Potential Contribution of Pleiotropic Effects of Direct Anticoagulants to Clinical Benefits


  • David J. Schneider

    Corresponding author
    1. Cardiology Unit, Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, Vermont, USA
    • Correspondence to: David J. Schneider, University of Vermont, 208 South Park Drive, Colchester, VT 05446, USA.

      E-mail: david.schneider@uvm.edu

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Clinical Development Phases I-III Regulatory, Quality, Manufacturing

Two recent large clinical trials that enrolled exclusively or predominantly patients with ST elevation myocardial infarction and tested direct acting anticoagulants (bivalirudin, rivaroxaban) demonstrated a reduction in mortality. While the anticoagulant properties of these agents likely contributed to the beneficial effects, this Commentary will focus on the nonanticoagulant effects and will consider the premise that pleiotropic effects may have contributed to the observed benefit. In these trials, hearts experienced ischemia/reperfusion and the myocardium was directly exposed to activated coagulation factors. Activation of proteinase-activated receptors (PARs) by thrombin and factor Xa would be predicted to increase inflammation and promote ventricular dilatation and fibrosis. Because direct acting anticoagulants effectively inhibit both free and clot-bound coagulation factors, the extent of exposure to activated coagulation factors would be expected to be reduced. The anticipated preservation of left ventricular function should contribute to a reduction in the subsequent risk of death.