Table 1.

Main characteristics of the included studies.

Study	Year	Treatment	n Patients	Age (Years)	Male Sex (%)	EF (%)	Diabetes (%)	NT-proBNP (pg/mL)	Background HF Therapy				Follow-Up
									ACEi/ARB (%)	Beta-Blocker (%)	ARNI (%)	MRA (%)
GALACTIC-HF [9]	2021	Omecamtiv mecarbil vs. Placebo	8232	65	79	27	40	1971	87 *	94	19	78	22 months (median)
COSMIC-HF [22]	2016	Omecamtiv mecarbil vs. Placebo	298	63	82	29	39	1719	93	97	0	61	24 weeks
VICTORIA [8]	2020	Vericiguat vs. Placebo	5050	67	76	29	47	2816	73	93	15	70	11 months (median)
SOCRATES-REDUCED [23]	2015	Vericiguat vs. Placebo	183	68	82	29	49	3076	81	92	0	62	12 weeks
EMPEROR-Reduced [7]	2020	Empagliflozin vs. Placebo	3730	67	76	27	50	1907	70	95	19	71	16 months (median)
EMPERIAL-Reduced [24]	2020	Empagliflozin vs. Placebo	311	70	74	30	60	1489	55	95	37	58	12 weeks
Empire HF [25]	2020	Empagliflozin vs. Placebo	190	64	85	30	17	594	96 *	95	31	66	12 weeks
SUGAR-DM-HF [26]	2021	Empagliflozin vs. Placebo	105	69	73	33	78	466	61	91	34	60	40 weeks
EMPA-TROPISM (ATRU-4) [27]	2021	Empagliflozin vs. Placebo	84	62	64	36	0	NA	42	88	43	33	6 months
DAPA-HF [6]	2019	Dapagliflozin vs. Placebo	4744	66	77	31	42	1437	84	96	11	71	18 months (median)
DECLARE-TIMI 58 (HFrEF subgroup) [20]	2019	Dapagliflozin vs. Placebo	671	63	84	38	100	NA	88	88	NA	30	4.2 years (median)
DEFINE-HF [21]	2019	Dapagliflozin vs. Placebo	263	61	73	26	62	1136	59	97	33	61	12 weeks

* ACEi, ARB, or ARNI. ACEi—angiotensin-converting enzyme inhibitors; ARB—angiotensin receptor blockers; ARNI—angiotensin receptor-neprilysin inhibitor; EF—ejection fraction; HF—heart failure; MRA—mineralocorticoid receptor antagonist; NA—not available; NT-proBNP—N-terminal pro-B-type natriuretic peptide. This graph shows available comparisons between study treatments (with respect to the primary endpoint). The bullet diameter represents the size of the included randomized controlled trials, and line thickness represents the number of trials with direct comparisons. Direct comparisons are represented by continuous lines, while indirect comparisons are represented by dashed lines.