Short and Long-Term Efficacy of Aspirin and Clopidogrel for Thromboprophylaxis of Mechanical Heart Valves; An In Vivo Study in Swine
Stephen H. McKellar1, Jess L. Thompson1, Raul F. Garcia-Rinaldi2, Ryan J. MacDonald1, Thoralf M. Sundt1, Hartzell V. Schaff1; 1Cardiovascular Surgery, Mayo Clinic, Rochester, MN; 2Advanced Cardiology Center, Mayaguez, PR
Comment on this Abstract
Objective: Chronic anticoagulation with warfarin is standard practice for patients with mechanical valves but has significant limitations. In an attempt to find an alternative 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, bileaflet mechanical valve placement consisting of a modified valved conduit which bypasses the ligated native descending thoracic aorta. Animals were sacrificed at either 30 (acute) or 150 (chronic) days. In a blinded study, 34 acute animals were randomized to one of 5 arms: no anticoagulation (AC) (n=7), 175 units/kg dalteparin (warfarin too problematic) subcutaneously twice daily (n=9), 325 mg oral aspirin daily (n=6), 75 mg oral clopidogrel daily (n=6), or 325 mg oral aspirin and 75 mg clopidogrel daily (n=6). In the chronic study, animals were randomized to one of 2 arms: no AC (n=5) or 325 mg oral aspirin and 75 mg clopidogrel daily (n=6). The primary end point was the amount of valve thrombus at sacrifice. The secondary end points included hemorrhagic complications, platelet inhibition assessed by aggregometry (acute study), and platelet deposition on the valve prosthesis (chronic study).
Results: At 30 days, mean valve thrombus was 216±270 mg for no AC, 53±91 mg for dalteparin, 33±23 mg for aspirin, 25±10 mg for clopidogrel, 17±9 mg for aspirin and clopidogrel, respectively (P<0.01 for clopidogrel and aspirin vs. no anticoagulation). No major postoperative hemorrhagic events were observed; but occult bleeding was detected in three animals (dalteparin n=2, aspirin n=1). Platelet aggregation decreased significantly with combination antiplatelet therapy (P=0.03).
At 150 days, mean valve thrombus was 223±200 mg for the no AC group and 4±4 mg for the aspirin and clopidogrel group (P=0.02). Mean platelet deposition on the valve prosthesis was 4.1x109 ± 3.6x109 for the no anticoagulation and 6.81x107 ± 1.4x108 for the combined aspirin and clopidogrel groups, respectively (P=0.03). No major hemorrhagic events were observed.
Conclusion: Effective short and long-term thromboprophylaxis of mechanical valves can be achieved using dual antiplatelet therapy without excessive hemorrhagic complications in this porcine model. Prospective human trials should be conducted using combination aspirin and clopidogrel as an alternative to warfarin in patients with bileaflet mechanical aortic valves.
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