Table 10.

Clinical studies of sGC stimulator (activator).

Drug	Study Population	Treatment	Primary and Secondary Endpoints	Main Findings and Conclusions
Praliciguat (CAPACITY-HFpEF) [69]	▪HFrEF patients with LVEF > 40%, impaired peak Vo2, and at least 2 conditions associated with NO deficiency (N = 196).	Praliciguat 40 mg OD or placebo for 12 weeks	Primary: ▪Change in peak Vo2. Secondary: ▪Change in 6-min walk test distance and ventilatory efficiency.	▪No significant difference in the change in peak Vo2 from baseline to week 12.
Riociguat (LEPHT) [141]	▪Patients with HF resulting from pulmonary hypertension. ▪LVEF ≤ 40%. ▪mPAP ≥ 25 mm Hg at rest (N = 201).	Riociguat 0.1, 1, or 2 mg TID or placebo for 16 weeks	Primary: ▪Change in mPAP. Secondary: ▪Change in hemodynamic and echocardiography parameters.	▪Primary endpoint (change in mPAP) was not met. ▪Riociguat improved cardiac index, PVR, SVR, and health-related QoL without altering HR and BP.
Vericiguat (SOCRATES-REDUCED trial) [138]	▪Patients with LVEF < 40% and a recent episode of worsening chronic HF (N = 456).	Vericiguat 1.25, 2.5, 5, or 10 mg OD or placebo for 12 weeks	Primary: ▪Change in NT-proBNP levels from baseline to week 12.	▪No significant difference in the change in NT-proBNP levels between groups. ▪Higher vericiguat had a greater reduction of NT-proBNP levels.
Vericiguat (SOCRATES-PRESERVED trial) [139]	▪Patients with symptomatic worsening chronic HF and LVEF ≥ 45% (N = 477).	Vericiguat 1.25–10 mg OD or placebo for 12 weeks	Primary: ▪Change in NT-proBNP levels and left atrial volume (LAV) from baseline to week 12.	▪No significant differences in the changes in NT-proBNP levels and LAV. ▪Vericiguat was associated with improved QoL.
Vericiguat (VITALITY-HFpEF trial) [68]	▪Patients with chronic HFpEF and LVEF ≥ 45% with NYHA II–III, within 6 months of a recent decompensation (N = 789).	Vericiguat up-titrated to 10 or 15 mg OD or placebo for 24 weeks	Primary: ▪Change in KCCQ PLS (range 0–100) at 24 weeks. Secondary: ▪6-min walking distance.	▪Vericiguat did not improve the physical limitation score of the KCCQ.
Vericiguat (VICTORIA trial) [66,140]	▪Patients with chronic HF and LVEF < 45%. ▪NYHA II–IV. ▪Elevated natriuretic peptide levels (N = 5050).	Vericiguat 10 mg OD or placebo	Primary: ▪Composite of death from CV causes or first hospitalization with HF	▪Among patients with high-risk HF, vericiguat reduced the risk of death from CV causes or hospitalization with HF.
			▪Evaluate NT-proBNP relationship with the primary outcome	▪Vericiguat showed a reduction in CV deaths or HF hospitalization in patients with NT-proBNP levels up to 8000 pg/mL.