Recommendations for Antithrombotic Therapy for Patients with Prosthetic Heart Valves

CORLOERecommendationsComment/Rationale
IAAnticoagulation with a VKA and INR monitoring is recommended in patients with a mechanical prosthetic valve (178–183).2014 recommendation remains current.
IBAnticoagulation with a VKA to achieve an INR of 2.5 is recommended for patients with a mechanical bileaflet or current-generation single-tilting disc AVR and no risk factors for thromboembolism (178,184–186).2014 recommendation remains current.
IBAnticoagulation with a VKA is indicated to achieve an INR of 3.0 in patients with a mechanical AVR and additional risk factors for thromboembolic events (AF, previous thromboembolism, LV dysfunction, or hypercoagulable conditions) or an older-generation mechanical AVR (such as ball-in-cage) (178).2014 recommendation remains current.
IBAnticoagulation with a VKA is indicated to achieve an INR of 3.0 in patients with a mechanical MVR (178,187,188).2014 recommendation remains current.
IAAspirin 75 mg to 100 mg daily is recommended in addition to anticoagulation with a VKA in patients with a mechanical valve prosthesis (178,189,190).2014 recommendation remains current.
IIaBAspirin 75 mg to 100 mg per day is reasonable in all patients with a bioprosthetic aortic or mitral valve (178,191–194).2014 recommendation remains current.
IIaB-NRAnticoagulation with a VKA to achieve an INR of 2.5 is reasonable for at least 3 months and for as long as 6 months after surgical bioprosthetic MVR or AVR in patients at low risk of bleeding (195–197).MODIFIED: LOE updated from C to B-NR. Anticoagulation for all surgical tissue prostheses was combined into 1 recommendation, with extension of the duration of anticoagulation up to 6 months. Stroke risk and mortality rate are lower in patients who receive anticoagulation for up to 6 months after implantation of a tissue prosthesis than in those who have do not have anticoagulation. Anticoagulation for a tissue prosthesis is also supported by reports of valve thrombosis for patients undergoing bioprosthetic surgical AVR or MVR, a phenomenon that may be warfarin responsive.
See Online Data Supplement 6.
Many patients who undergo implantation of a surgical bioprosthetic MVR or AVR will not require life-long anticoagulation. However, there is an increased risk of ischemic stroke early after operation, particularly in the first 90 to 180 days after operation with either a bioprosthetic AVR or MVR (198–205). Anticoagulation early after valve implantation is intended to decrease the risk of thromboembolism until the prosthetic valve is fully endothelialized. The potential benefit of anticoagulation therapy must be weighed against the risk of bleeding. In a nonrandomized study, patients with a bioprosthetic MVR who received anticoagulation had a lower rate of thromboembolism than those who did not receive therapy with VKA (2.5% per year with anticoagulation versus 3.9% per year without anticoagulation; p=0.05) (193). Even with routine anticoagulation early after valve surgery, the incidence of ischemic stroke within the first 30 postoperative days was higher after replacement with a biological prosthesis (4.6%±1.5%) than after mitral valve repair (1.5%±0.4%) or replacement with a mechanical prosthesis (1.3%±0.8%; p<0.001) (206). Small RCTs have not established a convincing net benefit of anticoagulation after implantation of a bioprosthetic AVR (205,207); however, a large observational Danish registry demonstrated a lower risk of stroke and death with VKA extending up to 6 months, without a significantly increased bleeding risk (197). Concern has also been raised about a higher-than-recognized incidence of bioprosthetic valve thrombosis leaflets after surgical valve replacement (196). Thus, anticoagulation with an INR target of 2.5 may be reasonable for at least 3 months and perhaps for as long as 6 months after implantation of a surgical bioprosthetic MVR or AVR in patients at low risk of bleeding. Compared with oral anticoagulation alone, the addition of dual-antiplatelet therapy results in at least a 2- to 3-fold increase in bleeding complications, and the recommendations on triple therapy should be followed (208).
IIbB-RA lower target INR of 1.5 to 2.0 may be reasonable in patients with mechanical On-X AVR and no thromboembolic risk factors (209).NEW: A lower target INR was added for patients with a mechanical On-X AVR and no thromboembolic risk factors treated with warfarin and low-dose aspirin. A single RCT of lower- versus standard-intensity anticoagulation in patients undergoing On-X AVR showed equivalent outcomes, but the bleeding rate in the control group was unusually high.
See Online Data Supplement 6.
In patients without risk factors who receive a mechanical On-X aortic heart valve (On-X Life Technologies Inc., Austin, Texas), a lower INR target of 1.5 to 2.0 (in conjunction with aspirin 81 mg daily) may be considered for long-term management, beginning 3 months after surgery. Warfarin dosing is targeted to an INR of 2.5 (range 2.0 to 3.0) for the first 3 months after surgery (209). This is based on a single RCT of lower- versus standard-intensity anticoagulation in patients undergoing On-X AVR, showing equivalent outcomes. The control arm did have a bleeding rate of 3.2% per patient-year (209).
IIbB-NRAnticoagulation with a VKA to achieve an INR of 2.5 may be reasonable for at least 3 months after TAVR in patients at low risk of bleeding (203,210,211).NEW: Studies have shown that valve thrombosis may develop in patients after TAVR, as assessed by multidetector computerized tomographic scanning. This valve thrombosis occurs in patients who received antiplatelet therapy alone but not in patients who were treated with VKA.
See Online Data Supplement 6.
Several studies have demonstrated the occurrence of prosthetic valve thrombosis after TAVR, as assessed by multidetector computerized tomography, which shows reduced leaflet motion and hypo-attenuating opacities. The incidence of this finding has varied from 7% to 40%, depending on whether the patients are from a clinical trial or registry and whether some patients received anticoagulation with VKA (203,210,211). Up to 18% of patients with a thrombus formation developed clinically overt obstructive valve thrombosis (210). A post-TAVR antithrombotic regimen without warfarin seems to predispose patients to the development of valve thrombosis (203,210). The utility of the DOACs in this population is unknown at this time.
IIbCClopidogrel 75 mg daily may be reasonable for the first 6 months after TAVR in addition to life-long aspirin 75 mg to 100 mg daily.2014 recommendation remains current.
III: HarmBAnticoagulant therapy with oral direct thrombin inhibitors or anti-Xa agents should not be used in patients with mechanical valve prostheses (200,212,213).2014 recommendation remains current.