title: LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial.
abstract: 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.
authors.affiliation: Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Naples, Italy. michele.torella@unina2.it
authors.forename: Michele
authors.initials: M
authors.lastname: Torella
authors.forename: Daniele
authors.initials: D
authors.lastname: Torella
authors.forename: Paolo
authors.initials: P
authors.lastname: Chiodini
authors.forename: Marco
authors.initials: M
authors.lastname: Franciulli
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Romano
authors.forename: Luca
authors.initials: L
authors.lastname: De Santo
authors.forename: Marisa
authors.initials: M
authors.lastname: De Feo
authors.forename: Cristiano
authors.initials: C
authors.lastname: Amarelli
authors.forename: Ferdinando C
authors.initials: FC
authors.lastname: Sasso
authors.forename: Teresa
authors.initials: T
authors.lastname: Salvatore
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Ellison
authors.forename: Ciro
authors.initials: C
authors.lastname: Indolfi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cotrufo
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Nappi
mesh_terms: 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
chemical_list: D000925:Anticoagulants