Table 1. Studies on the clinical efficacy of vericiguat.

 

HFpEF: heart failure with preserved ejection fraction; KCCQ: Kansas City Cardiomyopathy Questionnaire; HFrEF: heart failure with reduced ejection fraction; CV: cardiovascular; NT-proBNP: N-terminal pro-brain natriuretic peptide; LAV: left atrial volume; SGLT2i: sodium-glucose cotransporter-2 inhibitor; HF: heart failure; eGFR: estimated glomerular filtration rate; WRF: worsening renal function; CVD: cardiovascular death; HFH: heart failure hospitalization

Clinical efficacy of vericiguat
Author [Year]	Groups studied and intervention	Results and findings	Conclusions
Armstrong et al. [74]	789 patients with HFpEF would be randomized to receive either 15 mg, 10 mg of vericiguat, or a placebo for 24 weeks.	Vericiguat therapy did not increase the KCCQ score	Among patients with HFpEF, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ.
Armstrong et al. [66]	5,050 patients with HFrEF were randomly assigned to receive either vericiguat therapy (10mg/d) or placebo therapy.	There was a primary outcome event in 35.5% of the vericiguat group and 38.5% of the placebo group. Hospitalization occurred in 27.4% of the vericiguat group and 29% of the placebo group. 16.4% of the vericiguat group died from CV causes, while 17.5% of the placebo group died.	The incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than among those who received a placebo.
Gheoghiade et al. [76]	456 patients with HFpEF were randomized to receive either 1.25 mg, 5 mg, or 10 mg of vericiguat, or placebo for 12 weeks	NT-proBNP levels were lower with increasing doses of vericiguat. There was also a reduction in the rate of any adverse event from 77.2% in the placebo to 71.4% in the 10 mg vericiguat group	While vericiguat lowered the NT-proBNP levels, this was not significant.
Pieske et al. [77]	477 patients with HFpEF were randomized to receive either 1.25, 2.5mg fixed doses of vericiguat or 5 or 10 mg of titrated doses of vericiguat starting at 2.5 mg for 12 weeks. NT-proBNP and LAV were assessed at the end of 12 weeks.	Vericiguat was well tolerated but did not significantly change NT-proBNP or LAV amongst patients	Vericiguat does not change NT-proBNP or LAV in patients with HFpEF.
Aimo et al. [75]	Meta-analysis of patients with HFrEF enrolled in phase 3 and phase 2 clinical trials for SGLT2i, sacubitril/valsartan, and vericiguat were analyzed.	There is a trend toward decreased risk of CV death or HF hospitalization with SGLT2i compared to sacubitril/valsartan and Vericiguat therapy. SGLT2i exhibited the greatest effect on HF hospitalization as well as a significant benefit over Vericiguat.	SGLT2i therapy is not associated with a significantly lower risk of CV death or HF hospitalization compared to sacubitril/valsartan or vericiguat. The risk of HF hospitalization does not differ significantly between patients on SGLT2i or sacubitril/valsartan, while SGLT2i therapy is superior to vericiguat.
Voors et al [78]	4,956 patients from the VICTORIA trial had serum creatinine measured at baseline and at weeks 16, 32, and 48. During 48 weeks of treatment, the trajectories in eGFR and creatinine with compared between vericiguat and placebo.	During 48 weeks of treatment, the trajectories in eGFR and creatinine were similar between vericiguat and placebo. WRF, defined as an increase ≥0.3 mg/dL in creatinine from baseline to week 16, was observed in portions of both groups, with no significant difference between groups.	The beneficial effects of vericiguat on the primary outcome of cardiovascular death or hospitalization in those with severe HFrEF are not influenced by eGFR.
Ezekowitz et al. [79]	4,805 patients from the VICTORIA trial with measured NT-proBNP at randomization were evaluated for the primary outcome of CVD or HFH and the secondary outcome of either event on vericiguat vs placebo.	A reduction in the primary composite endpoint and its CVD and HFH components was observed in patients on vericiguat compared with subjects on placebo with NT-proBNP levels up to 8000 pg/ml. Entry-level NT-proBNP >8000 pg/ml had no difference in the primary outcome between vericiguat and placebo.	This provides insight into the potential benefit of vericiguat in high-risk patients with HFrEF, helping identify a patient cohort in whom the medication might be beneficial.