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
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.
- Received February 27, 2013.
- Revision received June 12, 2013.
- Accepted June 28, 2013.