Elderly Patients with Acute Coronary Syndromes Managed Without Revascularization Insights into the Safety of Long-Term Dual Antiplatelet Therapy with Reduced-Dose Prasugrel vs. Standard-Dose Clopidogrel.
Circulation. 2013 Jul 12;
Authors: Roe MT, Goodman SG, Ohman EM, Stevens SR, Hochman JS, Gottlieb S, Martinez F, Dalby AJ, Boden WE, White HD, Prabhakaran D, Winters KJ, Aylward PE, Bassand JP, McGuire DK, Ardissino D, Fox KA, Armstrong PW
BACKGROUND: Dual antiplatelet therapy in older vs. younger patients with acute coronary syndromes (ACS) is under-studied. Low-dose prasugrel (5mg/d) is recommended for younger, lower-body-weight ACS patients and elderly ACS patients to mitigate bleeding risk of standard-dose prasugrel (10mg/d).
METHODS AND RESULTS: 9326 medically managed ACS patients from the TRILOGY trial (7243 <75y; 2083 ≥75y) were randomized to prasugrel (10mg/d; 5mg/d for those ≥75y or <75y and <60kg) or clopidogrel (75mg/d), plus aspirin, for ≤30 months. A total of 515 participants ≥75y (25% of total elderly population) had serial platelet reactivity unit (PRU) measurements in a platelet-function substudy (PFS). Cumulative risks of the primary endpoint (cardiovascular death/myocardial infarction/stroke) and TIMI major bleeding increased progressively with age and were ≥twofold higher in older participants. Among those ≥75y, TIMI-major bleeding (4.1% vs. 3.4%, HR=1.09, 95%CI: 0.57-2.08) and primary endpoint rates were similar with reduced-dose prasugrel vs. clopidogrel. Despite a correlation between lower 30-day on-treatment PRU values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for PRU values among participants ≥75y in the PFS (P=0.06). No differences in weight were seen in all participants ≥75y with vs. without TIMI-major/minor bleeding in both treatment groups.
CONCLUSIONS: Older age is associated with substantially increased long-term cardiovascular risk and bleeding among medically managed ACS patients, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel vs. clopidogrel in elderly patients. No significant interaction among weight, pharmacodynamic response, and bleeding risk was observed between reduced-dose prasugrel vs. clopidogrel in elderly patients.
CLINICAL TRIAL REGISTRATION INFORMATION: http://clinicaltrials.gov/ct2/home. Identifier: NCT0069999.
PMID: 23852610 [PubMed - as supplied by publisher]