Do Oral Factor Xa Inhibitors have a Role in Patients with Mechanical Heart Valves?

Mechanical heart valves (MHVs) replacement is recommended for younger patients with valvular heart disease because of the durability of the mechanical valve, but these patients need antithrombotic therapy for a lifelong time. The vitamin K antagonist (VKA) warfarin is the only approved oral antithrombotic drug for patients with MHVs. The direct oral anticoagulants (DOACs), including direct thrombin inhibitors and factor Xa (FXa) inhibitors, present some advantages over warfarin, such as weak interaction with drugs, no need for routine monitoring of coagulation function, and no frequent adjustment of medication dose. DOACs have been approved in the antithrombotic treatment of venous thromboembolism and nonvalvular atrial fibrillation. However, the application of thrombin inhibitors in patients with MHV is contraindicated because of the RE-ALIGN trial results, and FXa inhibitors are not recommended. Considering the mechanism underlying coagulation, it may be more efficient to inhibit the upstream coagulation FXa than thrombin. Recently, several preclinical and clinical investigations have looked into the role of FXa inhibitors in patients with MHVs, and have provided some encouraging evidence. Herein, we review the completed and ongoing clinical trials, and express our opinion that the following patients with a low risk of thromboembolic events should be considered for treatment with FXa inhibitors: patients with MHVs replacement 3 months postoperatively, patients with isolated aortic valve replacement, patients with a new, low thrombogenicity mechanical valve, and Asian patients. We hope this summary will provide meaningful insights for further clinical investigations.