasugrel 5 mg, Clopidogrel Similarly Safe, Effective in Non-PCI Elderly With ACS

July 30, 2013

DALLAS, TX — Long-term ischemic and bleeding risks climb with advancing age in elderly patients medically managed for acute coronary syndromes (ACS), as might be expected, but adding low-dose (5-mg/day) prasugrel (Effient, Lilly/Daiichi-Sanyo) to aspirin instead of standardclopidogrel 75 mg/day doesn't improve their clinical or safety outcomes, suggests an exploratory analysis based on the TRILOGY ACS trial [1]. The two thienopyridine antiplatelet agents were similarly safe and effective in the elderly patients regardless of their weight.

Still, that's a better performance than full-dose prasugrel gave in the primary analysis of the trial's younger patient group. In the randomized TRILOGY ACS[2], 7243 patients <75 years of age with ACS but no planned PCI showed safety and clinical outcomes over a mean follow-up of 17 months that were similar with either prasugrel 10 mg/day or standard clopidogrel, Dr Matthew Roe (Duke Clinical Research Institute, Durham, NC), lead author of both the current and primary analyses, reminded heartwire . Nor were there noteworthy differences when the patients <75 years were combined with 2083 patients >75 years similarly managed with either prasugrel 5 mg/day or standard clopidogrel.

Roe said the trial's low prasugrel dosage for the elderly stemmed from concerns in the previous TRITON-TIMI 38 trial of high-risk ACS patients slated for PCI, in which 10-mg/day prasugrel significantly improved clinical outcomes compared with clopidogrel but led to a significant excess of major and life-threatening bleeding. So TRILOGY ACS investigators cut the dosage in half for their patients >75 years and anyone weighing <60 kg, considered more vulnerable to drug-related bleeding complications.

As a result, Roe said, in the elderly TRILOGY ACS patients, "we mitigated the bleeding risk but have no efficacy signal." He acknowledged, however, that the current exploratory analysis focusing solely on the older patients wasn't statistically powered for efficacy and so is only hypothesis-generating.

Hazard Ratios (95% CI) for Efficacy and Safety Outcomes Through 30 Months by Age (Over All Patients) and by Antiplatelet (Among Patients >75) in TRILOGY ACS Post hoc Analysis

End points Age >75 vs <75, n=9326 Prasugrel vs clopidogrel, n=2083
CV death/MI/stroke* 2.65 (2.37–2.97) 1.03 (0.86–1.22)
All-cause mortality 3.27 (2.85–3.76) 0.93 (0.76–1.14)
Severe bleeding (GUSTO criteria) 3.33 (1.89–5.85) 0.72 (0.31–1.68)
Major bleeding (TIMI criteria) 2.15 (1.44–3.20) 1.09 (0.57–2.08)
Major/minor bleeding (TIMI criteria) 2.00 (1.46–2.75) 0.90 (0.53–1.50)

*Primary end point

TRILOGY ACS--in the primary and this exploratory analysis--still makes no case for preferring prasugrel over the off-patent clopidogrel in patients, elderly or not, with medically managed ACS. Roe said, however, that in an ongoing secondary analysis of the trial, "we found a couple subgroups that tended to show some benefit. Patients who were smokers at baseline did look like they benefited [more] from prasugrel."

That may turn out to be true, he said, and he and his colleagues are currently working to write up the analysis. "But it's hard to propose a group [in TRILOGY ACS] that should have preference for prasugrel when the overall trial was neutral."

TRILOGY ACS was funded by Eli Lilly and Daiichi Sankyo. Roe discloses receiving grant support from Lilly, Bristol-Myers Squibb, Hoffmann-La Roche, Novartis, Schering-Plough, and KAI Pharmaceuticals; consulting fees from Lilly, Daiichi Sankyo, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Janssen Pharmaceuticals, KAI Pharmaceuticals, Sanofi, Helsinn Therapeutics, Novartis, AstraZeneca, and Orexigen; and lecture fees from AstraZeneca and Janssen. Disclosures for the coauthors are listed in the paper.


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