SGLT2 Inhibitors Cut Death and Heart Failure Risk Even in Patients Over 80

Heart failure in patients over 80 is a growing clinical challenge, compounded by frailty, malnutrition, low body weight, and multiple comorbidities that frequently exclude this population from landmark randomized controlled trials. While SGLT2 inhibitors like dapagliflozin and empagliflozin have transformed heart failure management in younger and healthier cohorts, their benefit-risk profile in very elderly, frail, or malnourished real-world patients remained poorly characterized. This Japanese single-center retrospective study was designed specifically to fill that gap, examining whether SGLT2 inhibitors remain effective and safe across the full spectrum of octogenarians hospitalized for heart failure.

The study enrolled 1,559 patients over age 80 hospitalized for heart failure at Kokura Memorial Hospital between January 2018 and March 2023, excluding the 179 who died during the index hospitalization. Of these, 233 were prescribed an SGLT2 inhibitor (80.7% initiated during the index admission, 19.3% already on therapy) and 1,326 were not. Baseline differences were notable: the SGLT2i group was younger on average, had better kidney function (higher eGFR), lower clinical frailty scale scores, higher GNRI (geriatric nutritional risk index), better albumin levels, higher LVEF, and higher rates of RAAS inhibitors and mineralocorticoid receptor antagonists. The non-SGLT2i group had higher loop diuretic use, reflecting more advanced congestion and clinical deterioration.

The primary composite outcome — all-cause death or heart failure hospitalization within one year of discharge — occurred in 31.6% of the SGLT2i group versus 47.3% of the non-SGLT2i group (P<0.01). After multivariable Cox regression adjusting for age, sex, CFS, GNRI, eGFR, and quadruple guideline-directed medical therapy use, SGLT2 inhibitors independently reduced all-cause mortality by 42% (adjusted HR 0.58, 95% CI 0.39–0.87, P<0.01) and heart failure rehospitalization by 31% (adjusted HR 0.69, 95% CI 0.52–0.91, P<0.01). These effect sizes are comparable to those observed in the landmark DAPA-HF and EMPEROR-Reduced trials, which enrolled much younger and healthier populations.

The secondary safety composite — hospitalization for ischemic stroke, urinary tract infection, or dehydration — was not significantly increased in the SGLT2i group (adjusted HR 0.80, 95% CI 0.49–1.29, P=0.36). This is particularly reassuring given longstanding clinical concerns about dehydration and infection risk in frail elderly patients on osmotic diuretics. Subgroup analyses across CFS strata (low 1–3, intermediate 4–6, high 7–9), age under versus over 90, BMI quartile, LVEF category, diabetes status, and GNRI quartile showed consistent benefit from SGLT2 inhibitors with no significant interaction terms, meaning high-frailty and low-nutrition patients benefited as much as their healthier counterparts.

The study carries important implications for clinical practice. Physicians often hesitate to initiate SGLT2 inhibitors in octogenarians with low body weight, elevated frailty scores, or poor nutritional status due to fear of worsening sarcopenia or precipitating adverse events. These real-world data provide the most direct evidence yet that such hesitation may be depriving a vulnerable population of meaningful benefit. Caveats include the study's retrospective, single-center, non-randomized design, significant baseline differences between groups suggesting selection bias, and the inability to capture all out-of-hospital events. Nevertheless, the consistency of findings across all subgroups strengthens confidence in the directional conclusion.