Meta-analysis finds SGLT2 inhibitors reduce mortality and hospitalization in older heart failure patients

This systematic review and meta-analysis examined the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in older adults with heart failure. The analysis pooled data from 10 studies—4 randomized controlled trials and 6 observational cohort studies—involving a total of 20,844 patients aged 65 years or older with heart failure. The specific clinical setting was not reported, nor were the exact SGLT2 inhibitor drugs used across the included studies. The population was specifically defined as older adults with heart failure, though the specific heart failure phenotypes (reduced or preserved ejection fraction) were not detailed in the available data.

The intervention was treatment with SGLT2 inhibitors, with the comparator being control (placebo or standard care without SGLT2 inhibitors). Dosing protocols and specific treatment durations were not reported in the meta-analysis summary. The follow-up period for the included studies was also not specified. The analysis did not report a primary outcome, instead presenting multiple key efficacy and safety endpoints.

For efficacy outcomes, the meta-analysis found statistically significant reductions across multiple endpoints. All-cause mortality showed a hazard ratio of 0.81 (95% CI 0.72-0.90; p < 0.001), indicating a 19% relative reduction in risk. Cardiovascular death was reduced with a hazard ratio of 0.83 (95% CI 0.74-0.94; p = 0.004). Hospitalization outcomes showed particularly strong effects: first heart failure hospitalization had a hazard ratio of 0.73 (95% CI 0.66-0.80; p < 0.001), the composite of cardiovascular death or heart failure hospitalization showed a hazard ratio of 0.78 (95% CI 0.70-0.87; p < 0.001), and rehospitalization demonstrated the largest effect size with a hazard ratio of 0.60 (95% CI 0.53-0.69; p < 0.001). Absolute event rates were not reported for any of these outcomes.

Key secondary outcomes included renal function, which showed a mean difference of 1.86 mL/min/1.73 m² per year in estimated glomerular filtration rate preservation favoring SGLT2 inhibitors (95% CI 1.15-2.58; p < 0.001). This suggests a modest but statistically significant slowing of renal function decline in this older heart failure population treated with SGLT2 inhibitors.

Safety findings showed a reduction in serious adverse events with a relative risk of 0.92 (95% CI 0.89-0.95; p < 0.001). Specific adverse event rates for genital infections, urinary tract infections, discontinuations, and overall tolerability were not reported. The reduction in serious adverse events suggests that in this older population, the benefits of SGLT2 inhibitors were not offset by increased serious harm, though the absence of specific infection rates limits complete safety assessment.

These results align with and extend findings from landmark SGLT2 inhibitor trials in heart failure populations. While previous trials like DAPA-HF and EMPEROR-Reduced demonstrated benefits in broader heart failure populations, this meta-analysis specifically focuses on older adults (≥65 years), a subgroup often underrepresented in clinical trials. The magnitude of benefit for hospitalization reduction (HR 0.73 for first HF hospitalization) is consistent with prior trial data, while the mortality benefit (HR 0.81) appears somewhat stronger than some individual trial estimates, possibly due to the inclusion of observational data.

Methodological limitations include the inclusion of observational cohort studies alongside randomized trials, which introduces potential confounding and bias. The specific SGLT2 inhibitor drugs used across studies were not reported, preventing assessment of class effects versus drug-specific effects. Absolute event rates were not provided, limiting clinical interpretation of the absolute risk reduction. The heart failure phenotype (HFrEF vs. HFpEF) was not specified, though recent trials suggest SGLT2 inhibitors benefit both. Funding sources and conflicts of interest were not reported.

Clinical implications suggest that SGLT2 inhibitors should be considered as an important therapeutic option for older adults with heart failure, given the consistent reductions in mortality, hospitalization, and renal function decline observed across multiple studies. The benefits appear to extend to patients aged 65 and older, who represent a substantial portion of clinical practice. However, clinicians should recognize that these findings represent associations rather than proven causation due to the inclusion of observational data.

Unanswered questions include whether benefits differ by specific SGLT2 inhibitor agent, by heart failure phenotype (HFrEF vs. HFpEF), or by age subgroups within the older population (65-74 vs. 75-84 vs. 85+). The safety profile regarding specific adverse events like genital infections in older adults requires further characterization. Long-term effects beyond the study periods included in this meta-analysis remain unknown. Additionally, how SGLT2 inhibitors compare to other heart failure therapies specifically in older adults requires further study.