Soluble Guanylate Cyclase Stimulators: a Novel Treatment Option for Heart Failure Associated with Cardiorenal Syndromes?
Heart failure in the setting of chronic kidney disease (CKD) is an increasingly common scenario and carries a poor prognosis. Clinicians lack tools for primary or secondary heart failure prevention in patients with cardiorenal syndromes. In patients without CKD, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) and statins mitigate cardiovascular risk in large part due to salutary effects on the endothelium. In the setting of CKD, use of these therapies is limited by adverse effects of hyperkalemia in pre-dialysis CKD (ACE-I/ARB), or potential increased risk of stroke in end-stage renal disease (statins). The soluble guanylate cyclase (sGC) stimulators are a novel class of medications that promote endothelial and myocardial function with no known risk of hyperkalemia or stroke. In this review, we discuss the evidence emerging from recent clinical trials of sGC stimulators in pulmonary hypertension and heart failure, the diseased pathways involved in cardiorenal syndromes likely to be restored by sGC stimulators, and several strategies for designing future clinical trials of cardiorenal syndromes that might shorten the timeline for discovery and approval of effective cardiovascular therapies in these high-risk patients.
Division of Nephrology, Department of Medicine, San Francisco VA Medical Center/University of California, San Francisco, 4150 Clement St., Box 111A1, San Francisco, CA, 94121, USA. ruth.dubin@ucsf.edu.
Ruth F
RF
Dubin
Division of Cardiology, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Sanjiv J
SJ
Shah
D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D059347:Cardio-Renal Syndrome / Q000188:drug therapy* / Q000201:enzymology; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004789:Enzyme Activation / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D012307:Risk Factors; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000071756:Soluble Guanylyl Cyclase
Cyclic GMP; Heart failure; Renal disease; Soluble guanylate cyclase; Therapy