The efficacy and safety of sodium-glucose cotransporter 2 inhibitors in patients aged over 80 years with heart failure

Abstract

Aims: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) have demonstrated effectiveness in reducing cardiovascular death and heart failure hospitalization (HFH). However, the efficacy and safety of SGLT2 inhibitors in elderly patients with poor general status, such as very low bodyweight or low nutritional status, who are not included in randomized controlled trials, has not yet been examined. In a real-world setting, the introduction of SGLT2 inhibitors to such elderly patients is a very difficult decision to make. We therefore examined the efficacy and safety of these drugs in elderly heart failure patients in a real-world setting.

Methods and results: In Kokura Memorial Hospital, a retrospective study was conducted on 1559 patients over 80 years old hospitalized for HF between 2018 and 2023. Among them, 1326 were included in the non-SGLT2i group and 233 in the SGLT2i group. A multivariate Cox regression model was used to compare the risk of primary composite outcome (all-cause death and HFH) and secondary safety composite outcome (ischaemic stroke, urinary tract infection and dehydration) at 1 year post-discharge between the two groups. The cumulative 1 year incidence of the composite outcome was significantly higher in the non-SGLT2i group (47.3% vs. 31.6%, P < 0.01). SGLT2 inhibitors independently reduced the risk of all-cause death [adjusted hazard ratio (HR): 0.58, 95% confidence interval (CI): 0.39-0.87, P < 0.01] and HFH (adjusted HR: 0.69, 95% CI: 0.52-0.91, P < 0.01), whereas the risk of safety composite events was not increased (adjusted HR: 0.80, 95% CI: 0.49-1.29, P = 0.36). Subgroup analysis showed no significant interactions between age, diabetes, body mass index, left ventricular ejection fraction, clinical frailty scale, geriatric nutritional risk index and SGLT2 inhibitors consistently reduced composite outcomes across all strata. Similarly, SGLT2 inhibitors did not increase safety composite outcomes at any strata.

Conclusions: SGLT2 inhibitors reduce the risk of all-cause death and HFH without increasing adverse events, even in patients over 80 years old. It may be that SGLT2 inhibitors are effective and safe in patients who are basically hesitant to be introduced to SGLT2 inhibitors, such as those with high frailty, low nutritional status or very low bodyweight.

Keywords: all‐cause death; elderly; extremely low bodyweight; frailty; heart failure; sodium‐glucose cotransporter 2 inhibitors.

Figure 1

Study patient flowchart. SGLT2, sodium‐glucose cotransporter 2; SGLT2i, sodium‐glucose cotransporter 2 inhibitor.

Figure 2

Kaplan–Meier curves for (A) composite outcome, (B) all‐cause death and (C) heart failure hospitalization in the non‐SGLT2i and SGLT2i groups. Follow‐up was censored for 1 year. SGLT2, sodium‐glucose cotransporter 2; SGLT2i, sodium‐glucose cotransporter 2 inhibitor.

Figure 3

Kaplan–Meier curves for (A) safety composite outcome, (B) ischaemic stroke, (C) urinary tract infection and (D) dehydration. SGLT2, sodium‐glucose cotransporter 2; SGLT2i, sodium‐glucose cotransporter 2 inhibitor.

Figure 4

Forest plot for the adjusted hazard ratios (HRs) of composite outcomes according to age, diabetes, body mass index (BMI), left ventricular ejection fraction (LVEF), clinical frailty scale (CFS) and geriatric nutritional risk index (GNRI). The adjusted variables included age and gender. The lower quartile of BMI was 18.2 kg/m², and the lower quartile of GNRI was 39.1. CI, confidence interval; SGLT2i, sodium‐glucose cotransporter 2 inhibitor.

Figure 5

Forest plot for the adjusted hazard ratios (HRs) of safety composite outcomes according to age, diabetes, body mass index (BMI), left ventricular ejection fraction (LVEF), clinical frailty scale (CFS) and geriatric nutritional risk index (GNRI). The adjusted variables included age and gender. The lower quartile of BMI was 18.2 kg/m², and the lower quartile of GNRI was 39.1. CI, confidence interval; SGLT2i, sodium‐glucose cotransporter 2 inhibitor.