Antithrombotic and proton pump inhibitor co-therapy in patients with atrial fibrillation and stable coronary disease: a post hoc analysis of the AFIRE trial

Background Among patients with atrial fibrillation (AF) and stable coronary artery disease, bleeding events increased the cardiovascular events and mortality. We aimed to evaluate the effect of proton pump inhibitor (PPI) on the risk of bleeding events in these patients. Methods In the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease), patients with non-valvular AF and coronary artery disease were recruited and randomized to receive the rivaroxaban monotherapy or combination therapy with rivaroxaban plus antiplatelet drug. The present sub-analysis evaluated the risks of any bleeding events. Results Among 2,225 patients, 1,357 (61.3%) were receiving a PPI at baseline. During follow-up, 384 bleeding events were occurred, and incidence of bleeding events were significantly lower in patients with PPI compared with those without PPI (p=0.03). Among combination therapy with rivaroxaban plus antiplatelet, effect of PPI for cumulative incidence of bleeding events were significantly different between groups (p=0.01), however, these differences were not shown among rivaroxaban monotherapy patients (p=0.50, Figure 1). Multivariate Cox hazard analysis showed that PPI use had significantly lower risk of bleeding events (hazard risk 0.79, 95% confidence interval 0.64–0.97, p=0.03). In addition to PPI, male, heart failure and combination therapy with rivaroxaban plus antiplatelet drug were independent predictors of bleeding events. Conclusions PPI use was significantly associated with lower risk of bleeding events among patients with AF and stable coronary artery disease. Especially, for patients at high bleeding risk, such as receiving both anticoagulant and antiplatelet drugs, PPI is useful to reduce bleeding events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The Japan Cardiovascular Foundation through a contract with Bayer Yakuhin.