Combination Therapy with Dipyridamole and Clopidogrel for Secondary Stroke Prevention in Aspirin-Intolerant Patients After Myocardial Infarction: Results of a Nationwide Case-Control Study

CNS Drugs. 2019 Feb;33(2):175-185. doi: 10.1007/s40263-018-0591-8.

Abstract

Background and purpose: Combination therapy with dipyridamole and clopidogrel in stroke prevention and long-term outcomes in aspirin-intolerant patients with acute myocardial infarction (AMI) and previous stroke are unknown. This nationwide study analyzed the impact of dipyridamole and clopidogrel on secondary stroke prevention and long-term outcomes in aspirin-intolerant stroke patients after AMI.

Methods: This was a nationwide, case-control study involving 186,112 first AMI patients, 78,607 of whom had a previous history of stroke. In the final analysis, we included 4637 patients taking clopidogrel alone and 208 patients using a combination of clopidogrel and dipyridamole.

Results: The 12-year survival rate was not different between clopidogrel and clopidogrel-dipyridamole groups (log-rank p = 0.6247). Furthermore, there were no differences in event-free survival after stroke (log-rank p = 0.6842), gastrointestinal (GI) bleeding (log-rank p = 0.9539), or intracerebral hemorrhage (ICH; log-rank p = 0.6191) between the two groups. Dipyridamole did not contribute significantly to AMI survival (hazard ratio 0.98, 95% confidence interval 0.84-1.15), and did not show benefits in any of the subgroups regardless of sex, age (younger or older than 75 years), comorbidities, percutaneous coronary intervention, or medications.

Conclusion: No differences were observed in the 12-year survival rate between clopidogrel and clopidogrel-dipyridamole groups. The two groups had balanced event-free survival in recurrent stroke, ICH, GI bleeding, and myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / mortality
  • Clopidogrel / administration & dosage
  • Clopidogrel / adverse effects
  • Clopidogrel / therapeutic use*
  • Dipyridamole / administration & dosage
  • Dipyridamole / adverse effects
  • Dipyridamole / therapeutic use*
  • Disease-Free Survival
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Proportional Hazards Models
  • Secondary Prevention / methods*
  • Stroke / mortality
  • Stroke / prevention & control*
  • Survival Rate

Substances

  • Dipyridamole
  • Clopidogrel