Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis

Stroke. 2014 Feb;45(2):492-503. doi: 10.1161/STROKEAHA.113.002590. Epub 2013 Dec 24.

Abstract

Background and purpose: The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis.

Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science. Twenty-two studies comprising 173 371 patients were included.

Results: In the overall population, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in comparison to aspirin monotherapy reduced the relative risk of total stroke by 20% (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.73-0.88; P<0.0001; I(2)=28%) and of ischemic stroke or transient ischemic attack by 23% (RR, 0.77; 95% CI, 0.69-0.85; P<0.0001; I(2)=18%) without increasing the risk of intracranial hemorrhage. In the secondary prevention cohort, DAPT with aspirin and clopidogrel also reduced the relative risk of total stroke by 24% as compared with aspirin alone (RR, 0.76; 95% CI, 0.68-0.86; P<0.0001; I(2)=0%). DAPT with prasugrel or ticagrelor and aspirin versus DAPT with clopidogrel and aspirin was not associated with a risk reduction of stroke.

Conclusions: DAPT with clopidogrel and aspirin compared with aspirin effectively reduces the risk of total and ischemic stroke in the overall cohort consisting of patients with cardiovascular disease without increase in intracranial hemorrhage, as well as decreases the risk of a recurrent total stroke in patients with a previous stroke/transient ischemic attack. Our meta-analysis suggests that DAPT including low-dose aspirin (75-100 mg) and clopidogrel (75 mg) should be further investigated as a strategy to reduce recurrent strokes.

Clinical trial registration url: http://www.crd.york.ac.uk/prospero. Unique identifier: CRD42011001596.

Keywords: antiplatelet agents; intracranial hemorrhages; stroke.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / therapeutic use
  • Aged
  • Aspirin / therapeutic use
  • Cerebral Hemorrhage / epidemiology
  • Cerebrovascular Disorders / prevention & control*
  • Clopidogrel
  • Cohort Studies
  • Data Interpretation, Statistical
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ischemic Attack, Transient / prevention & control
  • Male
  • Middle Aged
  • Piperazines / therapeutic use
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Population
  • Prasugrel Hydrochloride
  • Randomized Controlled Trials as Topic
  • Receptors, Purinergic P2 / drug effects
  • Secondary Prevention
  • Stroke / prevention & control
  • Thiophenes / therapeutic use
  • Ticagrelor
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Vascular Diseases / complications*
  • Vascular Diseases / drug therapy*

Substances

  • Piperazines
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2
  • Thiophenes
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine
  • Ticlopidine
  • Aspirin