Real-world outcomes and safety of low- vs. standard-dose SGLT2 inhibitors in heart failure
Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a cornerstone in heart failure (HF) treatment. Unlike other guideline-directed medical therapies (GDMT), which require dose titration, SGLT2i were studied and approved at a fixed dose (e.g., 10 mg/day dapagliflozin or empagliflozin). However, lower doses are sometimes prescribed in real-world practice due to safety concerns, despite lacking clinical trial validation. These alternative dosing strategies have not been systematically studied, raising uncertainty about their clinical effectiveness and safety.
To evaluate real-world outcomes of low-dose versus standard-dose SGLT2i in HF patients.
A retrospective cohort study using ICES administrative health databases was conducted. We identified HF patients aged ≥65 years in Ontario, Canada, who were newly prescribed either a low dose (5 mg daily) or standard dose (10 mg daily) of empagliflozin or dapagliflozin between June 1, 2016, and December 31, 2022. The primary outcome was all-cause mortality or cardiovascular (CV) hospitalization. Secondary outcomes included CV and HF hospitalizations, mortality, and adverse drug reactions. Propensity score matching (1:1) was used to adjust for confounders. Multivariable Fine-Gray proportional hazards models examined differences in outcomes between groups. Exclusion criteria included type 1 diabetes, long-term care residents, contraindications to SGLT2i, canagliflozin use and non-Ontario residency. Follow-up continued until treatment…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 202,881 participants or records.
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