The Optimal Management of Anti-Thrombotic Therapy After Valve Replacement: Certainties and Uncertainties


This manuscript reviews the optimal management of antithrombotic therapy following valve replacement surgery. The following are 10 key points from the review:

1. Patients with mechanical heart valve replacements require life-long anticoagulation. Use of antiplatelet medications does not provide adequate protection against thromboembolic risk. The combination of low-dose aspirin and vitamin K antagonists (VKAs) is recommended for all patients with mechanical valve prostheses by the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines (selective aspirin use per the American College of Chest Physicians [ACCP] and European Society of Cardiology [ESC]/European Association for Cardio-Thoracic Surgery [EACTS] guidelines).

2. Bioprosthetic valves avoid the need for life-long anticoagulation.

3. Guidelines recommend the use of a target international normalized ratio (INR) range of 2.5 for aortic mechanical prosthetic valves without additional risk factors for thromboembolism (e.g., atrial fibrillation, prior thromboembolism, left ventricular dysfunction, and hypercoagulable states). Guidelines recommend the use of a target INR range of 3.0 (or 3.5) for mitral mechanical prosthetic valves and any aortic valve prosthesis associated with thromboembolic risk factors.

4. INR variability and poor INR control are associated with increased mortality risk. VKA management in an anticoagulation clinic allows for optimal INR monitoring and VKA dose adjustment. While some degree of INR variability is dictated by genetic polymorphisms of cytochrome P450 2C9, genotyping of patients treated with VKA is not currently recommended.

5. In patients with an elevated INR (>6.0) but no severe bleeding, management includes transient withdrawal of the anticoagulant and administration of oral vitamin K according to the actual and target INR values. Patients with severe bleeding should be treated with immediate anticoagulant reversal (usually prothrombin concentrates or fresh frozen plasma) and vitamin K.

6. In patients with mechanical valve prosthesis who experience an acute coronary syndrome requiring intracoronary stenting, 3-6 months of triple antithrombotic therapy (VKA, aspirin, and a P2Y12 inhibitor) are recommended. The combination of clopidogrel and VKA without aspirin should be considered because it may decrease the risk of bleeding without a significantly increased risk of thromboembolism.

7. Direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) should not be used in patients with mechanical valve prostheses because of the increased risk of valve thrombosis. The presence of a bioprosthetic valve was an exclusion from all major trials of direct oral anticoagulants, so their safety in this population is unknown. Thus, avoiding use of direct oral anticoagulants in patients with atrial fibrillation or venous thromboembolism is advised.

8. Thromboembolism risk is up to 10 times higher in the first month following valve replacement surgery. Use of heparin 12-24 hours following surgery is recommended. Use of either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) is reasonable. Use of low-dose aspirin can lower the thromboembolic risk while increasing the bleeding risk postoperatively. Anticoagulation with VKA is recommended for the first 3 months in most patients receiving a bioprosthetic valve. ESC/EACTS and ACCP guidelines offer the option of aspirin therapy in the first 3 months following a bioprosthetic aortic valve replacement. ACC/AHA and ACCP guidelines recommend the use of aspirin beyond 3 months in all patients with bioprosthetic valves.

9. Patients with mechanical valve prostheses who undergo noncardiac surgery can often be performed safely without interruption of VKA therapy if they are at low risk for bleeding (e.g., dental care, ophthalmologic and demographic surgery, many gastrointestinal endoscopic procedures). In patients undergoing major surgery, the INR should be <1.5 and heparin bridging is advised for high-risk patients only (mitral valve prostheses or patients with aortic valve prostheses and thromboembolic risk factors). Heparin bridging is not required for aortic valve prostheses without thromboembolic risk factors. Use of either UFH or LMWH is reasonable when bridging is indicated.

10. In patients undergoing transcatheter aortic valve replacement (TAVR), guidelines recommend indefinite low-dose aspirin long-term and aspirin plus clopidogrel (or another thienopyridine) for the first 1-3 months.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Pulmonary Hypertension and Venous Thromboembolism, Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Anticoagulation Management and Venothromboembolism, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Vitamin K, Cytochrome P-450 Enzyme System, Dental Care, Acute Coronary Syndrome, Anticoagulants, Demography, Heparin, Low-Molecular-Weight, Heparin, Venous Thromboembolism, American Heart Association, Risk Factors, Ticlopidine, Pyridines, Prothrombin, Thoracic Surgery, Aspirin, Fibrinolytic Agents, Prostheses and Implants, Polymorphism, Genetic, Aortic Valve, Atrial Fibrillation, Ventricular Dysfunction, Left, Mitral Valve

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