Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis

Ann Intern Med. 2013 Oct 1;159(7):463-70. doi: 10.7326/0003-4819-159-7-201310010-00006.


Background: Dual-antiplatelet regimens for prevention of recurrent stroke promote antithrombotic effects but may increase the risk for hemorrhage.

Purpose: To qualitatively and quantitatively examine the risk for recurrent stroke and intracranial hemorrhage (ICH) linked to long-term dual- and single-antiplatelet therapy among patients with ischemic stroke and transient ischemic attack.

Data sources: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials through March 2013 without language restrictions.

Study selection: The search identified 7 randomized, controlled trials that involved a total of 39,574 participants and reported recurrent stroke and ICH as outcome measures.

Data extraction: All data from eligible studies were independently abstracted by 2 investigators according to a standard protocol.

Data synthesis: Recurrent stroke risk did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (relative risk [RR], 0.89 [95% CI, 0.78 to 1.01]) or clopidogrel monotherapy (RR, 1.01 [CI, 0.93 to 1.08]). Risk for ICH did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (RR, 0.99 [CI, 0.70 to 1.42]) but was greater among patients receiving dual-antiplatelet therapy than among those receiving clopidogrel monotherapy (RR, 1.46 [CI, 1.17 to 1.82]).

Limitation: Agents used in dual- and single-antiplatelet therapies varied across trials, and the relatively modest number of trials limited subgroup analysis.

Conclusion: Compared with monotherapy, dual-antiplatelet therapy lasting more than 1 year after an index ischemic stroke or transient ischemic attack is not associated with a greater reduction in overall recurrent stroke risk. However, long-term dual-antiplatelet therapy is linked to higher risk for ICH than clopidogrel monotherapy in this patient population.

Primary funding source: Chang Gung Memorial Hospital.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use*
  • Aspirin / adverse effects
  • Aspirin / therapeutic use
  • Brain Ischemia / prevention & control*
  • Clopidogrel
  • Dipyridamole / adverse effects
  • Dipyridamole / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Intracranial Hemorrhages / chemically induced
  • Ischemic Attack, Transient / prevention & control
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Risk Assessment
  • Secondary Prevention
  • Stroke / prevention & control*
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use


  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Dipyridamole
  • Clopidogrel
  • Ticlopidine
  • Aspirin