Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure

Chen, KangYu; Nie, Zhiqiang; Shi, Rui; Yu, Dahai; Wang, Qi; Shao, Fang; Wu, Guohong; Wu, Zhenqiang; Chen, Tao; Li, Chao

Abstract

IMPORTANCE Emerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population. OBJECTIVES To estimate the time to benefit from SGLT2 inhibitors among patients with HF. DESIGN, SETTING, AND PARTICIPANTS This comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022. INTERVENTION Addition of SGLT2 inhibitors or placebo to guideline-recommended therapy. MAIN OUTCOMES AND MEASURES The primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials. RESULTS Five trials consisting of 21 947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (P < .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction. CONCLUSIONS AND RELEVANCE In this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.

• Journal Article Type: Article
• Acceptance Date: Jul 17, 2023
• Online Publication Date: Aug 1, 2023
• Publication Date: Aug 24, 2023
• Deposit Date: Aug 31, 2023
• Publicly Available Date: Aug 31, 2023
• Journal: JAMA Network Open
• Print ISSN: 2574-3805
• Publisher: American Medical Association
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 8
• Article Number: e2330754
• DOI: https://doi.org/10.1001/jamanetworkopen.2023.30754
• Keywords: Aged, Diabetes Mellitus, Type 2 - complications - drug therapy, Humans, Female, Sodium-Glucose Transporter 2 Inhibitors - therapeutic use, Glucose, Heart Failure - drug therapy, Randomized Controlled Trials as Topic, Male, Sodium