Reduced anticoagulation after mechanical aortic valve replacement: Interim results from the Prospective Randomized On-X Valve Anticoagulation Clinical Trial randomized Food and Drug Administration investigational device exemption trial

Objective Under Food and Drug Administration investigational device exemption, the Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) has been testing the safety of less aggressive anticoagulation than recommended by the American College of Cardiology/American Heart Association guidelines after implantation of an approved bileaflet mechanical valve. Methods In this first limb of the PROACT, patients with elevated risk factors for thromboembolism were randomized at 33 US centers to receive lower dose warfarin (test international normalized ratio [INR], 1.5-2.0) or continue standard warfarin (control INR, 2.0-3.0), 3 months after mechanical aortic valve replacement. The INR was adjusted by home monitoring; all patients received 81 mg aspirin daily. Adverse events were independently adjudicated. Results A total of 375 aortic valve replacement patients were randomized into control (n = 190) and test (n = 185) groups from September 2006 to December 2009. The mean age ± standard deviation was 55.2 ± 12.5 years; 79% were men; and 93% were in sinus rhythm preoperatively. Calcific degeneration was present in 67%; active endocarditis was excluded. Concomitant procedures included coronary artery bypass grafting (27%), aortic aneurysm repair (14%), and other (25%). The follow-up duration averaged 3.82 years (755.7 patient-years [pt-yrs] for control; 675.2 pt-yrs for test). The mean INR was 2.50 ± 0.63 for the control and 1.89 ± 0.49 for the test groups (P <.0001). The test group experienced significantly lower major (1.48% vs 3.26%/pt-yr; P =.047) and minor (1.32% vs 3.41%/pt-yr; P =.021) bleeding rates. The incidence of stroke, transient ischemic attack, total neurologic events, and all-cause mortality were similar between the 2 groups. Conclusions INR can be safely maintained between 1.5 and 2.0 after aortic valve replacement with this approved bileaflet mechanical prosthesis. With low-dose aspirin, this resulted in a significantly lower risk of bleeding, without a significant increase in thromboembolism.