Sodium glucose cotransporter 2 inhibitors in the management of heart failure: Veni, Vidi, and Vici

Table 2 Landmark trials of sodium glucose cotransporter-2 inhibitors in heart failure

Trial	Year	Number of patients	SGLT-2i used vs placebo	Endpoints		P value
				SGLT-2 arm	Placebo arm
EMPAREG outcomes	2015	7028	Empagliflozin 10 or 25 mg	CV death, non-fatal MI or stroke: 10.5%	CV death, non-fatal MI or stroke: 12.1%	< 0.001
				All-cause mortality: 3.8%	All-cause mortality 5.1%	< 0.01
				HHF: 2.7%	HHF: 4.1%	0.002
DECLARE TIMI 58	2018	17160	Dapagliflozin 10 mg	CV death, MI, stroke: 8.8%	CV death, MI, stroke: 9.4%	0.17
				CV death or HHF: 4.9%	CV death or HHF: 5.8%	0.005
CANVAS	2017	10142	Canagliflozin	Composite of CV death, non-fatal MI or stroke: 26.9%	Composite of CV death, non-fatal MI or stroke: 31.5%	< 0.0001
				CV death or HHF: 16.3%	CV death or HHF: 20.8%
DAPA-HF	2019	4744	Dapagliflozin 10 mg	CV death or WHF: 16.3%	CV death or WHF: 21.2%	0.001
EMPEROR-Reduced	2020	3730	Empagliflozin 10 mg	CV death or HHF: 19.4%	CV death or HHF: 24.7%	< 0.001
EMPEROR-Preserved	2021	5988	Empagliflozin 10 mg	CV death or HHF: 13.8%	CV death or HHF: 17.1%	< 0.001
DELIVER	2022	6263	Dapagliflozin 10 mg	CV death or WHF: 16.4%	CV death or WHF: 19.5%	< 0.001
SOLOIST WHF	2021	1222	Sotagliflozin	CV death, HHF, urgent visit for HF: 51%	CV death, HHF, urgent visit for HF: 76%	0.001
EMPA RESPONSE	2020	80	Empagliflozin 10 mg	Change in VAS dyspnea score, wt. change, change in NT-proBNP, hospital stay length: 10%	Change in VAS dyspnea score, wt. change, change in NT-pro-BNP, hospital stay length: 13%	0.014
EMPULSE	2022	530	Empagliflozin 10 mg	Net clinical benefit: 53.9%	Net clinical benefit: 39.7%	0.0054
				CV death: 4.2%	CV death: 8.3%
				HF events: 10.6%	HF events: 14.7%
				Change in KCCQ-TSS: 4.5	Change in KCCQ-TSS	0.035
				Wt. change: -1.5 Kg	Wt. change	0.014
EMMY	2022	476	Empagliflozin 10 mg	Change in NT-pro-BNP: 15% lower vs placebo		0.026
				LVEF: 1.5% vs placebo		0.029
				E/e’: 6.8% vs placebo		0.015
				LVESV: 7.5 mL vs placebo		0.0003
				LVEDV: 9.7 mL vs placebo		0.0015

CANVAS: Canagliflozin cardiovascular assessment study; CV: Cardiovascular; DAPA: Dapagliflozin and prevention of adverse outcomes; DECLARE TIMI 58: Dapagliflozin effect on cardiovascular events-thrombolysis in myocardial infarction 58; DELIVER: Dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction heart failure; E/e’: Mitral inflow E wave velocity/annular tissue’ wave velocity; EMMY: Empagliflozin in patients with acute myocardial infarction; EMPAREG: Empagliflozin cardiovascular outcome event trial in type 2 diabetes mellitus patients; EMPA-RESPONSE: Effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure; EMPEROR: Empagliflozin outcome trial in patients with chronic heart failure; EMPULSE: Effect on clinical benefit, safety and tolerability of once daily oral empagliflozin 10 mg compared to placebo, initiated in patients hospitalized for acute heart failure who have been stabilized; HF: Heart failure; HHF: Heart failure hospitalization; KCCQ-TSS: Kansa city cardiomyopathy questionnaire total symptom score; LVEDV: Left ventricular end diastolic volume; LVEF: Left ventricular ejection fraction; LVESV: Left ventricular end systolic volume; MI: Myocardial infarction: NT-pro-BNP: N-terminal pro-B-type natriuretic peptide; SGLT-2is: Sodium glucose cotransporter-2 inhibitors; SOLOIST-WHF: Effect of Sotagliflozin on cardiovascular events in patients with type 2 diabetes post worsening heart failure; VAS: Visual analogue scale; WHF: Worsening heart failure; Wt.: Weight.