TY - JOUR
T1 - Is thrombosis a contributor to heart failure pathophysiology? Possible mechanisms, therapeutic opportunities, and clinical investigation challenges
AU - Zannad, Faiez
AU - Stough, Wendy Gattis
AU - Regnault, Véronique
AU - Gheorghiade, Mihai
AU - Deliargyris, Efthymios
AU - Gibson, C. Michael
AU - Agewall, Stefan
AU - Berkowitz, Scott D.
AU - Burton, Paul
AU - Calvo, Gonzalo
AU - Goldstein, Sidney
AU - Verheugt, Freek W.A.
AU - Koglin, Joerg
AU - O'Connor, Christopher M.
N1 - Funding Information:
Freek W. A. Verheugt: Educational and research grants from Bayer Healthcare, Roche, Eli Lilly, and Boehringer Ingelheim; Consulting honoraria from Daiichi-Sankyo, Eli Lilly, Merck, The Medicines Company, and Bayer Healthcare.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/9/1
Y1 - 2013/9/1
N2 - 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.
AB - 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.
KW - Clinical trial
KW - Heart failure
KW - Research design
KW - Thrombosis
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U2 - 10.1016/j.ijcard.2012.12.018
DO - 10.1016/j.ijcard.2012.12.018
M3 - Review article
C2 - 23298559
AN - SCOPUS:84883283345
VL - 167
SP - 1772
EP - 1782
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
IS - 5
ER -