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

Study Questions:

What is the efficacy and safety of reduced-dose prasugrel compared with clopidogrel in the elderly population?

Methods:

A total of 9,326 medically managed patients with acute coronary syndrome (ACS) from the TRILOGY ACS trial (7,243 <75 years; 2,083 ≥75 years) were randomized to prasugrel (10 mg/d; 5 mg/d for those ≥75 years or <75 years and <60 kg) or clopidogrel (75 mg/d), plus aspirin, for ≤30 months. A total of 515 participants ≥75 years (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 [MI]/stroke) and Thrombolysis in MI (TIMI) major bleeding were assessed. Kaplan-Meier event curves were plotted for the primary efficacy composite and noncoronary artery bypass grafting (CABG)-related TIMI major bleeding endpoint rates during the 30 months of follow-up.

Results:

Cumulative risks of the primary endpoint (cardiovascular death/MI/stroke) and TIMI major bleeding increased progressively with age and were ≥ twofold higher in older participants. Among those ≥75 years, TIMI major bleeding (4.1% vs. 3.4%; hazard ratio, 1.09; 95% confidence interval, 0.57-2.08) and primary endpoint rates were similar with reduced-dose prasugrel versus 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 ≥75 years in the PFS (p = 0.06). No differences in weight were seen in all participants ≥75 years with versus without TIMI major/minor bleeding in both treatment groups.

Conclusions:

The authors concluded that older age is associated with substantially increased long-term cardiovascular risk and bleeding among medically managed ACS patients, with no differences in outcomes with reduced-dose prasugrel versus clopidogrel in elderly patients.

Perspective:

This exploratory subgroup analysis of elderly patients from the TRILOGY ACS trial reported steeply increased risks of ischemic and bleeding events with increasing age among ACS patients managed without revascularization, and no difference in the risks of both ischemic and bleeding outcomes with reduced-dose prasugrel versus clopidogrel. Large-scale, prospective clinical outcomes trials of antithrombotic therapies with an adequate number of elderly ACS patients are indicated in order to clearly delineate optimal and safe treatment strategies for this vulnerable population. Such studies should also consider incorporating age-specific dosing regimens.

Clinical Topics: Acute Coronary Syndromes

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Follow-Up Studies, Thiophenes, Cardiovascular Diseases, Risk Factors, Ticlopidine, Piperazines, Blood Platelets, Confidence Intervals


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