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 thromboembolismwere randomized at 33 US centers to receive lower dosewarfarin (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.