What are the recommendations for using new anticoagulants, such as Direct Oral Anticoagulants (DOACs) like apixaban (apixaban) and rivaroxaban (rivaroxaban), in patients with mechanical heart valves?

Direct Oral Anticoagulants (DOACs) Are Contraindicated in Patients with Mechanical Heart Valves

DOACs including apixaban, rivaroxaban, dabigatran, and edoxaban are absolutely contraindicated in patients with mechanical heart valves and should never be used in this population. Warfarin remains the only approved oral anticoagulant for these patients and must be used lifelong 1, 2.

Evidence Against DOACs in Mechanical Valves

Clinical Trial Data

• The RE-ALIGN trial demonstrated increased thromboembolic and bleeding complications with dabigatran compared to warfarin in patients with mechanical heart valves, leading to early termination 1, 2
• A 2023 trial of apixaban versus warfarin in patients with On-X mechanical aortic valves was stopped early after enrolling 863 participants due to excess thromboembolic events in the apixaban group (4.2%/patient-year vs 1.3%/patient-year with warfarin), failing to meet noninferiority criteria 3
• The apixaban trial showed 20 primary endpoint events (valve thrombosis or thromboembolism) in the apixaban group versus only 6 in the warfarin group 3

Guideline Recommendations

• The ACC/AHA explicitly states that dabigatran is contraindicated (Class III: Harm, Level B-R) in patients with mechanical valve prostheses 1, 2
• Anti-Xa DOACs (rivaroxaban, apixaban, edoxaban) have not been adequately assessed and are not recommended (Class III: Harm, Level C-EO) for mechanical valves 1, 2
• The 2019 AHA/ACC/HRS guidelines define exclusion criteria for DOAC use as moderate-to-severe mitral stenosis or mechanical heart valves 1

Appropriate Anticoagulation for Mechanical Valves

Warfarin Dosing by Valve Type and Position

Mechanical Aortic Valve:

• Without additional risk factors: Target INR 2.5 (range 2.0-3.0) 1, 4
• With risk factors (atrial fibrillation, prior thromboembolism, LV dysfunction, hypercoagulable state) or older-generation prosthesis: Target INR 3.0 (range 2.5-3.5) 1

Mechanical Mitral Valve:

• All patients: Target INR 3.0 (range 2.5-3.5) regardless of risk factors 1, 2

Monitoring Requirements

• INR should be checked at least weekly during warfarin initiation 1, 4
• Once stable and in therapeutic range, INR monitoring should occur at least monthly 1, 4

Adjunctive Antiplatelet Therapy

• Addition of low-dose aspirin (75-100 mg daily) to warfarin may be considered for all patients with mechanical valves when bleeding risk is low 1, 2
• For patients experiencing stroke or systemic embolism despite therapeutic INR, consider increasing the INR goal or adding aspirin 75-100 mg daily after assessing bleeding risk 2

Special Consideration: On-X Aortic Valve

• For patients with a mechanical On-X aortic valve replacement without thromboembolic risk factors, a lower INR target of 1.5-2.0 may be reasonable starting ≥3 months after surgery, with continuation of aspirin 75-100 mg daily 1, 2
• However, the 2023 apixaban trial demonstrated this valve type still requires warfarin, not DOACs 3

Common Pitfalls to Avoid

• Never substitute a DOAC for warfarin in mechanical valve patients, even with newer valve designs like On-X, as recent trial data confirms increased thrombotic risk 3
• Do not confuse mechanical valves with bioprosthetic valves—bioprosthetic valves (including TAVR) do not have the same contraindication to DOACs 1
• Patients with moderate-to-severe mitral stenosis also require warfarin rather than DOACs, even without a prosthetic valve 1, 5
• Assess for drug-drug and drug-food interactions when prescribing warfarin, as these significantly affect INR stability 4
• Ensure lifelong anticoagulation commitment, as all mechanical valves require permanent anticoagulation 1, 2