Efficacy and Safety of Antiplatelet Therapies in Symptomatic Peripheral Artery Disease: A Systematic Review and Network Meta-Analysis

Abstract

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 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.

Plasma Pentraxin-3 as a Predictor for Peripheral Arterial Disease in Maintenance Hemodialysis Egyptian Patients: A Single-Center Study

“…PTX3 is a more comprehensive inflammatory biomarker than traditional biomarkers, and it has links to renal fibrosis, cardiovascular disease, malnutrition, inflammation, and death prediction in HD patients. Targeting PTX3 may reduce the high morbidity and mortality rates associated with ESRD patients (25) , but clopidogrel should continue to be the backbone of treatment for PAD patients (26) .…”

Current Medical Therapy and Revascularization in Peripheral Artery Disease of the Lower Limbs: Impacts on Subclinical Chronic Inflammation

“…Clopidogrel is a second-generation thienopyridine and a widely prescribed prodrug with anti-thrombotic activity through the irreversible inhibition of the P2Y receptor on platelets. Clopidogrel remains a mainstay of PAD treatment, with a significant reduction in MACEs in this population [117].…”

Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries

“…It has been tested as an antiplatelet drug in clinical trials, resulting in approval as a platelet aggregation inhibitor in Italy 3–8 . Recent meta‐analyses have considered applications in prevention and prophylaxis of cardiovascular disease 9,10 . However, clinical and preclinical studies suggested that effects of picotamide are not limited to antiplatelet activity, or to inhibition of thromboxane A 2 ‐mediated functions.…”