美国哈佛医学院Scott D Solomon团队近日取得一项新进展。他们分析了综合性疾病改良药物疗法治疗射血分数降低型心力衰竭患者的效果。该成果于2020年5月21日发表在《柳叶刀》杂志上。

盐皮质激素受体拮抗剂（MRAs）、血管紧张素受体中性溶血素抑制剂（ARNIs）和钠/葡萄糖共转运蛋白2（SGLT2）抑制剂，这三种药物可降低射血分数降低的心力衰竭（HFrEF）患者的死亡率，且优于常规疗法，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。此前，这三种药物均单独用不同的背景疗法进行过研究，但联合使用的预期治疗效果尚不明确。

在这项交叉试验分析中，研究组通过间接比较三项关键试验EMPHASIS-HF（n=2737）、PARADIGM-HF（n=8399）和DAPA-HF（n=4744），评估了综合性疾病改良药物治疗（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）对慢性HFrEF患者的疗效。

综合性疾病改良治疗与常规治疗相比，关于心血管死亡或心力衰竭入院的累积疗效的风险比为0.38；其中心血管死亡的风险比为0.50，心力衰竭入院为0.32，全因死亡为0.53。采用综合性疾病改良药物治疗，可延长无心血管死亡或心力衰竭首次入院的生存期达2.7年（80岁）至8.3年（55岁）；而常规治疗可延长1.4年（80岁）至6.3年（55岁）。

总之，在HFrEF患者中，早期综合性疾病改良药物治疗的预期总体疗效显著，支持将ARNI、β受体阻滞剂、MRA和SGLT2抑制剂联合使用作为新的治疗标准。

附：英文原文

Title: Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials

Author: Muthiah Vaduganathan, Brian L Claggett, Pardeep S Jhund, Jonathan W Cunningham, Joo Pedro Ferreira, Faiez Zannad, Milton Packer, Gregg C Fonarow, John J V McMurray, Scott D Solomon

Issue&Volume: 2020-05-21

Abstract: 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.

DOI: 10.1016/S0140-6736(20)30748-0

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30748-0/fulltext