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

Int J Cardiol. 2013 Sep 1;167(5):1772-82. doi: 10.1016/j.ijcard.2012.12.018. Epub 2013 Jan 6.

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.

Keywords: Clinical trial; Heart failure; Research design; Thrombosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic / methods
  • Coronary Thrombosis / diagnosis
  • Coronary Thrombosis / physiopathology*
  • Coronary Thrombosis / therapy
  • Heart Failure / diagnosis
  • Heart Failure / physiopathology*
  • Heart Failure / therapy
  • Humans
  • Neurotransmitter Agents / blood
  • Treatment Outcome
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / physiopathology*
  • Venous Thromboembolism / therapy

Substances

  • Neurotransmitter Agents