Key result
Clopidogrel significantly decreased the risk of major adverse cardiovascular events (HR 0.78) compared with aspirin in patients with symptomatic peripheral artery disease, without increasing bleeding risk.
Why the study?
Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease, but the advent of new antithrombotic strategies prompted an updated analysis of available evidence.
Does antiplatelet therapy (monotherapy or dual therapy) reduce major adverse cardiovascular events and limb complications compared to aspirin or placebo in adult patients with symptomatic peripheral artery disease?
Meta-Analysis (n=51,465)
Does antiplatelet therapy (monotherapy or dual therapy) reduce major adverse cardiovascular events and limb complications compared to aspirin or placebo in adult patients with symptomatic peripheral artery disease?
Effect estimate: HR 0.78 (95% CI 0.65-0.93)
In symptomatic PAD, clopidogrel and ticagrelor monotherapy significantly reduce major adverse cardiovascular events compared to aspirin without increasing bleeding risk, whereas dual antiplatelet therapy increases bleeding without significant cardiovascular benefit.
May support clopidogrel preference over aspirin in symptomatic PAD; extends low-certainty mixed evidence but leaves open need for dedicated RCTs.
BACKGROUND: Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD. METHODS: We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses. RESULTS: We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65-0.93) and ticagrelor (HR 0.80; 95% CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95% CrI 0.43-1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed a significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk. CONCLUSION: This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.
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Carlo et al. (2020) conducted a meta-analysis in Symptomatic Peripheral Artery Disease (PAD) (n=51,465). Clopidogrel vs. Aspirin was evaluated on Major adverse cardiovascular events (composite of CV mortality, myocardial infarction, and stroke) (HR 0.78, 95% CI 0.65-0.93). Clopidogrel significantly decreased the risk of major adverse cardiovascular events (HR 0.78) compared with aspirin in patients with symptomatic peripheral artery disease, without increasing bleeding risk.
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