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 12 251 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 21 947 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.

Funding

None.

中文翻译：

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心力衰竭患者的 SGLT-2 抑制剂：五项随机对照试验的综合荟萃分析

背景

指南中强烈推荐 SGLT2 抑制剂治疗射血分数降低的心力衰竭患者，但其在射血分数较高时的临床获益尚不明确。DELIVER 和 EMPEROR-Preserved 这两项针对射血分数轻度降低或保留的心力衰竭的大规模试验已经完成，与早期射血分数降低试验相结合，可以检验对心血管死亡率和患者亚组的治疗效果。

方法

我们对 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的患者（DAPA-HF 和 EMPEROR-Reduced）和因心力衰竭恶化而入院的试验，无论射血分数如何（SOLOIST） -WHF）。使用具有统一终点定义的试验级数据，我们进行了固定效应荟萃分析，以评估 SGLT2 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因心力衰竭住院的复合。我们评估了感兴趣亚组的主要终点治疗效果的异质性。本研究已在 PROSPERO 注册，CRD42022327527。

发现

在来自 DELIVER 和 EMPEROR-Preserved 的 12 251 名参与者中，SGLT2 抑制剂减少了复合心血管死亡或因心力衰竭首次住院（风险比 0·80 [95% CI 0·73–0·87]），并且两个组成部分的持续减少：心血管死亡 (0·88 [0·77–1·00]) 和首次因心力衰竭住院 (0·74 [0·67–0·83])。在涉及 21 947 名参与者的五项试验的更广泛背景下，SGLT2 抑制剂降低了复合心血管死亡或因心力衰竭住院的风险 (0·77 [0·72–0·82])、心血管死亡 (0·87 [0 ·79–0·95]）、因心力衰竭首次住院（0·72 [0·67–0·78]）和全因死亡率（0·92 [0·86–0·99]）。在射血分数轻度降低或保留的心力衰竭试验以及所有五项试验中，始终观察到每个研究终点的这些治疗效果。对主要终点的治疗效果在检查的 14 个亚组中基本一致，包括射血分数。

解释

SGLT2 抑制剂降低了范围广泛的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疗法的作用，无论射血分数或护理环境如何。

资金

没有任何。