North Worcestershire VTS St Helens and Knowsley Teaching Hospitals NHS Trust Prescot Merseyside United Kingdom.
Institute of Cardiovascular Sciences University of Birmingham United Kingdom.
J Am Heart Assoc. 2020 Sep 15;9(18):e016239. doi: 10.1161/JAHA.119.016239. Epub 2020 Sep 10.
Background Patients with permanent atrial fibrillation have poor outcomes, exercise capacity, and quality of life even on optimal anticoagulation. Based on mechanistic and observational data, we tested whether the mineralocorticoid receptor antagonist spironolactone can improve exercise capacity, E/e' ratio, and quality of life in patients with permanent atrial fibrillation and preserved ejection fraction. Methods and Results The double-masked, placebo-controlled IMPRESS-AF (Improved Exercise Tolerance in Heart Failure With Preserved Ejection Fraction by Spironolactone on Myocardial Fibrosis in Atrial Fibrillation) trial (NCT02673463) randomized 250 stable patients with permanent atrial fibrillation and preserved left ventricular ejection fraction to spironolactone 25 mg daily or placebo. Patients were followed for 2 years. The primary efficacy outcome was peak oxygen consumption on cardiopulmonary exercise testing at 2 years. Secondary end points included 6-minute walk distance, E/e' ratio, quality of life, and hospital admissions. Spironolactone therapy did not improve peak oxygen consumption at 2 years (14.0 mL/min per kg [SD, 5.4]) compared with placebo (14.5 [5.1], adjusted treatment effect, -0.28; 95% CI, -1.27 to 0.71]; =0.58). The findings were consistent across all sensitivity analyses. There were no differences in the 6-minute walking distance (adjusted treatment effect, -8.47 m; -31.9 to 14.9; =0.48), E/e' ratio (adjusted treatment effect, -0.68; -1.52 to 0.17, =0.12), or quality of life (=0.74 for EuroQol-5 Dimensions, 5-level version quality of life questionnaire and =0.84 for Minnesota Living with Heart Failure). At least 1 hospitalization occurred in 15% of patients in the spironolactone group and 23% in the placebo group (=0.15). Estimated glomerular filtration rate was reduced by 6 mL/min in the spironolactone group with <1-unit reduction in controls (<0.001). Systolic blood pressure was reduced by 7.2 mm Hg (95% CI, 2.2-12.3) in the spironolactone group versus placebo (=0.005). Conclusions Spironolactone therapy does not improve exercise capacity, E/e' ratio, or quality of life in patients with chronic atrial fibrillation and preserved ejection fraction. Registration UTL: https://www.clinicaltrial.gov; Unique identifier: NCT02673463. EudraCT number 2014-003702-33.
即使接受最佳抗凝治疗，永久性房颤患者的预后、运动能力和生活质量仍较差。基于机制和观察性数据，我们检测了醛固酮受体拮抗剂螺内酯是否可以改善永久性房颤和射血分数保留患者的运动能力、E/e'比值和生活质量。
这项双盲、安慰剂对照的 IMPRESS-AF（醛固酮受体拮抗剂螺内酯对永久性房颤伴射血分数保留患者心肌纤维化所致心力衰竭运动耐量的影响）试验（NCT02673463）将 250 例稳定的永久性房颤伴左心室射血分数保留的患者随机分为螺内酯 25mg 每日组或安慰剂组。患者随访 2 年。主要疗效终点为 2 年时心肺运动试验的峰值摄氧量。次要终点包括 6 分钟步行距离、E/e'比值、生活质量和住院治疗情况。与安慰剂组相比，螺内酯治疗组 2 年时的峰值摄氧量（14.0mL/min/kg[SD，5.4]）没有改善（调整治疗效果，-0.28；95%CI，-1.27 至 0.71]；=0.58）。所有敏感性分析结果一致。6 分钟步行距离（调整治疗效果，-8.47m；-31.9 至 14.9；=0.48）、E/e'比值（调整治疗效果，-0.68；-1.52 至 0.17，=0.12）或生活质量（EuroQol-5 Dimensions，5 级版本生活质量问卷=0.74，明尼苏达心力衰竭生活质量问卷=0.84）均无差异。螺内酯组和安慰剂组各有 15%和 23%的患者至少发生了一次住院治疗（=0.15）。螺内酯组肾小球滤过率估计值较对照组降低 6mL/min（<0.001），且收缩压较安慰剂组降低 7.2mmHg（95%CI，2.2-12.3）（=0.005）。
在慢性房颤伴射血分数保留的患者中，螺内酯治疗不能改善运动能力、E/e'比值或生活质量。
UTL：https://www.clinicaltrial.gov；唯一标识符：NCT02673463。EudraCT 编号：2014-003702-33。
