Dapagliflozin Improves Heart Failure Symptoms and Physical Limitations Across the Full Range of Ejection Fraction: Pooled Patient-Level Analysis From DEFINE-HF and PRESERVED-HF Trials.
Dapagliflozin Improves Heart Failure Symptoms and Physical Limitations Across the Full Range of Ejection Fraction: Pooled Patient-Level Analysis From DEFINE-HF and PRESERVED-HF Trials.
复制标题
达格列净在所有射血分数范围内均可改善心力衰竭症状和身体受限情况：来自DEFINE - HF和PRESERVED - HF试验的汇总患者水平分析
DOI：
10.1161/circheartfailure.122.009837
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发表时间：
2023-07
影响因子：
9.7
通讯作者：
Kosiborod, Mikhail N.
中科院分区：
文献类型：
--
作者：
Nassif, Michael E.;Windsor, Sheryl L.;Gosch, Kensey;Borlaug, Barry A.;Husain, Mansoor;Inzucchi, Silvio E.;Kitzman, Dalane W.;McGuire, Darren K.;Pitt, Bertram;Scirica, Benjamin M.;Shah, Sanjiv J.;Umpierrez, Guillermo;Austin, Bethany A.;Lamba, Sumant;Khumri, Taiyeb;Sharma, Kavita;Kosiborod, Mikhail N.
关键词：
无论射血分数（EF）如何，心力衰竭（HF）患者的症状和身体限制负担都很高。SGLT 2（钠-葡萄糖协同转运蛋白-2）抑制剂对这些结局的获益是否在整个EF范围内存在差异仍不清楚。从DEFINE-HF试验中汇总患者水平数据（达格列净对射血分数降低的心力衰竭患者的生物标志物、症状和功能状态的影响）和PRESERVED-HF试验（达格列净对生物标志物的影响，射血分数保留性心力衰竭患者的症状和功能状态）。这两项研究均为达格列净与安慰剂的随机、双盲、为期12周的试验，招募了纽约心脏协会II级或更高级别和利钠肽升高的参与者。使用ANCOVA检验达格列净对12周时堪萨斯城心肌病问卷（KCCQ）临床总结评分（CSS）变化的影响，该ANCOVA校正了性别、基线KCCQ、EF、房颤、估计肾小球滤过率和2型糖尿病。使用EF和限制性三次样条分类和连续评估达格列净对KCCQ-CSS的影响与EF的相互作用。使用逻辑回归进行应答者分析，检查KCCQ-CSS恶化和有临床意义改善的患者比例。在587例随机化患者中（达格列净组293例，安慰剂组294例），EF ≤40、>40-≤60和>60%分别为262例（45%）、199例（34%）和126例（21%）。达格列净在12周时改善了KCCQ-CSS（安慰剂校正差异5.0分[95%CI，2.6-7.5]; P<0.001）。这在EF≤40（4.6分[95% CI，1.0-8.1]; P=0.01）、>40至≤60（4.9分[95% CI，0.8-9.0]; P=0.02）和>60%（6.8分[95% CI，1.5-12.1]; P=0.01; P相互作用=0.79）的参与者中是一致的。当连续分析EF时，达格列净对KCCQ-CSS的获益也是一致的（P相互作用=0.94）。在应答者分析中，与安慰剂组相比，达格列净组患者病情恶化较少，KCCQ-CSS改善较小、中等和较大的患者较多;无论EF如何，这些结果也是一致的（所有P相互作用值均不显著）。在HF患者中，达格列净治疗12周后显著改善症状和身体限制，在整个EF范围内具有一致且具有临床意义的获益。URL：https://www.clinicaltrials.gov;唯一标识符：NCT 02653482和NCT 03030235。
Patients with heart failure (HF) have a high burden of symptoms and physical limitations, regardless of ejection fraction (EF). Whether the benefits of SGLT2 (sodium-glucose cotransporter-2) inhibitors on these outcomes vary across the full range of EF remains unclear. Patient-level data were pooled from the DEFINE-HF trial (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction) of 263 participants with reduced EF (≤40%), and PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure) of 324 participants with preserved EF (≥45%). Both were randomized, double-blind 12-week trials of dapagliflozin versus placebo, recruiting participants with New York Heart Association class II or higher and elevated natriuretic peptides. The effect of dapagliflozin on the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at 12 weeks was tested with ANCOVA adjusted for sex, baseline KCCQ, EF, atrial fibrillation, estimated glomerular filtration rate, and type 2 diabetes. Interaction of dapagliflozin effects on KCCQ-CSS by EF was assessed using EF both categorically and continuously with restricted cubic spline. Responder analyses, examining proportions of patients with deterioration, and clinically meaningful improvements in KCCQ-CSS were conducted using logistic regression. Of 587 patients randomized (293 dapagliflozin, 294 placebo), EF was ≤40, >40-≤60, and >60% in 262 (45%), 199 (34%), and 126 (21%), respectively. Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference 5.0 points [95% CI, 2.6–7.5]; P<0.001). This was consistent in participants with EF≤40 (4.6 points [95% CI, 1.0–8.1]; P=0.01), >40 to ≤60 (4.9 points [95% CI, 0.8–9.0]; P=0.02) and >60% (6.8 points [95% CI, 1.5–12.1]; P=0.01; Pinteraction=0.79). Benefits of dapagliflozin on KCCQ-CSS were also consistent when analyzing EF continuously (Pinteraction=0.94). In responder analyses, fewer dapagliflozin-treated patients had deterioration and more had small, moderate, and large KCCQ-CSS improvements versus placebo; these results were also consistent regardless of EF (all Pinteractionvalues nonsignificant). In patients with HF, dapagliflozin significantly improves symptoms and physical limitations after 12 weeks of treatment, with consistent and clinically meaningful benefits across the full range of EF. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02653482 and NCT03030235.