Helmy, Irfan

Objective 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.

BACKGROUND: With evolving therapy for heart failure with reduced ejection fraction, the benefits of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT) remain unclear, particularly for nonischemic cardiomyopathy (NICM). This study evaluates long-term survival among patients with NICM treated with CRT defibrillator (CRT-D) versus CRT pacemaker (CRT-P). METHODS: DECIDE-CRT (Cardiac Resynchronization With or Without Defibrillator in Non-Ischemic Cardiomyopathy) is a multicenter cohort study across 170 US Veterans Affairs hospitals. We identified patients with NICM receiving primary-prevention CRT-P or CRT-D between January 1, 2006, and December 31, 2020. Using a propensity score approach, we applied inverse probability of treatment weighting to balance baseline characteristics between the CRT-P and CRT-D groups. An inverse probability of treatment weighting–weighted Cox model estimated hazards for all-cause mortality. Secondary outcomes included generator replacement, device-related infections, hospitalization for heart failure, and ventricular arrhythmias. RESULTS: Of 16 609 CRT recipients, 3965 met NICM primary-prevention criteria (CRT-D=3158; CRT- P =807). At baseline, patients with NICM receiving CRT-P were much older, with more cardiovascular and noncardiovascular comorbidities compared with the CRT-D group. During the median follow-up of 5.2 years, the mortality rate for CRT-P versus CRT-D was 9.46 versus 9.21 per 100 person-years (RR, 0.97 [95% CI, 0.71–1.13]; P =0.66). The adjusted hazard ratio for all-cause mortality using the inverse probability of treatment weighting-Cox model was 0.90 (95% CI, 0.71–1.13; P =0.34). There was no difference in adjusted hazard for heart failure hospitalization (hazard ratio, 1.27 [95% CI, 0.86–1.87]), while the CRT-D group had higher rates of generator replacement and device-related infections. CONCLUSIONS: This nationwide observational study from the Veterans Affairs Health system did not demonstrate a clear survival advantage with the addition of a defibrillator among patients with NICM receiving CRT although residual confounding cannot be excluded. Given the uncertainty surrounding the incremental benefit of the defibrillator in this setting, a randomized trial is needed to test the incremental value of CRT-D over CRT-P in NICM.