Department of Health Policy, The London School of Economics and Political Science, London, UK.
Cardiology Department, Laiko General Hospital, 17 Agiou Thoma Street, 11 527, Athens, Greece.
Heart Fail Rev. 2019 May;24(3):367-377. doi: 10.1007/s10741-018-9758-0.
Heart failure with preserved ejection fraction (HFpEF) is a disease with limited evidence-based treatment options. Mineralocorticoid receptor antagonists (MRA) offer benefit in heart failure with reduced ejection fraction (HFrEF), but their impact in HFpEF remains unclear. We therefore evaluated the effect of MRA on echocardiographic, functional, and systemic parameters in patients with HFpEF by a systematic review and meta-analysis. We searched MEDLINE, EMBASE, clinicaltrials.gov , and Cochrane Clinical Trial Collection to identify randomized controlled trials that (a) compared MRA versus placebo/control in patients with HFpEF and (b) reported echocardiographic, functional, and/or systemic parameters relevant to HFpEF. Studies were excluded if: they enrolled asymptomatic patients; patients with HFrEF; patients after an acute coronary event; compared MRA to another active comparator; or reported a follow-up of less than 6 months. Primary outcomes were changes in echocardiographic parameters. Secondary end-points were changes in functional capacity, quality of life measures, and systemic parameters. Quantitative analysis was performed by generating forest plots and calculating effect sizes by random-effect models. Between-study heterogeneity was assessed through Q and I statistics. Nine trials with 1164 patients were included. MRA significantly decreased E/e' (mean difference - 1.37, 95% confidence interval - 1.72 to - 1.02), E/A (- 0.04, - 0.08 to 0.00), left ventricular end-diastolic diameter (- 0.78 mm, - 1.34 to - 0.22), left atrial volume index (- 1.12 ml/m, - 1.91 to - 0.33), 6-min walk test distance (- 11.56 m, - 21 to - 2.13), systolic (- 4.75 mmHg, - 8.94 to - 0.56) and diastolic blood pressure (- 2.91 mmHg, - 4.15 to - 1.67), and increased levels of serum potassium (0.23 mmol/L, 0.19 to 0.28) when compared with placebo/control. In patients with HFpEF, MRA treatment significantly improves indices of cardiac structure and function, suggesting a decrease in left ventricular filling pressure and reverse cardiac remodeling. MRA increase serum potassium and decrease blood pressure; however, a small decrease in 6-min-walk distance is also noted. Larger prospective studies are warranted to provide definitive answers on the effect of MRA in patients with HFpEF.
射血分数保留的心力衰竭（HFpEF）是一种治疗方法有限的疾病。盐皮质激素受体拮抗剂（MRA）在射血分数降低的心力衰竭（HFrEF）中具有益处，但它们在 HFpEF 中的作用仍不清楚。因此，我们通过系统评价和荟萃分析评估了 MRA 对 HFpEF 患者超声心动图、功能和全身参数的影响。我们在 MEDLINE、EMBASE、clinicaltrials.gov 和 Cochrane 临床试验收藏中搜索了比较 MRA 与安慰剂/对照在 HFpEF 患者中的随机对照试验（a）和（b）报告了与 HFpEF 相关的超声心动图、功能和/或全身参数。如果研究符合以下条件，则将其排除在外：（a）纳入无症状患者；（b）HFrEF 患者；（c）急性冠状动脉事件后患者；（d）将 MRA 与另一种活性对照药物进行比较；或（e）报告随访时间少于 6 个月。主要结局为超声心动图参数的变化。次要终点为功能容量、生活质量测量和全身参数的变化。通过生成森林图和使用随机效应模型计算效应大小来进行定量分析。通过 Q 和 I 统计量评估研究间异质性。纳入了 9 项试验，共 1164 名患者。MRA 显著降低了 E/e'（平均差异-1.37，95%置信区间-1.72 至-1.02）、E/A（-0.04，-0.08 至 0.00）、左心室舒张末期直径（-0.78 毫米，-1.34 至-0.22）、左心房容积指数（-1.12 毫升/米，-1.91 至-0.33）、6 分钟步行测试距离（-11.56 米，-21 至-2.13）、收缩压（-4.75 毫米汞柱，-8.94 至-0.56）和舒张压（-2.91 毫米汞柱，-4.15 至-1.67），与安慰剂/对照相比，血清钾水平升高（0.23 毫摩尔/升，0.19 至 0.28）。在 HFpEF 患者中，MRA 治疗可显著改善心脏结构和功能指标，提示左心室充盈压降低和心脏逆重构。MRA 增加血清钾并降低血压；然而，也注意到 6 分钟步行距离略有下降。需要更大的前瞻性研究来提供关于 MRA 在 HFpEF 患者中作用的明确答案。
