Author + information
- Received January 4, 2018
- Revision received March 12, 2018
- Accepted March 14, 2018
- Published online June 11, 2018.
- John D. Puskas, MD, MSca,∗ (, )
- Marc Gerdisch, MDb,
- Dennis Nichols, MDc,
- Lilibeth Fermin, MDd,
- Birger Rhenman, MDd,
- Divya Kapoor, MDd,
- Jack Copeland, MDe,
- Reed Quinn, MDf,
- G. Chad Hughes, MDg,
- Hormoz Azar, MDh,
- Michael McGrath, MDh,
- Michael Wait, MDi,
- Bobby Kong, MDj,
- Tomas Martin, MDk,
- E. Charles Douville, MDl,
- Steven Meyer, MD, PhDm,
- Jian Ye, MD MScn,
- W.R. Eric Jamieson, MDo,
- Lance Landvater, MDp,
- Robert Hagberg, MDq,
- Timothy Trotter, MDr,
- John Armitage, MDs,
- Jeffrey Askew, MDs,
- Kevin Accola, MDt,
- Paul Levy, MDu,
- David Duncan, MDv,
- Bobby Yanagawa, MD, PhDw,
- John Ely, MSx,
- Allen Graeve, MDc,
- for the PROACT Investigators∗
- aIcahn School of Medicine at Mount Sinai, New York, New York
- bFranciscan St. Francis Health, Indianapolis, Indiana
- cMulticare Tacoma General, Tacoma, Washington
- dSouthern Arizona Veterans Affairs Hospital, Tucson, Arizona
- eUniversity of Arizona, Tucson, Arizona
- fMaine Medical, Portland, Maine
- gDuke University, Durham, North Carolina
- hSentara Norfolk General, Norfolk, Virginia
- iUniversity of Texas Southwestern, Dallas, Texas
- jSt. Joseph Mercy Hospital, Ann Arbor, Michigan
- kUniversity of Florida, Gainesville, Florida
- lProvidence Portland, Portland, Oregon
- mUniversity of Alberta, Edmonton, Alberta, Canada
- nSt. Paul’s Hospital, Vancouver, British Columbia, Canada
- oVancouver General Hospital, Vancouver, British Columbia, Canada
- pCarolina Cardiovascular, Raleigh, North Carolina
- qHartford Hospital, Hartford, Connecticut
- rOklahoma City VA, Oklahoma City, Oklahoma
- sMary Washington, Fredericksburg, Virginia
- tFlorida Hospital, Orlando, Florida
- uNew Mexico Heart Institute, Albuquerque, New Mexico
- vNovant Health Forsyth Medical Center, Winston-Salem, North Carolina
- wSt. Michael’s Hospital, Toronto, Ontario, Canada
- xOn-X Life Technologies, Austin, Texas
- ↵∗Address for correspondence:
Dr. John D. Puskas, Department of Cardiovascular Surgery, Mount Sinai Saint Luke’s, Mount Sinai Beth Israel and Mount Sinai West, 1111 Amsterdam Avenue, 6th Floor Babcock Building, New York, New York 10029.
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)
PROACT was funded by On-X Life Technologies, manufacturer of the On-X valve, and was conducted under an investigational device exemption provided by the U.S. Food and Drug Administration. The sponsor played no role in the decision to submit the manuscript for publication. An academic steering committee designed the trial and was responsible for oversight of study conduct and reporting of all results and takes responsibility for the accuracy and completeness of the data analyses. Dr. Gerdish is a consultant for CryoLife. Dr. Quinn is an advisor for On-X and LivaNova. Dr. McGrath is a consultant for Abbott. Dr. Martin is a consultant for Johnson & Johnson; and an advisor for Medtronic. Dr. Accola has received speaking fees from Edwards Lifesciences. Dr. Ely was an employee of On-X at the time of the trial. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John W.A. Eikelboom, MD, served as Guest Editor for this paper.
- Received January 4, 2018.
- Revision received March 12, 2018.
- Accepted March 14, 2018.
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