Effect of addition of clopidogrel to aspirin on mortality: Systematic review of randomized trials

Santiago Palacio, Robert G. Hart, Lesly A. Pearce, Oscar R. Benavente

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE-: In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials. METHODS-: Randomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≫14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported. RESULTS-: Twelve trials included 90 934 participants (mean age, 63 years; 70% men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days-3 months; OR, 0.93; 95% CI, 0.87-0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95% CI, 0.91-1.04) trials after 1 long-term trial (the SPS3 trial) was excluded because of heterogeneity. Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1.35; 95% CI, 0.97-1.90) and a reduction in myocardial infarction (OR, 0.82; 95% CI, 0.74-0.91). CONCLUSIONS-: The addition of clopidogrel to aspirin has no overall effect on mortality. The SPS3 trial results are outliers, possibly because of a lower prevalence of coronary artery ischemia. Addition of clopidogrel to aspirin increases fatal bleeding and reduces myocardial infarction. CLINICAL TRIAL REGISTRATION-: URL: http//www.clinicaltrials.gov. Unique identifier: NCT00059306.

Original languageEnglish (US)
Pages (from-to)2157-2162
Number of pages6
JournalStroke
Volume43
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

clopidogrel
Aspirin
Mortality
Myocardial Infarction
Hemorrhage
Lacunar Stroke
Secondary Prevention
Vascular Diseases
Meta-Analysis
Coronary Vessels

Keywords

  • antiplatelet therapy
  • clinical trials
  • clopidogrel
  • lacunar stroke
  • mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Effect of addition of clopidogrel to aspirin on mortality : Systematic review of randomized trials. / Palacio, Santiago; Hart, Robert G.; Pearce, Lesly A.; Benavente, Oscar R.

In: Stroke, Vol. 43, No. 8, 08.2012, p. 2157-2162.

Research output: Contribution to journalArticle

Palacio, Santiago ; Hart, Robert G. ; Pearce, Lesly A. ; Benavente, Oscar R. / Effect of addition of clopidogrel to aspirin on mortality : Systematic review of randomized trials. In: Stroke. 2012 ; Vol. 43, No. 8. pp. 2157-2162.
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abstract = "BACKGROUND AND PURPOSE-: In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials. METHODS-: Randomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≫14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported. RESULTS-: Twelve trials included 90 934 participants (mean age, 63 years; 70{\%} men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days-3 months; OR, 0.93; 95{\%} CI, 0.87-0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95{\%} CI, 0.91-1.04) trials after 1 long-term trial (the SPS3 trial) was excluded because of heterogeneity. Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1.35; 95{\%} CI, 0.97-1.90) and a reduction in myocardial infarction (OR, 0.82; 95{\%} CI, 0.74-0.91). CONCLUSIONS-: The addition of clopidogrel to aspirin has no overall effect on mortality. The SPS3 trial results are outliers, possibly because of a lower prevalence of coronary artery ischemia. Addition of clopidogrel to aspirin increases fatal bleeding and reduces myocardial infarction. CLINICAL TRIAL REGISTRATION-: URL: http//www.clinicaltrials.gov. Unique identifier: NCT00059306.",
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N2 - BACKGROUND AND PURPOSE-: In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials. METHODS-: Randomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≫14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported. RESULTS-: Twelve trials included 90 934 participants (mean age, 63 years; 70% men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days-3 months; OR, 0.93; 95% CI, 0.87-0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95% CI, 0.91-1.04) trials after 1 long-term trial (the SPS3 trial) was excluded because of heterogeneity. Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1.35; 95% CI, 0.97-1.90) and a reduction in myocardial infarction (OR, 0.82; 95% CI, 0.74-0.91). CONCLUSIONS-: The addition of clopidogrel to aspirin has no overall effect on mortality. The SPS3 trial results are outliers, possibly because of a lower prevalence of coronary artery ischemia. Addition of clopidogrel to aspirin increases fatal bleeding and reduces myocardial infarction. CLINICAL TRIAL REGISTRATION-: URL: http//www.clinicaltrials.gov. Unique identifier: NCT00059306.

AB - BACKGROUND AND PURPOSE-: In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials. METHODS-: Randomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≫14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported. RESULTS-: Twelve trials included 90 934 participants (mean age, 63 years; 70% men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days-3 months; OR, 0.93; 95% CI, 0.87-0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95% CI, 0.91-1.04) trials after 1 long-term trial (the SPS3 trial) was excluded because of heterogeneity. Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1.35; 95% CI, 0.97-1.90) and a reduction in myocardial infarction (OR, 0.82; 95% CI, 0.74-0.91). CONCLUSIONS-: The addition of clopidogrel to aspirin has no overall effect on mortality. The SPS3 trial results are outliers, possibly because of a lower prevalence of coronary artery ischemia. Addition of clopidogrel to aspirin increases fatal bleeding and reduces myocardial infarction. CLINICAL TRIAL REGISTRATION-: URL: http//www.clinicaltrials.gov. Unique identifier: NCT00059306.

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