Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
British Heart Foundation, University of Glasgow, Glasgow, Scotland, United Kingdom.
J Am Coll Cardiol. 2022 Nov 8;80(19):1775-1784. doi: 10.1016/j.jacc.2022.08.745. Epub 2022 Aug 27.
Recent guidelines support consideration of sodium-glucose cotransporter-2 inhibitors in the long-term management of heart failure (HF) with mildly reduced or preserved ejection fraction. Patients and clinicians may be interested in the expected lifetime benefits of sodium-glucose cotransporter-2 inhibitors in this population.
This study aimed to estimate event-free survival gains from long-term use of dapagliflozin in patients with HF with mildly reduced or preserved ejection fraction overall and in clinically relevant subgroups.
In this prespecified analysis of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we applied validated nonparametric age-based methods to extrapolate potential gains in survival free from the primary endpoint (cardiovascular death or worsening HF event) from long-term use of dapagliflozin. Eligible participants had symptomatic HF, left ventricular ejection fraction >40%, elevated natriuretic peptide levels, and structural heart disease. For every year between the ages of 55 and 85 years, we estimated event-free survival using age at randomization rather than time from randomization as the time horizon. Residual lifespan free from a primary endpoint was estimated based on area under the survival curve in each arm.
Among 6,263 participants, mean survival free from the primary endpoint for a 65-year-old participant was 12.1 years (95% CI: 11.0-13.2 years) with dapagliflozin and 9.7 years (95% CI: 8.8-10.7 years) with placebo, representing a 2.3-year (95% CI: 0.9-3.8 years) event-free survival gain (P = 0.002). Treatment gains in survival free from the primary endpoint ranged from 2.0 years (95% CI: -0.6 to 4.6 years) in a 55-year-old to 1.2 years (95% CI: -0.1 to 2.4 years) in a 75-year-old patient. Mean event-free survival was greater with dapagliflozin than with placebo across all 14 subgroups.
Treatment with dapagliflozin is projected to extend event-free survival by up to 2.0 to 2.5 years among middle-aged and older individuals with HF with mildly reduced or preserved ejection fraction. (DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]; NCT03619213).
最近的指南支持在射血分数轻度降低或保留的心衰（HF）的长期管理中考虑钠-葡萄糖共转运蛋白 2 抑制剂。患者和临床医生可能对该人群中长期使用钠-葡萄糖共转运蛋白 2 抑制剂的预期终生获益感兴趣。
本研究旨在评估达格列净在射血分数轻度降低或保留的心衰患者中的长期使用带来的无事件生存获益，总体上和在临床上相关的亚组中。
在 DELIVER（达格列净评估以改善射血分数保留的心力衰竭患者的生活）的这项预先指定的分析中，我们应用了经过验证的基于年龄的非参数方法，从长期使用达格列净中推断出从主要终点（心血管死亡或心衰恶化事件）无事件生存的潜在获益。合格的参与者有症状性 HF、左心室射血分数>40%、升高的利钠肽水平和结构性心脏病。对于 55 至 85 岁之间的每一年，我们使用随机分组时的年龄而不是从随机分组开始的时间作为时间范围来估计无事件生存。根据每个臂的生存曲线下面积估计主要终点的无剩余寿命。
在 6263 名参与者中，65 岁参与者使用达格列净的无主要终点生存时间为 12.1 年（95%CI：11.0-13.2 年），安慰剂组为 9.7 年（95%CI：8.8-10.7 年），代表 2.3 年（95%CI：0.9-3.8 年）的无事件生存获益（P=0.002）。从主要终点无事件生存中获得的治疗获益范围从 55 岁的 2.0 年（95%CI：-0.6 至 4.6 年）到 75 岁的 1.2 年（95%CI：-0.1 至 2.4 年）。在所有 14 个亚组中，达格列净的无事件生存时间均长于安慰剂。
在射血分数轻度降低或保留的心衰的中年和老年患者中，使用达格列净治疗预计可将无事件生存延长 2.0 至 2.5 年。（DELIVER [达格列净评估以改善射血分数保留的心力衰竭患者的生活]；NCT03619213）。
