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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


KangYu Chen

Zhiqiang Nie

Rui Shi

Qi Wang

Fang Shao

Guohong Wu

Zhenqiang Wu

Tao Chen

Chao Li



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
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


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