Initial experience with dual antiplatelet thromboprophylaxis using clopidogrel and aspirin in patients with mechanical aortic prostheses

J Heart Valve Dis. 2009 Nov;18(6):617-25; discussion 626.

Abstract

Background and aim of the study: The aortic mechanical prosthesis (AMP) generates shear stress and causes erythrocyte fragmentation with ADP release that leads to platelet activation, the cause of thromboembolism. Thromboprophylaxis with the antiplatelet agents clopidogrel and aspirin (Clop-ASA) should reduce thromboembolic events in patients receiving an AMP.

Methods: Over an eight-year period at the authors' institutions, a total of 135 patients underwent aortic valve replacement (AVR), with or without concomitant thoracic aortic procedures, and received Clop-ASA as thromboprophylaxis. Platelet reactivity was measured using the Verify Now system. Thromboelastography was commenced in August 2006, and patients were followed at six-month intervals, with echocardiography and assessment of platelet reactivity.

Results: The total follow up was 4,776 months (equivalent to 398 patient-years (pt-yr)); the average follow up was 35.4 +/- 25 months. During follow up, 18 patients (13.3%) died, eight from coronary artery disease and three from valve-related causes. Five patients (3.7%; 1.2%/pt-yr) had bleeding complications, but none experienced valve thrombosis. Two patients (1.5%; 0.5%/pt-yr) had a transient ischemic attack (TIA); one of these occurred in a patient who discontinued Clop-ASA, and the other in a responder to Clop-ASA. Seven patients (5.2%; 1.7%/pt-yr) had strokes, one of which occurred at 48.5 months after AVR. Of the remaining six patients who had a stroke, one was a non-responder to clopidogrel and five had stopped taking Clop-ASA. The incidence of strokes before using the Accumetrics and TEG devices was 2.5% per pt-yr, but only 1.0% per pt-yr thereafter.

Conclusion: Thromboprophylaxis in patients with AMP receiving Clop-ASA seems to be effective. Patients had a low incidence of bleeding, TIA and ischemic stroke, and no valve thrombosis. The use of assays to determine platelet reactivity helped to identify those patients who were resistant to clopidogrel, hyporesponders, and poorly compliant patients. Notably, the incidence of strokes after implementing assays to monitor platelet reactivity was reduced. Deaths were due primarily to myocardial infarction, and none of the deaths was anticoagulant-related. Patients receiving Clop-ASA should undergo routine testing of platelet reactivity, and also continue antiplatelet therapy so as to reduce the risk of ischemic stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aortic Valve*
  • Aspirin / pharmacology
  • Aspirin / therapeutic use*
  • Blood Platelets / drug effects
  • Clopidogrel
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Heart Diseases / mortality
  • Heart Diseases / surgery
  • Heart Valve Prosthesis / adverse effects*
  • Heart Valve Prosthesis Implantation
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Puerto Rico / epidemiology
  • Thromboembolism / etiology
  • Thromboembolism / prevention & control*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use
  • United States / epidemiology

Substances

  • Drug Combinations
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin