美国布列根和妇女医院Scott D Solomon团队研究了SGLT-2抑制剂治疗心力衰竭患者对预后的影响。相关论文于2022年8月27日发表在《柳叶刀》杂志上。
SGLT-2抑制剂在指南中被强烈推荐用于治疗射血分数降低的心力衰竭患者，但其在较高射血分数下的临床益处尚不明确。DELIVER和EMPEROR-Preserved是在射血分数轻度降低或保留的心力衰竭患者中进行的两项大规模试验，与早期射血分数降低的试验相结合，提供了检验心血管死亡率和患者亚组疗效的能力。
研究组对DELIVER和EMPEROR Preserved进行了预先指定的荟萃分析，随后纳入了射血分数降低（DAPA-HF和Emperon降低）的患者和因心力衰竭恶化而住院患者的试验（与射血分数无关，SOLOIST-WHF）。
使用具有统一终点定义的试验级数据，研究组进行了一项固定效应荟萃分析，以评估SGLT-2抑制剂对心力衰竭各种临床终点的影响。该荟萃分析的主要终点是从随机化到心血管死亡或心力衰竭住院复合结局发生的时间。研究组评估了不同亚组主要终点治疗效果的异质性。
来自DELIVER和EMPEROR Preserved的12251名参与者中，SGLT-2抑制剂降低了复合心血管死亡或心力衰竭首次住院的风险，风险比为0.80，两种指标均持续降低：心血管死亡风险比为0.88，心力衰竭首次住院治疗风险比为0.74。
在21947名参与者五项试验的更广泛背景下，SGLT-2抑制剂降低了复合心血管死亡或因心力衰竭住院（0.77）、心血管死亡（0.87）、因心力衰竭首次住院（0.72）和全因死亡（0.92）的风险。在射血分数轻度降低或保留的心力衰竭试验和所有五项试验中，每个研究终点的这些治疗效果均观察到一致。包括射血分数在内的14个亚组对主要终点的治疗效果基本一致。
研究结果表明，SGLT-2抑制剂降低了大量心力衰竭患者的心血管死亡和心力衰竭住院风险，支持其作为心力衰竭基础治疗的作用，无论射血分数或护理设置如何。
附：英文原文
Title: SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials
Author: Muthiah Vaduganathan, Kieran F Docherty, Brian L Claggett, Pardeep S Jhund, Rudolf A de Boer, Adrian F Hernandez, Silvio E Inzucchi, Mikhail N Kosiborod, Carolyn S P Lam, Felipe Martinez, Sanjiv J Shah, Akshay S Desai, John J V McMurray, Scott D Solomon
Issue&Volume: 2022-08-27
Abstract:
Background
SGLT2 inhibitors are strongly recommended in guidelines to treat patients with heart failure with reduced ejection fraction, but their clinical benefits at higher ejection fractions are less well established. Two large-scale trials, DELIVER and EMPEROR-Preserved, in heart failure with mildly reduced or preserved ejection fraction have been done, providing power to examine therapeutic effects on cardiovascular mortality and in patient subgroups when combined with the earlier trials in reduced ejection fraction.
Methods
We did a prespecified meta-analysis of DELIVER and EMPEROR-Preserved, and subsequently included trials that enrolled patients with reduced ejection fraction (DAPA-HF and EMPEROR-Reduced) and those admitted to hospital with worsening heart failure, irrespective of ejection fraction (SOLOIST-WHF). Using trial-level data with harmonised endpoint definitions, we did a fixed-effects meta-analysis to estimate the effect of SGLT2 inhibitors on various clinical endpoints in heart failure The primary endpoint for this meta-analysis was time from randomisation to the occurrence of the composite of cardiovascular death or hospitalisation for heart failure. We assessed heterogeneity in treatment effects for the primary endpoint across subgroups of interest. This study is registered with PROSPERO, CRD42022327527.
Findings
Among 12251 participants from DELIVER and EMPEROR-Preserved, SGLT2 inhibitors reduced composite cardiovascular death or first hospitalisation for heart failure (hazard ratio 0·80 [95% CI 0·73–0·87]) with consistent reductions in both components: cardiovascular death (0·88 [0·77–1·00]) and first hospitalisation for heart failure (0·74 [0·67–0·83]). In the broader context of the five trials of 21947 participants, SGLT2 inhibitors reduced the risk of composite cardiovascular death or hospitalisation for heart failure (0·77 [0·72–0·82]), cardiovascular death (0·87 [0·79–0·95]), first hospitalisation for heart failure (0·72 [0·67–0·78]), and all-cause mortality (0·92 [0·86–0·99]). These treatment effects for each of the studied endpoints were consistently observed in both the trials of heart failure with mildly reduced or preserved ejection fraction and across all five trials. Treatment effects on the primary endpoint were generally consistent across the 14 subgroups examined, including ejection fraction.
Interpretation
SGLT2 inhibitors reduced the risk of cardiovascular death and hospitalisations for heart failure in a broad range of patients with heart failure, supporting their role as a foundational therapy for heart failure, irrespective of ejection fraction or care setting.
DOI: 10.1016/S0140-6736(22)01429-5
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01429-5/fulltext
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