Heterogeneity in cardiorenal protection by Sodium glucose cotransporter 2 inhibitors in heart failure across the ejection fraction strata: Systematic review and meta-analysis

Table 1 Summary of the reviewed trials

Ref.	Ref-post-hoc	Trial	Year	Follow (yr)	N	Participants	Diabetes proportion %	Heart failure proportion (%)	SGLT2i	Primary outcome
[7]	21	EMPA-REG OUTCOME	2015	3.1	7020	T2DM with established CVD; eGFR ≥ 30 mL/min/1.73 m2	7020 (100)	706 (10)	Empagliflozin	CV death+non-fatal MI+non-fatal stroke
[8]	22	CANVAS/CANVAS-R	2017	2.4	10142	T2DM with CVD or multiple RFs for CVD; eGFR ≥ 30 mL/min/1.73 m2	10142 (100)	1461 (14)	Canagliflozin	CV death+non-fatal MI+non-fatal stroke
[9]	23	DECLARE–TIMI58	2019	4.2	17160	T2DM with CVD or multiple RFs for CVD	17160 (100)	1724 (10)	Dapagliflozin	CV death+MI+ischemic stroke
[10]	24	VERTIS-CV	2020	3.5	8246	T2DM with established CVD; eGFR ≥ 30 mL/min/1.73 m2	8246 (100)	1958 (24)	Ertugliflozin	CV death+non-fatal MI+non-fatal stroke
[11]	25	CREDENCE	2019	2.6	4401	T2DM with CVD+albuminuria (uACR 300–5000); eGFR 30–90 mL/min/1.73 m2	4401 (100)	652 (15)	Canagliflozin	ESKD, doubling of serum creatinine/death from renal/CV cause
[12]	26, 27	DAPA-CKD	2020	2.4	4304	CVD + albuminuria +/- T2DM (eGFR 25-75 mL/min/1.73 m2)	2906 (68)	468 (11)	Dapagliflozin	ESKD, sustained ≥ 50% eGFR decline, death from renal or CV cause
[13]	-	SCORED	2020	1.3	10584	T2DM with CVD & RFs for CVD; (GFR) of 30 to 60 mL/min/1.73 m2	10 584 (100)	3283 (31)	Sotagliflozin	CV death and hospitalizations and urgent visits for HF
[14]	28, 29	DAPA-HF	2019	1.5	4744	HF (EF ≤ 40% & NYHA class II–IV) +/- T2DM; eGFR ≥ 30 mL/min/1.73 m2	2139 (45)	4744 (100)	Dapagliflozin	Worsening HF and CV death
[15]	31	EMPEROR-Reduced	2020	1.3	3730	HF (EF ≤ 40% & NYHA class II–IV) +/- T2DM	1856 (50)	3730 (100)	Empagliflozin	Composite of HF hospitalization and CV death
[16]		EMPEROR-Preserved	2021	26.2 months	5988	HF (EF > 40% & NYHA class II–IV) +/- T2DM; eGFR ≥ 20 mL/min/1.73 m2	2938 (49)	5988 (100)	Empagliflozin	Composite of cardiovascular death or hospitalization for HF
[17]	32	SOLOIST-WHF	2020	0.75	1222	T2DM & recent hospitalization for HF; eGFR ≥ 30 mL/min/1.73 m2	1222 (100)	1222 (100)	Sotagliflozin	CV death and hospitalizations and urgent visits for HF
[18]	30	DELIVER	2022	2.3	6263	HF (EF > 40% & NYHA class II–IV) +/- T2DM	3150 (50)	6263 (100)	Dapagliflozin	Hospitalization for HF or an urgent visit for HF or CV death
[19]		EMPA-KIDNEY	2023	2.0	6609	CKD [eGFR > 20 & < 45 OR 45 < eGFR < 90 mL/min/1.73 m2 & (proteinuria)]	3040 (46)	658 (10)	Empagliflozin	eGFR to < 10 OR decrease in eGFR of ≥ 40% OR renal death

CKD: Chronic kidney disease; CV: Cardiovascular; CVD: Cardiovascular disease; EF: Ejection fraction; eGFR: Esetimated glomerular filtration rate; HF: Heart failure; MI: myocardial infarction; NYHA: New York Hear Associations classification of heart failure; RF: Risk factor; T2DM: Type 2 diabetes mellitus; SGLT2i: Sodium glucose cotransporter 2 inhibitors; NYHA: New York Heart Associations.