Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement.
anticoagulation; dual-antiplatelet therapy; mechanical aortic valve replacement; thromboembolism
BACKGROUND: The burden oral anticoagulation is a limitation of mechanical valve prostheses.
OBJECTIVES: The aim of this study was to test whether patients could be safely managed with dual-antiplatelet therapy (DAPT) (aspirin 325 mg and clopidogrel 75 mg) or lower warfarin after On-X mechanical aortic valve replacement (mAVR).
METHODS: PROACT (Prospective Randomized On-X Anticoagulation Trial) (n = 576) is a multicenter (41 sites) noninferiority trial. From June 2006 through February 2014, 201 patients ≥18 years of age without thromboembolic risk factors undergoing mAVR were randomized to receive DAPT (n = 99) or standard warfarin plus aspirin (n = 102) 3 months after mAVR (low-risk arm). From June 2006 through October 2009, 375 patients with 1 or more thromboembolic risk factors were also randomized to lower intensity warfarin plus aspirin (international normalized ratio 1.5 to 2.0; n = 185) or standard warfarin plus aspirin (international normalized ratio 2.0 to 3.0; n = 190) 3 months after mAVR (high-risk arm).
RESULTS: The low-risk arm was terminated for excess cerebral thromboembolic events (3.12% per patient-year vs. 0.29% per patient-year, p = 0.02) in the DAPT group at up to 8.8-year follow-up (631.6 patient-years), with no differences in bleeding or all-cause mortality. High-risk arm patients experienced significantly lower major (1.59% per patient-year vs. 3.94% per patient-year, p = 0.002) and minor (1.27% per patient-year vs. 3.49% per patient-year, p = 0.002) bleeding up to 8.7-year follow-up (2,035.2 patient-years), with no differences in thromboembolism (0.42% per patient-year vs. 0.09% per patient-year, p = 0.20) and all-cause mortality.
CONCLUSIONS: DAPT was associated with higher rates of thromboembolism and valve thrombosis compared with control in the low-risk arm. International normalized ratios were safely maintained at 1.5 to 2.0 in high-risk patients, without differences in mortality or thromboembolic complications. (Randomized On-X Anticoagulation Trial [PROACT]; NCT00291525).
Puskas, John D; Gerdisch, Marc; Nichols, Dennis; Fermin, Lilibeth; Rhenman, Birger; Kapoor, Divya; Copeland, Jack; Quinn, Reed; Hughes, G Chad; Azar, Hormoz; McGrath, Michael; Wait, Michael; Kong, Bobby; Martin, Tomas; Douville, E Charles; Meyer, Steven; Ye, Jian; Jamieson, W R Eric; Landvater, Lance; Hagberg, Robert; Trotter, Timothy; Armitage, John; Askew, Jeffrey; Accola, Kevin; Levy, Paul; Duncan, David; Yanagawa, Bobby; Ely, John; and Graeve, Allen, "Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement." (2018). Articles, Abstracts, and Reports. 846.