Key result
SGLT2i initiation in older sacubitril-valsartan users with HF is linked to ~29% lower HHF or mortality.
Why the study?
Large-scale real-world evidence regarding the outcomes of SGLT2 inhibitor initiation added to sacubitril-valsartan was limited.
Does SGLT2 inhibitor initiation reduce the composite of hospitalization for heart failure or all-cause mortality in older sacubitril-valsartan users with heart failure?
Cohort (n=10,000)
Does SGLT2 inhibitor initiation reduce the composite of hospitalization for heart failure or all-cause mortality in older sacubitril-valsartan users with heart failure?
In older heart failure patients treated with sacubitril-valsartan, the addition of an SGLT2 inhibitor is associated with a significantly lower risk of heart failure hospitalization or all-cause mortality, with an expected increase in genital infections.
Answers are grounded in this paper and cite their sources.
Supports the real-world benefit of SGLT2 inhibitors in heart failure; extends RCT efficacy to.
BACKGROUND: Large-scale real-world evidence regarding outcomes of sodium-glucose cotransporter-2 inhibitors (SGLT2i) initiation added to sacubitril-valsartan is currently limited. We aim to investigate effectiveness and safety of SGLT2i initiation among older sacubitril-valsartan users with heart failure in routine clinical practice. METHODS: This prevalent new-user cohort study used linkable administrative data in Ontario, Canada, to emulate a target trial. In sacubitril-valsartan users with heart failure aged ≥66 years, SGLT2i initiators were matched on time-conditional propensity scores to non-initiators (October 2019 to June 2024). The primary effectiveness outcome was a composite of hospitalization for heart failure (HHF) or all-cause mortality. We also studied safety outcomes, including acute kidney injury (AKI), genital infection, urinary tract infection (UTI), falls, hospitalization for hypotension, diabetic ketoacidosis (DKA), and hypoglycemia. RESULTS: Among 5,000 matched pairs, SGLT2i initiation was associated with lower HHF or all-cause mortality (hazard ratio [HR] 0.71, 95% confidence interval 0.64-0.78; 1-year absolute risk: 13.9% versus 19.2%). SGLT2i initiation was associated with a higher genital infection risk (2.36, 1.58-3.51; 1.8% versus 0.7%) but not with higher rates of falls, hospitalization for hypotension, or UTI. DKA was uncommon among SGLT2i users with diabetes as were hypoglycemic events among SGLT2i users without diabetes. SGLT2i initiation showed lower AKI among those with diabetes (0.78, 0.66-0.94) but not among those without diabetes (1.01, 0.66-0.94; HR homogeneity: p=0.035). CONCLUSIONS: This observational real-world evidence study supports effectiveness of SGLT2i among older sacubitril-valsartan users with heart failure, and suggests no increase in the safety outcomes studied, except genital infection.
No takes yet. Share an insight, caveat, or question.
Wu et al. (2026) conducted a cohort in Heart failure (n=10,000). SGLT2 inhibitors vs. Non-initiators was evaluated on Composite of hospitalization for heart failure (HHF) or all-cause mortality (HR 0.71, 95% CI 0.64-0.78). SGLT2 inhibitor initiation in older sacubitril-valsartan users with heart failure reduced the risk of heart failure hospitalization or all-cause mortality (HR 0.71; 95% CI 0.64-0.78).
Synapse has enriched 10 related papers. Consider them for comparative context: