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.

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.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov/ct2/home. Unique identifier: NCT0069999.

• Authors: 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
• Journal: Circulation (Circulation) Vol. 128 Issue 8 Pg. 823-33 (Aug 20 2013) ISSN: 1524-4539 [Electronic] United States
• PMID: 23852610 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• Thiophenes
• Clopidogrel
• Prasugrel Hydrochloride
• Ticlopidine
• Aspirin

Topics

• Acute Coronary Syndrome (drug therapy)
• Age Factors
• Aged
• Aged, 80 and over
• Aspirin (adverse effects, therapeutic use)
• Clopidogrel
• Disease Management
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Hemorrhage (epidemiology, prevention & control)
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Percutaneous Coronary Intervention
• Piperazines (adverse effects, therapeutic use)
• Platelet Aggregation Inhibitors (adverse effects, therapeutic use)
• Prasugrel Hydrochloride
• Purinergic P2Y Receptor Antagonists (adverse effects, therapeutic use)
• Risk Factors
• Thiophenes (adverse effects, therapeutic use)
• Ticlopidine (adverse effects, analogs & derivatives, therapeutic use)
• Treatment Outcome