TY - JOUR
T1 - Effect of addition of clopidogrel to aspirin on mortality
T2 - Systematic review of randomized trials
AU - Palacio, Santiago
AU - Hart, Robert G.
AU - Pearce, Lesly A.
AU - Benavente, Oscar R.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/8
Y1 - 2012/8
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.
KW - antiplatelet therapy
KW - clinical trials
KW - clopidogrel
KW - lacunar stroke
KW - mortality
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U2 - 10.1161/STROKEAHA.112.656173
DO - 10.1161/STROKEAHA.112.656173
M3 - Article
C2 - 22826359
AN - SCOPUS:84864189489
VL - 43
SP - 2157
EP - 2162
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 8
ER -