Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

N Engl J Med. 2008 Sep 18;359(12):1238-51. doi: 10.1056/NEJMoa0805002. Epub 2008 Aug 27.

Abstract

Background: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel.

Methods: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.

Results: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).

Conclusions: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Benzimidazoles / therapeutic use
  • Benzoates / therapeutic use
  • Brain Ischemia / epidemiology
  • Brain Ischemia / prevention & control
  • Clopidogrel
  • Delayed-Action Preparations
  • Dipyridamole / adverse effects
  • Dipyridamole / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Factor Analysis, Statistical
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Proportional Hazards Models
  • Risk
  • Secondary Prevention
  • Stroke / drug therapy*
  • Stroke / epidemiology
  • Stroke / prevention & control
  • Telmisartan
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Vascular Diseases / mortality

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Benzoates
  • Delayed-Action Preparations
  • Platelet Aggregation Inhibitors
  • Dipyridamole
  • Clopidogrel
  • Ticlopidine
  • Aspirin
  • Telmisartan

Associated data

  • ClinicalTrials.gov/NCT00153062