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J Thorac Cardiovasc Surg 2008;136:908-914
© 2008 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves: An in vivo study in swine

^a Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn
^b Clinician Investigator Program, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minn
^c Advanced Cardiology Center, Mayaguez, Puerto Rico

Received for publication December 3, 2007; accepted for publication January 28, 2008.

^_* Address for reprints: Hartzell V. Schaff, MD, Division of Cardiovascular Surgery, Mayo Clinic, 200 First St SW, Rochester, MN 55905. (Email: schaff{at}mayo.edu).

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 x 10⁹ ± 3.6 x 10⁹ for the no anticoagulation and 6.81 x 10⁷ ± 1.4 x 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.