Clinical effectiveness of sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction: nationwide cohort study (REFINE-HFpEF)
Padmini Selvaganesan, Mohamad Karnib, Irfan Helmy, Yogesh N V Reddy, Mohammed Osman, Jayakumar Sahadevan, Rosita Zakeri, Varun SundaramObjective
To evaluate the clinical effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in reducing the risk of hospital admission for heart failure and mortality in a contemporary nationwide cohort of patients with heart failure with preserved ejection fraction (HFpEF).
Design
Nationwide cohort study (REFINE-HFpEF).
Setting
170 veteran health medical centres across the US, 1 January 2014 to 31 December 2021.
Participants
2177 patients with type 2 diabetes and HFpEF; 1129 patients were newly prescribed SGLT2 inhibitors and 1048 were newly prescribed dipeptidyl peptidase 4 (DPP4) inhibitors or sulfonylureas.
Main outcome measures
The primary outcome was a composite of all cause mortality and hospital admission for heart failure. Secondary outcomes included all cause mortality only and serial changes in body weight. Hazard ratios were derived from Cox proportional hazards models, incorporating inverse probability of treatment weighting based on propensity scores to account for confounding.
Results
From a validated cohort of 179 288 patients with type 2 diabetes and HFpEF, the study included 1129 new users of SGLT2 inhibitors (active treatment) and 1048 new users of DPP4 inhibitors or sulfonylureas (comparators). After a median follow-up of 2.63 years, 46.4% of the study population had at least one hospital admission for heart failure (n=1011) and the overall mortality rate was 45.9% (n=1000). Use of SGLT2 inhibitors was associated with a relative risk reduction in the primary composite outcome of 18% compared with the use of DPP4 inhibitors or sulfonylureas (hazard ratio 0.82, 95% confidence interval 0.70 to 0.96; P=0.01). The adjusted hazard ratio for all cause mortality only was 0.73 (0.60 to 0.89; P=0.002). Weight loss was similar in the two groups.
Conclusions
In this large, contemporary, nationwide cohort of patients with HFpEF, type 2 diabetes, and high event rates, starting SGLT2 inhibitors was associated with a significantly lower risk of hospital admission for heart failure and all cause mortality compared with starting treatment with DPP4 inhibitors or sulfonylureas.