Abstract
Background There is no clear consensus on whether aspirin offers better outcomes in terms of
secondary cardiovascular disease prevention compared with clopidogrel.
Objective The aim of the study was to compare the safety and efficacy of clopidogrel versus
aspirin in patients with established cardiovascular disease.
Methods A systematic review of MEDLINE (via PubMed), Scopus, and Cochrane Library databases
(last search date: August 28, 2021) was performed according to the PRISMA (Preferred
Reporting Items for Systematic Reviews and Meta-analyses) statement for randomized
control trials (RCTs) of clopidogrel versus aspirin as monotherapy in patients with
established cardiovascular disease. Random-effects meta-analyses were performed.
Results Five RCTs incorporating 26,855 patients (clopidogrel: 13,426; aspirin: 13,429) were
included. No statistically significant difference was observed between clopidogrel
and aspirin in terms of all-cause mortality (odds ratio [OR]: 1.01 [95% confidence
interval, CI: 0.91–1.13]; p = 0.83), ischemic stroke (OR: 0.87 [95% CI: 0.71–1.06]; p = 0.16), and major bleeding rates (OR: 0.77 [95% CI: 0.56–1.06]; p = 0.11). Patients receiving clopidogrel had borderline lower risk for major adverse
cardiovascular events (MACE) (OR: 0.84 [95% CI: 0.71–1.00]; p = 0.05) and lower risk for nonfatal myocardial infarction (OR: 0.83 [95% CI: 0.71–0.97];
p = 0.02, relative risk reduction = 16.9%, absolute risk reduction = 0.5%, number needed
to treat = 217 for a mean period of 20 months) compared with patients receiving aspirin.
Conclusion In patients with established cardiovascular disease, clopidogrel was associated with
a 17% relative-risk reduction for nonfatal MI, borderline decreased risk for MACE,
and similar risk for all-cause mortality, stroke, and major bleeding compared with
aspirin.
Protocol Registration PROSPERO CRD42021283866.
Keywords
clopidogrel - aspirin - monotherapy - cardiovascular disease - efficacy - myocardial
infarction - stroke - mortality - safety - major bleeding
