title: Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves.
abstract: OBJECTIVE
  Warfarin reduces risk of stroke in patients with mechanical heart valves but increases risk of hemorrhage and is difficult to use. Dabigatran etexilate, a new oral direct thrombin inhibitor, is safe and effective in reducing risk of stroke among patients with atrial fibrillation. No data exist in the setting of mechanical heart valves. We tested the hypothesis that dabigatran etexilate is as effective as heparin for thromboprophylaxis of mechanical valves in a porcine heterotopic aortic valve model.
  
  
  METHODS
  Thirty swine underwent implantation of modified bileaflet mechanical valved conduit bypassing the ligated, native descending thoracic aorta. Animals randomly received no anticoagulation (n = 10), enoxaparin 2 mg/kg subcutaneously twice daily (n = 10), or dabigatran etexilate 20 mg/kg orally twice daily. Primary end point was amount of valve thrombus at 30 days. Secondary end points included quantitative measurement of platelet deposition on valve prosthesis, thromboelastography, and hemorrhagic and embolic events.
  
  
  RESULTS
  At 30 days, we observed 638 ± 895 mg thrombus in no anticoagulation group, 121 ± 128 mg in enoxaparin group, and 19 ± 31 mg in dabigatran etexilate group (P = .01 enoxaparin vs dabigatran etexilate). Fewer platelets were deposited on valves in dabigatran etexilate group (2.7 × 10(8)) than in enoxaparin group (1.8 × 10(9), P = .03). No major or occult hemorrhagic or embolic events were observed. By thromboelastographic analysis, dabigatran etexilate produced less prolongation of K value (P = .01) and less decreases in angle (P = .01) and maximum amplitude (P = .001) than enoxaparin.
  
  
  CONCLUSIONS
  Dabigatran etexilate is as effective as enoxaparin for short-term thromboprophylaxis of mechanical valves. It prevents valve thrombus and platelet deposition at 30 days without increased adverse events. These promising results serve as a foundation for prospective clinical trials with dabigatran etexilate as an alternative to warfarin in patients with bileaflet mechanical aortic valves.
authors.affiliation: Division of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: McKellar
authors.forename: Stuart
authors.initials: S
authors.lastname: Abel
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Camp
authors.forename: Rakesh M
authors.initials: RM
authors.lastname: Suri
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ereth
authors.forename: Hartzell V
authors.initials: HV
authors.lastname: Schaff
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000991:Antithrombins / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001021:Aortic Valve / Q000601:surgery*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D000069604:Dabigatran; D017984:Enoxaparin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D006470:Hemorrhage / Q000139:chemically induced; D007279:Injections, Subcutaneous; D011474:Prosthesis Design; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D013552:Swine; D013916:Thrombelastography; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D011725:Pyridines; D000069604:Dabigatran