LAUSR

OBJECTIVE To perform a systematic literature review and indirect treatment comparison (ITC) to identify, summarize, and quantify randomized controlled trial (RCT) evidence evaluating combination anticoagulant or P2Y12 inhibitor with low dose aspirin versus low dose aspirin alone for the prevention of atherothrombotic events in patients with stable coronary artery disease (CAD) and/or peripheral artery disease (PAD). METHODS We performed an updated search of CENTRAL, MEDLINE and EMBASE through August 23, 2021 to identify RCTs of adult patients with chronic CAD and/or PAD that compared combination anticoagulant or P2Y12 Inhibitor with low dose aspirin to low dose aspirin alone. Outcomes of interest included major adverse cardiovascular events (MACE) including cardiovascular death, stroke, or myocardial infarction (MI) and bleeding. Outcomes were pooled using random-effects models to generate hazard or risk ratios (HRs or RRs) and accompanying 95% confidence intervals (CIs). Adjusted ITCs using subsequent pooled HRs/RRs were then performed. RESULTS Six publications reporting the results of two unique RCTs (one evaluating clopidogrel + aspirin vs. aspirin alone and the other rivaroxaban 2.5 mg twice daily + aspirin vs. aspirin alone) were analyzed. ITC suggested rivaroxaban + aspirin was associated with a lower risk of MACE compared with clopidogrel + aspirin (HR =0.82, 95%CI =0.68-0.98). When looking at the individual components of the MACE, rivaroxaban + aspirin was associated with lower risk of cardiovascular death (HR =0.75, 95%CI =0.57-0.98) and stroke (RR =0.67, 95 CI =0.49-0.93) and similar risk of MI (RR =0.93, 95%CI =0.70-1.23) versus clopidogrel + aspirin. No evidence of a difference in moderate-to-severe bleeding, fatal bleeding, or intracranial hemorrhage (ICH) was seen between the two treatment strategies. CONCLUSIONS Compared to clopidogrel + low dose aspirin, the use of rivaroxaban 2.5 mg twice daily + low dose aspirin reduced the risk of MACE, CV death and stroke including ischemic stroke in patients with or at high risk for chronic CAD and/or PAD. These benefits of rivaroxaban 2.5 mg twice daily + low dose aspirin compared to clopidogrel + low-dose aspirin appear to be achieved without significantly increasing patients' risk of moderate-to-severe including ICH or fatal bleeding.