title: Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves.
abstract: BACKGROUND
  Mechanical heart valve replacement requires lifelong anticoagulant treatment. Aspirin has proved useful in further reducing thromboembolic events when added to oral anticoagulants. However, increased (gastrointestinal) bleeding was observed at the doses previously tested for this combination in heart valve prostheses.
  
  
  METHODS
  We performed a prospective randomized trial to compare the combination of low-intensity oral anticoagulants (international normalized ratio 2.5 to 3.5) plus aspirin (100 mg/day) (arm A) versus high-intensity oral anticoagulants alone (arm B) (international normalized ratio 3.5 to 4.5). Arm A included 258 patients and arm B 245 patients. The two groups were comparable for all baseline characteristics.
  
  
  RESULTS
  The outcomes of the study were embolism, valve thrombosis, and major hemorrhage. The median follow-up was 23 months. The two treatments offered similar antithrombotic protection. The incidence of embolic episodes was 1.32 per 100 patient-years (95% confidence interval 0.53 to 2.7) for arm A and 1.48 per 100 patient-years (95% confidence interval 0.59 to 3.03) for arm B. Major hemorrhage occurred in 1.13 per 100 patient-years (95% confidence interval 0.41 to 2.45) for arm A and 2.33 per 100 patient-years (95% confidence interval 1.17 to 4.14) for arm B. Gastrointestinal bleeding was not increased by this combined reduced dose of aspirin and coumarin.
authors.affiliation: Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematólogicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: S S
authors.initials: SS
authors.lastname: Meschengieser
authors.forename: C G
authors.initials: CG
authors.lastname: Fondevila
authors.forename: J
authors.initials: J
authors.lastname: Frontroth
authors.forename: M T
authors.initials: MT
authors.lastname: Santarelli
authors.forename: M A
authors.initials: MA
authors.lastname: Lazzari
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D003374:Coumarins / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D003374:Coumarins; D010975:Platelet Aggregation Inhibitors; C030123:coumarin; D001241:Aspirin