Vericiguat in Heart Failure with a Reduced Ejection Fraction: Patient Selection and Special Considerations

Abstract

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.

Vericiguat in Heart Failure: Characteristics, Scientific Evidence and Potential Clinical Applications

“…NO is synthesized from L-arginine by three nitric oxide synthases, among which endothelial nitric oxide synthase (eNOS) plays a major role. NO diffuses rapidly into vessel smooth muscle cells, binds to the heme subunit of sGC and catalyzes the conversion of guanosine triphosphate (GTP) into the second intracellular messenger, cGMP [ 8 ]. CGMP interacts with three types of intracellular proteins: cGMP-dependent protein kinases, cGMP-regulated ion channels and phosphodiesterases (PDEs) [ 9 ].…”

“…The recent phase III randomized, multicenter VICTORIA trial, where high-risk HF patients were treated with vericiguat, showed a considerable reduction in the composite primary endpoint of death from cardiovascular causes or first HFH [ 8 ]. The secondary outcomes were the components of the primary outcome, first and subsequent HFH, a composite of death from any cause or first HFH and death from any cause [ 22 ].…”

Experience in Initiating Vericiguat in an Advanced Heart Failure Program

“…1 In patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure has been significantly reduced in patients on vericiguat therapy. 1–3 Symptomatic hypotension and syncope adverse effects were noted to be higher in patients on vericiguat, although its statistical significance was not established. 2 Although the vericiguat use in patients with HFrEF in clinical trials has been very promising, there are currently no published reports reflecting the experience of health care centers using vericiguat out of clinical trial settings.…”

“…1–3 Symptomatic hypotension and syncope adverse effects were noted to be higher in patients on vericiguat, although its statistical significance was not established. 2 Although the vericiguat use in patients with HFrEF in clinical trials has been very promising, there are currently no published reports reflecting the experience of health care centers using vericiguat out of clinical trial settings. We are now reporting the baseline characteristics of patients with HFrEF, compliance, and titration in our advanced heart failure clinic at the Georgia Heart Institute.…”

“…Ijeoma Ikedum, MD 1 Abdullah Asreb, MD 1 Ugochukwu Egolum, MD 2 Hua Ling, PharmD 3 1 Northeast Georgia Health System, Gainesville, GA;…”