Future of antithrombotic therapy for heart failure with coronary artery disease

Coronary artery disease (CAD) is the most common cause of heart failure (HF), and antiplatelet agents should be administered in drug therapy for CAD unless contraindicated. Patients with HF often have concomitant atrial fibrillation (AF), whose incidence rate increases with HF severity; one can cause another, resulting in a vicious cycle. Furthermore, approximately 10% of patients with AF have concomitant CAD. The Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial¹ recommended anticoagulant monotherapy for patients with AF and CAD to reduce the risk of bleeding. Subgroup analysis conducted in the AFIRE trial showed that compared with combined anticoagulant and antiplatelet therapy, anticoagulant (rivaroxaban) monotherapy significantly reduced cardiovascular and major bleeding events in patients with AF/CAD complicated by HF. Conversely, the benefits of anticoagulant monotherapy over combined anticoagulant and antiplatelet therapy were not confirmed in patients with AF/CAD without HF.² Therefore, anticoagulant monotherapy is primarily recommended for patients with AF and CAD complicated by HF.

Non-steroidal anti-inflammatory drugs exert analgesic and antipyretic effects by reducing prostaglandin production. However, the suppression of prostaglandin biosynthesis in the kidney causes oedema and an increase in circulating fluid volume, which, in turn, increases cardiac workload and may worsen HF. An epidemiological study on the relationship between aspirin use and HF incidence in 30 827 people showed that aspirin use was significantly associated with HF incidence {hazard ratio 1.26 [95% confidence interval (CI): 1.12–1.41; P ≤ 0.001]}.³ Therefore, sufficient care is required when administering aspirin to patients at risk of HF.

Generally, antiplatelet agents, including aspirin, are used in HF patients with CAD and sinus rhythm. The incidence rate of concurrent AF increases with HF progression. Factor Xa inhibitors inhibit free factor Xa and factor Xa in the prothrombinase complex, thus exerting an antiplatelet effect. In addition, factor Xa inhibitors have renoprotective effects and may be considered for use in HF patients with CAD and sinus rhythm in the future. Results of large-scale clinical trials of new oral anticoagulants, such as factor XIa inhibitors, are expected to be published soon. Strategies addressing the unmet medical needs would be built based on these results.

Conflict of interest: S.A. declares having received honoraria and/or lecture fees from Bayer, Boehringer Ingelheim, and Daichi Sankyo. All other authors have declared no conflict of interest.

The authors KH and SA and are both Editors of The European Heart Journal—Cardiovascular Pharmacotherapy and were not involved in the peer review process or publication decision of this paper.

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