For how long can anticoagulation (AC) therapy be given to patients with bioprosthetic valves?

Duration of Anticoagulation for Bioprosthetic Valves

Anticoagulation with warfarin (INR 2.0-3.0) should be given for at least 3 months and may be extended up to 6 months after bioprosthetic valve replacement in patients at low bleeding risk, followed by indefinite low-dose aspirin (75-100 mg daily) for those without additional risk factors. 1, 2

Standard Duration Based on Valve Position

Surgical Bioprosthetic Valves (Aortic or Mitral)

• Warfarin therapy (INR 2.5, range 2.0-3.0) for 3-6 months is the ACC/AHA Class IIa recommendation for both aortic and mitral bioprosthetic valve replacements 1
• The rationale is that stroke risk is substantially elevated during the first 90-180 days post-operatively, with incidence rates of 4.6% within 30 days for bioprosthetic valves 1
• A large Danish registry study of 4,075 patients demonstrated that discontinuing warfarin within 6 months was associated with significantly higher cardiovascular death (adjusted IRR 7.61 for 30-89 days; 3.51 for 90-179 days) 3

TAVR (Transcatheter Aortic Valve Replacement)

• Dual antiplatelet therapy (aspirin 75-100 mg plus clopidogrel 75 mg) for 6 months is the standard approach, though this is based on clinical trial protocols rather than direct evidence 1, 4
• Warfarin for at least 3 months may be reasonable as an alternative, particularly given that subclinical valve thrombosis occurs in 7-40% of TAVR patients on antiplatelet therapy alone but not in those receiving warfarin 4

Long-Term Management After Initial Period

Patients WITHOUT Additional Risk Factors

• Transition to indefinite low-dose aspirin (75-100 mg daily) alone after completing the 3-6 month warfarin course 1, 2
• This applies to patients in sinus rhythm with normal left ventricular function and no history of thromboembolism 1

Patients WITH Additional Risk Factors Requiring Indefinite Anticoagulation

Continue warfarin indefinitely (INR 2.5, range 2.0-3.0) plus aspirin 75-100 mg daily for patients with: 2, 4

• Atrial fibrillation 1
• History of thromboembolism 1
• Left ventricular dysfunction 1
• Hypercoagulable conditions 1, 2
• Enlarged left atrium 2

Critical Evidence Considerations

ESC vs ACC/AHA Guideline Differences

The European Society of Cardiology (ESC) 2017 guidelines are more conservative, recommending only 3 months of warfarin for surgical tricuspid valve replacement (Class IIa) and considering it for aortic valve replacement (Class IIb), while not recommending indefinite aspirin 1. However, the ACC/AHA 2017 guidelines provide stronger evidence (Class IIa, Level B-NR) for the extended 3-6 month duration based on the Danish registry data showing lower stroke and mortality rates 1.

Challenges with Warfarin Management

• In the ANSWER Registry of 386 patients, 20% failed to reach therapeutic INR levels, and among those who did, 78% had at least one subtherapeutic value during follow-up 5
• Patients on warfarin had substantially higher bleeding rates (12% vs 3%) compared to those not anticoagulated, with no difference in embolic events (2.8% vs 3.1%) 5
• Supratherapeutic INR values conferred a 7-fold higher risk for bleeding events 5

Bioprosthetic Valve Thrombosis Considerations

• If confirmed bioprosthetic valve thrombosis occurs, indefinite warfarin anticoagulation should be strongly considered as recurrent thrombosis occurs in 23% of patients after a median of 23 months, though this must be balanced against increased bleeding risk 6
• Echocardiography normalizes in 75% of BPVT patients within 3 months of anticoagulation 6

Critical Contraindications

Direct oral anticoagulants (DOACs) including rivaroxaban, apixaban, and dabigatran are contraindicated for any prosthetic valve due to excessive thrombotic complications demonstrated in the GALILEO trial, which was terminated early for harm 1, 2, 4. A small retrospective study suggested similar rates of events with DOACs versus warfarin, but this was underpowered and contradicts the definitive GALILEO trial results 7.

Common Pitfalls to Avoid

• Do not discontinue warfarin before 3 months unless there is prohibitive bleeding risk, as the highest thromboembolic risk period is 0-180 days post-operatively 1, 3
• Do not use DOACs as a substitute for warfarin in the early post-operative period 1, 2, 4
• Do not forget to assess for additional risk factors that would mandate indefinite anticoagulation beyond the initial 3-6 month period 1, 2
• Monitor INR closely as achieving and maintaining therapeutic levels is challenging, with frequent subtherapeutic and supratherapeutic excursions 5