Elderly patients with acute coronary syndromes managed without revascularization: Insights into the safety of long-term dual antiplatelet therapy with reduced-dose prasugrel versus standard-dose clopidogrel

Matthew T. Roe, Shaun G. Goodman, E. Magnus Ohman, Susanna R. Stevens, Judith S. Hochman, Shmuel Gottlieb, Felipe Martinez, Anthony J. Dalby, William E. Boden, Harvey D. White, Dorairaj Prabhakaran, Kenneth J. Winters, Philip E. Aylward, Jean Pierre Bassand, Darren K McGuire, Diego Ardissino, Keith A A Fox, Paul W. Armstrong

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

BACKGROUND - : Dual antiplatelet therapy in older versus younger patients with acute coronary syndromes is understudied. Low-dose prasugrel (5 mg/d) is recommended for younger, lower-body-weight patients and elderly patients with acute coronary syndromes to mitigate the bleeding risk of standard-dose prasugrel (10 mg/d). METHODS AND RESULTS - : A total of 9326 medically managed patients with acute coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial (<75 years of age, n=7243; ≥75 years of age, n=2083) were randomized to prasugrel (10 mg/d; 5 mg/d for those ≥75 or <75 years of age and <60 kg in weight) or clopidogrel (75 mg/d) plus aspirin for ≤30 months. A total of 515 participants ≥75 years of age (25% of total elderly population) had serial platelet reactivity unit measurements in a platelet-function substudy. Cumulative risks of the primary end point (cardiovascular death/myocardial infarction/stroke) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding increased progressively with age and were ≥2-fold higher in older participants. Among those ≥75 years of age, TIMI major bleeding (4.1% versus 3.4%; hazard ratio, 1.09; 95% confidence interval, 0.57-2.08) and the primary end point rates were similar with reduced-dose prasugrel and clopidogrel. Despite a correlation between lower 30-day on-treatment platelet reactivity unit values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for platelet reactivity unit values among participants ≥75 years of age in the platelet-function substudy (P=0.06). No differences in weight were seen in all participants ≥75 years of age with versus without TIMI major/minor bleeding in both treatment groups. CONCLUSIONS - : Older age is associated with substantially increased long-term cardiovascular risk and bleeding among patients with medically managed acute coronary syndromes, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared with clopidogrel in elderly patients. No significant interactions among weight, pharmacodynamic response, and bleeding risk were observed between reduced-dose prasugrel and clopidogrel in elderly patients.

Original languageEnglish (US)
Pages (from-to)823-833
Number of pages11
JournalCirculation
Volume128
Issue number8
DOIs
StatePublished - Aug 20 2013

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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