Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Am Coll Cardiol. 2023 Nov 7;82(19):1854-1863. doi: 10.1016/j.jacc.2023.08.026. Epub 2023 Aug 25.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are guideline recommended in the management of heart failure (HF). Although these therapies can be initiated even in patients with comorbid chronic kidney disease, some patients may face deterioration of kidney function over time.
In this study, the authors sought to examine the safety and efficacy of continuing SGLT2 inhibitors in HF when the estimated glomerular filtration rate (eGFR) falls below thresholds for initiation.
Associations between a deterioration of eGFR to <25 mL/min/1.73 m, efficacy, and safety outcomes and treatment with dapagliflozin were evaluated in time-updated Cox proportional hazard models in a participant-level pooled analysis of the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials.
Among 11,007 patients, 347 (3.2%) experienced a deterioration of eGFR to <25 mL/min/1.73 m at least once in follow-up. These patients had a higher risk of the primary composite outcome (HR: 1.87; 95% CI: 1.48-2.35; P < 0.001). The risk of the primary outcome was lower with dapagliflozin compared with placebo among patients who did (HR: 0.53; 95% CI: 0.33-0.83) as well as did not (HR: 0.78; 95% CI: 0.72-0.86) experience deterioration of eGFR to <25 mL/min/1.73 m (P = 0.17). The risk of safety outcomes, including drug discontinuation, was higher among patients with deterioration of eGFR to <25 mL/min/1.73 m; however, rates remained similar between treatment groups including among those who remained on study drug.
Patients with deterioration of eGFR to <25 mL/min/1.73 m had elevated risks of cardiovascular outcomes yet appeared to benefit from continuation of dapagliflozin with no excess in safety outcomes between treatment groups. The benefit-to-risk ratio may favor continuation of dapagliflozin treatment in patients with HF experiencing deterioration of kidney function. Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124; and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂是心力衰竭（HF）管理的指南推荐药物。尽管这些疗法甚至可以在合并慢性肾脏病的患者中开始使用，但有些患者的肾功能可能会随时间恶化。
本研究旨在探讨当估算肾小球滤过率（eGFR）下降至启动治疗的阈值以下时，继续使用 SGLT2 抑制剂治疗 HF 的安全性和疗效。
在一项对 DAPA-HF（研究评估达格列净对慢性心力衰竭患者恶化心力衰竭或心血管死亡发生率的影响）和 DELIVER（达格列净评估改善射血分数保留心力衰竭患者生活）试验的参与者水平汇总分析中，通过时间更新的 Cox 比例风险模型评估 eGFR 恶化至<25 mL/min/1.73 m、疗效和安全性结局与达格列净治疗之间的关联。
在 11007 名患者中，347 名（3.2%）在随访期间至少有一次 eGFR 恶化至<25 mL/min/1.73 m。这些患者发生主要复合结局的风险更高（HR：1.87；95%CI：1.48-2.35；P<0.001）。与安慰剂相比，达格列净治疗组在发生（HR：0.53；95%CI：0.33-0.83）和未发生（HR：0.78；95%CI：0.72-0.86）eGFR 恶化至<25 mL/min/1.73 m的患者中，发生主要结局的风险更低（P=0.17）。eGFR 恶化至<25 mL/min/1.73 m的患者发生安全性结局的风险（包括停药）更高；然而，各治疗组之间的发生率相似，包括仍在接受研究药物治疗的患者。
eGFR 恶化至<25 mL/min/1.73 m 的患者发生心血管结局的风险增加，但继续使用达格列净似乎可获益，且两组之间的安全性结局无差异。获益与风险之比可能有利于继续对肾功能恶化的 HF 患者使用达格列净治疗。DAPA-HF 研究[DAPA-HF]；NCT03036124；和 DELIVER 研究[DELIVER]；NCT03619213）。
