Therapeutics and Clinical Risk Management (Mar 2022)
Vericiguat in Heart Failure with a Reduced Ejection Fraction: Patient Selection and Special Considerations
Abstract
Hayah Kassis-George,1 Nathan J Verlinden,1 Sheng Fu,2 Manreet Kanwar1 1Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA, USA; 2Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USACorrespondence: Nathan J Verlinden, Cardiovascular Institute, Allegheny General Hospital, 320 E. North Ave., Pittsburgh, PA, 15212, Tel +1 412-359-3240, Fax +1 412-359-4806, Email [email protected]: With improvement in the understanding of the pathophysiological mechanisms of heart failure with reduced ejection fraction (HFrEF), several drug classes have been developed targeting the renin–angiotensin–aldosterone system, the beta adrenergic system, and to a certain extent the nitric oxide pathway. Recently, the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors has resulted in a reduction in heart failure hospitalizations and cardiovascular death. As a result, SGLT-2 inhibitors are now the fourth drug class recommended as part of guideline-directed medical therapy (GDMT) for HFrEF. Soluble guanylate cyclase (sGC) stimulators, such as vericiguat, are a novel therapy targeting the cyclic guanosine monophosphate (cGMP) pathway with downstream effects including smooth muscle cell relaxation and a reduction in hypertrophy, inflammation, and fibrosis. The recently published VICTORIA trial has demonstrated a reduction in heart failure hospitalizations or cardiovascular death with vericiguat. Patients with a baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) values < 8000 pg/mL may identify a sub-group most likely to benefit with addition of vericiguat. The cumulative benefit of quadruple therapy with the addition of sGC stimulators remains unknown. We review the mechanism of action for sGC stimulators, clinical trial data, and their real-world application to HFrEF patients with consideration of quintuple therapy.Keywords: vericiguat, soluble guanylate cyclase stimulators, heart failure with reduced ejection fraction, guideline-directed medical therapy, VICTORIA
