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

Faiez Zannad*, Wendy Gattis Stough, Véronique Regnault, Mihai Gheorghiade, Efthymios Deliargyris, C. Michael Gibson, Stefan Agewall, Scott D. Berkowitz, Paul Burton, Gonzalo Calvo, Sidney Goldstein, Freek W.A. Verheugt, Joerg Koglin, Christopher M. O'Connor

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1772-1782
Number of pages11
JournalInternational Journal of Cardiology
Volume167
Issue number5
DOIs
StatePublished - Sep 1 2013

Keywords

  • Clinical trial
  • Heart failure
  • Research design
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Is thrombosis a contributor to heart failure pathophysiology? Possible mechanisms, therapeutic opportunities, and clinical investigation challenges'. Together they form a unique fingerprint.

Cite this