Objective: In the interest of exploring alternatives to warfarin, we tested the hypothesis that clopidogrel combined with aspirin is effective for thromboprophylaxis of mechanical valves using a swine model. Methods: Adult swine underwent heterotopic implantation of a modified bileaflet mechanical valved conduit bypassing the ligated, native descending thoracic aorta. Animals were randomized to no anticoagulation (n = 7), 175 U/kg dalteparin administered subcutaneously twice daily (n = 9), 325 mg of aspirin (n = 6), 75 mg of clopidogrel (n = 6), or 325 mg of aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 30 days. Additionally, 11 animals were randomized to no anticoagulation (n = 5) or 325 mg of oral aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 150 days. Results: At 30 days, we observed 216 ± 270 mg of thrombus for the no anticoagulation group, 53 ± 91 mg for the dalteparin group, 33 ± 23 mg for the aspirin group, 25 ± 10 mg for the clopidogrel group, and 17 ± 9 mg for the combined aspirin and clopidogrel group, respectively (P < .01 for clopidogrel and aspirin vs no anticoagulation). At 150 days, we observed 223 ± 200 mg of thrombus for the no anticoagulation group and 4 ± 4 mg for the aspirin and clopidogrel group (P = .02). Mean platelet deposition on the valve was 4.1 × 109 ± 3.6 × 109 for the no anticoagulation and 6.81 × 107 ± 1.4 × 108 for the combined aspirin and clopidogrel groups, respectively (P = .03). No major hemorrhagic events were observed. Conclusions: Effective short- and long-term thromboprophylaxis of mechanical valves can be achieved by using dual-antiplatelet therapy in this porcine model. Prospective human trials should be conducted with combination aspirin and clopidogrel as an alternative to warfarin in patients with bileaflet mechanical aortic valves.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine