Partial adenosine A1 receptor agonism: a potential new therapeutic strategy for heart failure.
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.
Duke Scholars
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Stroke Volume
- Receptor, Adenosine A1
- Humans
- Heart Failure
- Drug Partial Agonism
- Cardiovascular System & Hematology
- Cardiovascular Agents
- Adenosine A1 Receptor Agonists
- 3201 Cardiovascular medicine and haematology
- 1102 Cardiorespiratory Medicine and Haematology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Stroke Volume
- Receptor, Adenosine A1
- Humans
- Heart Failure
- Drug Partial Agonism
- Cardiovascular System & Hematology
- Cardiovascular Agents
- Adenosine A1 Receptor Agonists
- 3201 Cardiovascular medicine and haematology
- 1102 Cardiorespiratory Medicine and Haematology