LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial.
BACKGROUND
Moderate anticoagulation after mechanical heart valve replacement has been proposed to reduce the risk of bleeding related to lifelong anticoagulation. However, the efficacy of such reduced antithrombotic regimens is still unknown. The present prospective open-label, single-center, randomized controlled trial aimed to evaluate the safety and feasibility of reduced oral anticoagulation after isolated mechanical aortic valve replacement.


METHODS
Low-risk patients undergoing bileaflet mechanical aortic valve replacement were randomized to a low International normalized ratio (INR) target (1.5-2.5; LOW-INR group) or to the standard currently recommended INR (2.0-3.0; CONVENTIONAL-INR group) through daily coumarine oral therapy. No aspirin was added. Median follow-up was 5.6 years. The primary outcome was assessment of noninferiority of the low over the standard anticoagulation regimen on thromboembolic events. Secondary end point was the superiority of the reduced INR target strategy on bleeding events.


RESULTS
We analyzed 396 patients (197 in the LOW-INR group and 199 in the CONVENTIONAL-INR group). The mean of INR was 1.94 +/- 0.21 and 2.61 +/- 0.25 in the LOW-INR and CONVENTIONAL-INR groups, respectively (P < .001). One versus three thromboembolic events occurred in the LOW-INR and CONVENTIONAL-INR, respectively, meeting the noninferiority criterion (P = .62). Total hemorrhagic events occurred in 6 patients in the LOW-INR group and in 16 patients in the CONVENTIONAL-INR group (P = .04).


CONCLUSIONS
LOWERING-IT trial established that the proposed LOW-INR target is safe and feasible in low-risk patients after bileaflet aortic mechanical valve replacement. It results in similar thrombotic events and in a significant reduction of bleeding occurrence when compared to the conventional anticoagulation regimen.
Torella
Michele
M
Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Naples, Italy. michele.torella@unina2.it
Torella
Daniele
D
Chiodini
Paolo
P
Franciulli
Marco
M
Romano
Giampaolo
G
De Santo
Luca
L
De Feo
Marisa
M
Amarelli
Cristiano
C
Sasso
Ferdinando C
FC
Salvatore
Teresa
T
Ellison
Georgina M
GM
Indolfi
Ciro
C
Cotrufo
Maurizio
M
Nappi
Gianantonio
G
D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001024:Aortic Valve Stenosis / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006350:Heart Valve Prosthesis; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D011379:Prognosis; D011446:Prospective Studies; D011474:Prosthesis Design; D012307:Risk Factors; D013927:Thrombosis / Q000188:drug therapy; D055815:Young Adult
D000925:Anticoagulants