title: 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.
abstract: 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.
authors: Department of Cardiothoracic Surgery, Emory University, Atlanta, Ga. Electronic address: jpuskas@emory.edu.
authors: John
authors: J
authors: Puskas
authors: Department of Cardiothoracic Surgery, Franciscan St Francis Health, Indianapolis, Ind.
authors: Marc
authors: M
authors: Gerdisch
authors: Department of Cardiothoracic Surgery, Multicare Tacoma General, Tacoma, Wash.
authors: Dennis
authors: D
authors: Nichols
authors: Department of Cardiothoracic Surgery, Maine Medical, Portland, Maine.
authors: Reed
authors: R
authors: Quinn
authors: Department of Cardiothoracic Surgery, Multicare Tacoma General, Tacoma, Wash.
authors: Charles
authors: C
authors: Anderson
authors: Department of Cardiothoracic Surgery, Southern Arizona Veterans Affairs Hospital, Tucson, Ariz.
authors: Birger
authors: B
authors: Rhenman
authors: Department of Cardiothoracic Surgery, Southern Arizona Veterans Affairs Hospital, Tucson, Ariz.
authors: Lilibeth
authors: L
authors: Fermin
authors: Department of Cardiothoracic Surgery, Sentara Norfolk General Hospital, Norfolk, Va.
authors: Michael
authors: M
authors: McGrath
authors: Department of Cardiothoracic Surgery, St Joseph Mercy Hospital, Ypsilanti, Mich.
authors: Bobby
authors: B
authors: Kong
authors: Department of Cardiothoracic Surgery, Duke University, Durham, NC.
authors: Chad
authors: C
authors: Hughes
authors: Department of Cardiothoracic Surgery, University of Arizona, Tucson, Ariz.
authors: Gulshan
authors: G
authors: Sethi
authors: Department of Cardiothoracic Surgery, University of Texas, Dallas, Tex.
authors: Michael
authors: M
authors: Wait
authors: Department of Cardiothoracic Surgery, University of Florida, Gainesville, Fla.
authors: Tomas
authors: T
authors: Martin
authors: Department of Cardiothoracic Surgery, Multicare Tacoma General, Tacoma, Wash.
authors: Allen
authors: A
authors: Graeve
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D001021:Aortic Valve / Q000601:surgery*; D001241:Aspirin / Q000008:administration & dosage*; D005260:Female; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013923:Thromboembolism / Q000209:etiology* / Q000517:prevention & control*; D014481:United States; D014486:United States Food and Drug Administration; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D001241:Aspirin