Cardiology Department, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.
Cardiovascular Research and Development Center-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
ESC Heart Fail. 2023 Jun;10(3):1822-1834. doi: 10.1002/ehf2.14284. Epub 2023 Mar 10.
Recent heart failure (HF) guidelines have re-classified HF patients with left ventricular ejection fraction (LVEF) between 41% and 49% as HF with mildly reduced ejection fraction (HFmrEF). HFmrEF treatment is often considered a grey zone as no randomized controlled trials (RCTs) were conducted exclusively on these patients.
A network meta-analysis (NMA) was performed to compare treatment effect of mineralocorticoid receptor antagonists (MRA), angiotensin receptor neprilysin inhibitor (ARNi), angiotensin receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and beta-blockers (BB) in HFmrEF cardiovascular (CV) outcomes.
RCTs sub-analyses evaluating the efficacy of pharmacological treatment in HFmrEF patients were searched. Hazard ratios (HRs) and their variance were extracted from each RCT for (i) composite of CV death or HF hospitalizations, (ii) CV death, and (iii) HF hospitalizations. A random-effects NMA was performed to compare and assess the treatment efficiency. Six RCTs with subgroup analysis according to participants' ejection fraction, a patient-level pooled meta-analysis of two RCTs, and an individual patient-level analysis of eleven BB RCTs were included, totalling 7966 patients. To our primary endpoint, SGLT2i vs. placebo was the only comparison with significant results, with a 19% risk reduction in the composite of CV death or HF hospitalizations [HR 0.81, 95% confidence interval (CI) 0.67-0.98]. In HF hospitalizations, the impact of the pharmacological therapies was more notorious, and ARNi reduced in 40% the risk of HF hospitalizations (HR 0.60, 95% CI 0.39-0.92), SGLT2i in 26% (HR 0.74, 95% CI 0.59-0.93) and renin-angiotensin system inhibition (RASi) with ARB and ACEi in 28% (HR 0.72, 95% CI 0.53-0.98). Although BBs were globally less beneficial, they were the only class that supported a reduced risk of CV death (HR vs. placebo: 0.48, 95% CI 0.24-0.95). We did not observe a statistically significant difference in any comparison between active treatments. There was a sound reduction with ARNi on the primary endpoint (HR vs. BB: 0.81, 95% CI 0.47-1.41; HR vs. MRA 0.94, 95% CI 0.53-1.66) and on HF hospitalizations (HR vs. RASi 0.83, 95% CI 0.62-1.11; HR vs. SGLT2i 0.80, 95% CI 0.50-1.30).
In addition to SGLT2i, pharmacological treatment recommended for HF with reduced LVEF, namely, ARNi, MRA, and BB, can also be effective in HFmrEF. This NMA did not show significant superiority over any pharmacological class.
最近的心力衰竭（HF）指南将左心室射血分数（LVEF）在 41%至 49%之间的 HF 患者重新分类为射血分数轻度降低的心力衰竭（HFmrEF）。HFmrEF 的治疗通常被认为是一个灰色地带，因为没有专门针对这些患者的随机对照试验（RCT）。
进行网络荟萃分析（NMA）比较在 HFmrEF 心血管（CV）结局中，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）、血管紧张素受体阻滞剂（ARB）、血管紧张素转换酶抑制剂（ACEi）、钠-葡萄糖共转运蛋白-2 抑制剂（SGLT2i）和β-受体阻滞剂（BB）的治疗效果。
检索了评估 HFmrEF 患者药物治疗疗效的 RCTs 亚组分析。从每项 RCT 中提取（i）CV 死亡或 HF 住院的复合终点，（ii）CV 死亡，和（iii）HF 住院的风险比（HRs）及其方差。进行了随机效应 NMA 比较和评估治疗效果。共纳入了 6 项根据参与者射血分数进行亚组分析的 RCT、2 项 RCT 的患者水平汇总荟萃分析以及 11 项 BB RCT 的个体患者水平分析，共计 7966 名患者。对于我们的主要终点，SGLT2i 与安慰剂的比较仅有显著结果，SGLT2i 降低了 19%的 CV 死亡或 HF 住院的复合终点风险[HR 0.81，95%置信区间（CI）0.67-0.98]。在 HF 住院方面，药物治疗的影响更为明显，ARNi 降低了 40%的 HF 住院风险[HR 0.60，95%CI 0.39-0.92]，SGLT2i 降低了 26%[HR 0.74，95%CI 0.59-0.93]，肾素-血管紧张素系统抑制（RASi）与 ARB 和 ACEi 降低了 28%[HR 0.72，95%CI 0.53-0.98]。尽管 BB 总体上获益较少，但它们是唯一降低 CV 死亡风险的类别[HR 与安慰剂：0.48，95%CI 0.24-0.95]。我们没有观察到任何活性治疗之间的统计学显著差异。ARNi 在主要终点（HR 与 BB：0.81，95%CI 0.47-1.41；HR 与 MRA：0.94，95%CI 0.53-1.66）和 HF 住院（HR 与 RASi：0.83，95%CI 0.62-1.11；HR 与 SGLT2i：0.80，95%CI 0.50-1.30）方面的疗效明显降低。
除了 SGLT2i 外，推荐用于射血分数降低的 HF 的药物治疗，即 ARNi、MRA 和 BB，也可有效用于 HFmrEF。这项 NMA 并没有显示任何药物类别具有显著优势。
