Is thrombosis a contributor to heart failure pathophysiology? Possible mechanisms, therapeutic opportunities, and clinical investigation challenges.


Journal Article (Review)

Thrombotic events (coronary thrombosis, venous thromboembolism, intraventricular thrombosis, intracranial and systemic thromboembolism) occur frequently in patients with heart failure. These events may be precipitated by several mechanisms including hypercoagulability through enhancement of procoagulant reactions, impairment of the protein C pathway, protease activated receptor (PAR) activation, adenosine-mediated thrombosis, or neurohormonal activation; stasis secondary to low cardiac output; and endothelial dysfunction from neurohormonal activation or systemic inflammation. Pathophysiologic evidence and analyses of retrospective data support the hypothesis that antithrombotic agents may improve outcomes in patients with heart failure. Warfarin has not been shown to reduce clinical events in patients with heart failure, although several of the completed randomized trials were underpowered, and the most recent was not placebo-controlled. Many unanswered questions remain that justify continued research in this area. This paper examines the conceptual framework, opportunities, and challenges of clinical investigative approaches with the newer anti-thrombotic agents in patients with heart failure. Critical questions are raised with regard to clinical trial designs that warrant consideration as the field progresses.

Full Text

Duke Authors

Cited Authors

  • Zannad, F; Stough, WG; Regnault, V; Gheorghiade, M; Deliargyris, E; Gibson, CM; Agewall, S; Berkowitz, SD; Burton, P; Calvo, G; Goldstein, S; Verheugt, FWA; Koglin, J; O'Connor, CM

Published Date

  • September 1, 2013

Published In

Volume / Issue

  • 167 / 5

Start / End Page

  • 1772 - 1782

PubMed ID

  • 23298559

Pubmed Central ID

  • 23298559

Electronic International Standard Serial Number (EISSN)

  • 1874-1754

Digital Object Identifier (DOI)

  • 10.1016/j.ijcard.2012.12.018


  • eng

Conference Location

  • Netherlands