Background

Three drug classes (mineralocorticoid receptor antagonists [MRAs], angiotensin receptor–neprilysin inhibitors [ARNIs], and sodium/glucose cotransporter 2 [SGLT2] inhibitors) reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF) beyond conventional therapy consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and β blockers. Each class was previously studied with different background therapies and the expected treatment benefits with their combined use are not known. Here, we used data from three previously reported randomised controlled trials to estimate lifetime gains in event-free survival and overall survival with comprehensive therapy versus conventional therapy in patients with chronic HFrEF.

Methods

In this cross-trial analysis, we estimated treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, β blocker, MRA, and SGLT2 inhibitor) versus conventional therapy (ACE inhibitor or ARB and β blocker) in patients with chronic HFrEF by making indirect comparisons of three pivotal trials, EMPHASIS-HF (n=2737), PARADIGM-HF (n=8399), and DAPA-HF (n=4744). Our primary endpoint was a composite of cardiovascular death or first hospital admission for heart failure; we also assessed these endpoints individually and assessed all-cause mortality. Assuming these relative treatment effects are consistent over time, we then projected incremental long-term gains in event-free survival and overall survival with comprehensive disease-modifying therapy in the control group of the EMPHASIS-HF trial (ACE inhibitor or ARB and β blocker).

Findings

The hazard ratio (HR) for the imputed aggregate treatment effects of comprehensive disease-modifying therapy versus conventional therapy on the primary endpoint of cardiovascular death or hospital admission for heart failure was 0·38 (95% CI 0·30–0·47). HRs were also favourable for cardiovascular death alone (HR 0·50 [95% CI 0·37–0·67]), hospital admission for heart failure alone (0·32 [0·24–0·43]), and all-cause mortality (0·53 [0·40–0·70]). Treatment with comprehensive disease-modifying pharmacological therapy was estimated to afford 2·7 additional years (for an 80-year-old) to 8·3 additional years (for a 55-year-old) free from cardiovascular death or first hospital admission for heart failure and 1·4 additional years (for an 80-year-old) to 6·3 additional years (for a 55-year-old) of survival compared with conventional therapy.

Interpretation

Among patients with HFrEF, the anticipated aggregate treatment effects of early comprehensive disease-modifying pharmacological therapy are substantial and support the combination use of an ARNI, β blocker, MRA, and SGLT2 inhibitor as a new therapeutic standard.

Funding

None.

中文翻译：

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估计射血分数降低的心力衰竭患者综合疾病缓解药物治疗的终生获益：三项随机对照试验的比较分析。

背景

三种药物（盐皮质激素受体拮抗剂 [MRA]、血管紧张素受体-脑啡肽酶抑制剂 [ARNI] 和钠/葡萄糖协同转运蛋白 2 [SGLT2] 抑制剂）可降低射血分数降低的心力衰竭 (HFrEF) 患者的死亡率，而传统疗法包括：血管紧张素转换酶（ACE）抑制剂或血管紧张素受体阻滞剂（ARB）和β受体阻滞剂。每个类别之前都使用不同的背景疗法进行了研究，并且其联合使用的预期治疗效果尚不清楚。在这里，我们使用之前报道的三项随机对照试验的数据来估计慢性 HFrEF 患者综合治疗与常规治疗相比无事件生存期和总生存期的终生增益。

方法

在这项交叉试验分析中，我们通过间接评估慢性 HFrEF 患者的综合疾病缓解药物治疗（ARNI、β 受体阻滞剂、MRA 和 SGLT2 抑制剂）与常规治疗（ACE 抑制剂或 ARB 和 β 受体阻滞剂）的治疗效果。三个关键试验 EMPHASIS-HF (n=2737)、PARADIGM-HF (n=8399) 和 DAPA-HF (n=4744) 的比较。我们的主要终点是心血管死亡或因心力衰竭首次入院的复合终点；我们还单独评估了这些终点并评估了全因死亡率。假设这些相对治疗效果随着时间的推移是一致的，然后我们预计 EMPHASIS-HF 试验对照组中的综合疾病缓解治疗（ACE 抑制剂或 ARB 和 β 受体阻滞剂）将在无事件生存期和总生存期方面取得长期增量增长）。

发现

综合疾病缓解治疗与传统治疗对心血管死亡或因心力衰竭入院这一主要终点的估算总体治疗效果的风险比 (HR) 为 0·38 (95% CI 0·30–0·47) 。HR 也有利于仅心血管死亡（HR 0·50 [95% CI 0·37–0·67]）、仅因心力衰竭入院（0·32 [0·24–0·43]）以及所有- 导致死亡率（0·53 [0·40–0·70]）。据估计，采用综合缓解病情的药物治疗可以使患者不再因心血管死亡或首次入院而延长 2·7 年（对于 80 岁）至 8·3 年（对于 55 岁）。与传统治疗相比，心力衰竭的发生率增加了 1·4 年（80 岁）至 6·3 年（55 岁）。

解释

在 HFrEF 患者中，早期综合缓解病情药物治疗的预期总体治疗效果是显着的，支持 ARNI、β 受体阻滞剂、MRA 和 SGLT2 抑制剂的联合使用作为新的治疗标准。

资金

没有任何。