Partial adenosine A1 receptor agonism: a potential new therapeutic strategy for heart failure.
Journal Article (Journal Article;Review)
Heart failure (HF) represents a global public health and economic problem associated with unacceptable rates of death, hospitalization, and healthcare expenditure. Despite available therapy, HF carries a prognosis comparable to many forms of cancer with a 5-year survival rate of ~50%. The current treatment paradigm for HF with reduced ejection fraction (EF) centers on blocking maladaptive neurohormonal activation and decreasing cardiac workload with therapies that concurrently lower blood pressure and heart rate. Continued development of hemodynamically active medications for stepwise addition to existing therapies carries the risk of limited tolerability and safety. Moreover, this treatment paradigm has thus far failed for HF with preserved EF. Accordingly, development of hemodynamically neutral HF therapies targeting primary cardiac pathologies must be considered. In this context, a partial adenosine A1 receptor (A1R) agonist holds promise as a potentially hemodynamically neutral therapy for HF that could simultaneous improve cardiomyocyte energetics, calcium homeostasis, cardiac structure and function, and long-term clinical outcomes when added to background therapies. In this review, we describe the physiology and pathophysiology of HF as it relates to adenosine agonism, examine the existing body of evidence and biologic rationale for modulation of adenosine A1R activity, and review the current state of drug development of a partial A1R agonist for the treatment of HF.
Full Text
Duke Authors
Cited Authors
- Greene, SJ; Sabbah, HN; Butler, J; Voors, AA; Albrecht-Küpper, BE; Düngen, H-D; Dinh, W; Gheorghiade, M
Published Date
- January 2016
Published In
Volume / Issue
- 21 / 1
Start / End Page
- 95 - 102
PubMed ID
- 26701329
Electronic International Standard Serial Number (EISSN)
- 1573-7322
Digital Object Identifier (DOI)
- 10.1007/s10741-015-9522-7
Language
- eng
Conference Location
- United States