Efficacy and safety of low dose rivaroxaban in patients with coronary heart disease: a systematic review and meta-analysis

The mortality effects and risk–benefit profile of low dose rivaroxaban (2.5 mg twice daily) in patients with coronary heart disease are not completely understood. Five randomized controlled trials (26,110 patients) were selected using PubMed and Cochrane library till April 2019. The background antiplatelet therapy was aspirin in 3 trials, P2Y12 inhibitor in 1 trial, and in 1 trial 65% patients received aspirin and 35% were on dual antiplatelet therapy (DAPT). The outcomes of interest were cardiovascular mortality, all-cause mortality, myocardial infarction (MI), stroke and major bleeding events. Random effects hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Low dose rivaroxaban did not reduce the risk of cardiovascular mortality (HR 0.90, 95% CI 0.73–1.11, P = 0.34) or all-cause mortality (HR 0.91, 95% CI 0.74–1.12, P = 0.38) compared with control. However, low dose rivaroxaban was associated with reduction in MI (HR 0.85, 95% CI 0.73–0.99, P = 0.04), and stroke (HR 0.59, 95%CI 0.48–0.73, P < 0.001) at the expense of major bleeding (HR 1.64, 95% CI 1.39–1.94, P < 0.001) compared with control. These effects did not vary according to acute coronary syndrome or stable coronary heart disease (P-interaction > 0.05). The use of low dose rivaroxaban in patients with coronary heart disease predominantly receiving antiplatelet monotherapy did not reduce cardiovascular or all-cause mortality. The benefits of preventing MI and stroke were balanced by increased risk of major bleeding.