TABLE 2.

The design of the study and main results of the VICTORIA‐HF, ⁷ GALACTIC‐HF ⁸ and AFFIRM‐HF ⁹ trials are summarised

VICTORIA‐HF 7 (n = 5,050)				GALACTIC‐HF 8 (n = 8,256)			AFFIRM‐HF 9 (n = 1,108)
Vericiguat (2.5‐10 mg once daily) vs. placebo				Omecamtiv mecarbil (25, 37.5 or 50 mg b.i.d.) vs. placebo			Endovenous ferric carboxymaltose vs. placebo
Clinical setting
Outpatients				Inpatients or outpatients			Inpatients
Main inclusion criteria
NYHA classes II–IV				NYHA classes II–IV			Hospitalisation due to acute decompensated heart failure
LVEF ≤45% in the last 12 months				LVEF ≤35%			LVEF <50% Ferritin <100 μg/L, or 100‐299 μg/L with transferrin saturation <20%
BNP	SR AF	≥300 >500		BNP	SR AF	≥125 >375	BNP	SR AF	≥400 >600
NT‐proBNP	SR >1,000 AF >1 600			NT‐proBNP	SR AF	≥400 >1,200	NT‐proBNP	SR AF	≥1,200 >2,400
Optimal treatment, ARNI introduction encouraged				Optimal treatment			At least 40 mg intravenous furosemide or equivalent
Main exclusion criteria
Arterial pressure <100 mm Hg Use of long‐acting nitrates, soluble guanylate cyclase stimulators or phosphodiesterase type 5 inhibitor				Mechanical support or intravenous medication for haemodynamic or clinical instability Systolic arterial pressure <85 mm Hg			Immediate need of transfusion or with Hb <8 g/dL* or with Hb >15 g/dL Renal dialysis
s				eGFR <20 mL/min/1.73 m2
Follow‐up (median)
10.8 months				21.8 months			12 months
Main results
Primary end point: ‐ CV death or first hHF ARR, −3 × 100 patients/year HR, 0.90 (95% CI, 0.82‐0.98); P =.02 Main secondary end points: ‐ Total number HF hospitalisation or urgent visit: HR, 0.91 (95% CI, 0.84‐0.99); P =.02 ‐ hHF: HR, 0.90 (95% CI, 0.81‐1.0); p: NA ‐ CV death: HR, 0.93 (95% CI, 0.81‐1.06); p: NA ‐ All‐cause death: HR, 0.95 (95% CI, 0.84‐1.07); P =.38				Primary end point: ‐ CV death and hHF or urgent HF visit: ARR, −2.1 × 100 patients/year HR, 0.92 (95% CI, 0.86‐0.99); P =.03 Main secondary end points: ‐ hHF: HR, 0.95 (95% CI, 0.87‐1.03); p: NA ‐ CV death: HR, 1.02 (95% CI, 0.92‐1.11); P =.86 ‐ All‐cause death: HR, 1.00 (95% CI, 0.92‐1.09); p: NA			Primary end point: ‐ total number CV death and hHF: ARR, −15.35 × 100 patients/year HR, 0.79 (95% CI, 0.62‐1.01); P =.059 COVID sensitivity analysis ARR, −18.24 × 100 patients/year HR, 0.75 (95% CI, 0.59‐0.96); P =.024 Main secondary end points: ‐ Total number HF hospitalisation: HR, 0.74 (95% CI, 0.58‐0.94); P =.013 COVID sensitivity analysis HR, 0.70 (95% CI, 0.55‐0.90); P =.005
Non‐HF‐related adverse events
Vericiguat vs. placebo: ‐ Symptomatic hypotension 9.1% vs. 7.9% (P =.12) ‐ Syncope 4.0% vs. 3.5% (P =.30) ‐ Anaemia 7.6% vs. 5.7%				Omecamtiv vs. placebo: ‐ Similar major cardiac ischaemic events (4.9% vs. 4.6%) and myocardial infarction (3.0% vs. 2.9%) ‐ Similar rate of ventricular arrhythmic events			Similar rate in ferric carboxymaltose and placebo

Abbreviations: ACEi, ACE inhibitor; AF, atrial fibrillation; ARB, angiotensin II receptor blocker; ARNi, angiotensin receptor neprilysin inhibitor; ARR, absolute risk reduction; CI, confidence interval; eGFR, estimated glomerular filtration rate; hHF, hospitalisation for heart failure; HR, hazard ratio; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonists; NA, not available; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; SR sinus rhythm.