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

Stephen H. McKellar, Jess L. Thompson, Raul F. Garcia-Rinaldi, Ryan J. MacDonald, Thoralf M. Sundt, Hartzell V Schaff

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)908-914
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume136
Issue number4
DOIs
StatePublished - Oct 2008

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clopidogrel
Heart Valves
Aspirin
Swine
Dalteparin
Warfarin
Thoracic Aorta
Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves : An in vivo study in swine. / McKellar, Stephen H.; Thompson, Jess L.; Garcia-Rinaldi, Raul F.; MacDonald, Ryan J.; Sundt, Thoralf M.; Schaff, Hartzell V.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 136, No. 4, 10.2008, p. 908-914.

Research output: Contribution to journalArticle

McKellar, Stephen H. ; Thompson, Jess L. ; Garcia-Rinaldi, Raul F. ; MacDonald, Ryan J. ; Sundt, Thoralf M. ; Schaff, Hartzell V. / Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves : An in vivo study in swine. In: Journal of Thoracic and Cardiovascular Surgery. 2008 ; Vol. 136, No. 4. pp. 908-914.
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abstract = "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.",
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T1 - Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves

T2 - An in vivo study in swine

AU - McKellar, Stephen H.

AU - Thompson, Jess L.

AU - Garcia-Rinaldi, Raul F.

AU - MacDonald, Ryan J.

AU - Sundt, Thoralf M.

AU - Schaff, Hartzell V

PY - 2008/10

Y1 - 2008/10

N2 - 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.

AB - 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.

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