Cardiovascular R&D Centre - UnIC@RISE, Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of the University of Porto, Porto, Portugal & Internal Medicine Departament, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal; Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique 1433, U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France.
School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Int J Cardiol. 2023 Apr 15;377:86-88. doi: 10.1016/j.ijcard.2023.01.088. Epub 2023 Feb 2.
Spironolactone might improve the prognosis of patients with heart failure with preserved left ventricular ejection fraction (HFpEF), but the mechanisms by which it acts are uncertain. Serum concentrations of procollagen type I carboxy-terminal propeptide (PICP) reflect the synthesis of type I collagen and correlate well with histologically proven cardiac fibrosis.
To investigate the effect of spironolactone on serum PICP concentration in patients with stage B and C HFpEF across three trials (HOMAGE, ALDO-DHF, and TOPCAT) for which measurements of serum PICP were available.
Random-effects meta-analysis.
A total of 1038 patients with PICP measurements available both at baseline and 9-12 months were included in this analysis: 488 (47.0%) from HOMAGE, 386 (37.2%) from ALDO-DHF, and 164 (15.8%) from TOPCAT. The median (percentile) serum PICP was 98 (76-128) ng/mL. Compared to placebo or usual care, administration of spironolactone for 9 to 12 months reduced serum PICP by -7.4 ng/mL, 95%CI -13.9 to -0.9, P-value =0.02. The effect was moderately heterogeneous (I = 64%) with the most pronounced effect seen in TOPCAT where PICP was reduced by -27.0 ng/mL, followed by HOMAGE where PICP was reduced by -8.1 ng/mL, and was least marked in ALDO-DHF where PICP changed by -2.9 ng/mL. The association between spironolactone and serum PICP was not mediated substantially by blood pressure.
Spironolactone reduced serum concentrations of PICP in patients with HFpEF with different severity and stages of disease. These findings are consistent with spironolactone having an anti-fibrotic effect.
螺内酯可能改善射血分数保留的心力衰竭（HFpEF）患者的预后，但作用机制尚不确定。血清Ⅰ型前胶原羧基端前肽（PICP）浓度反映Ⅰ型胶原的合成，与组织学证实的心脏纤维化密切相关。
研究螺内酯对 3 项试验（HOMAGE、ALDO-DHF 和 TOPCAT）中 B 期和 C 期 HFpEF 患者血清 PICP 浓度的影响，这些试验均有血清 PICP 测量值。
随机效应荟萃分析。
本分析共纳入 1038 例有基线和 9-12 个月时 PICP 测量值的患者：HOMAGE 组 488 例（47.0%），ALDO-DHF 组 386 例（37.2%），TOPCAT 组 164 例（15.8%）。血清 PICP 中位数（百分位数）为 98（76-128）ng/ml。与安慰剂或常规治疗相比，螺内酯治疗 9-12 个月后血清 PICP 降低 -7.4ng/ml，95%CI-13.9 至-0.9，P 值=0.02。效应存在中度异质性（I=64%），TOPCAT 组 PICP 降低最明显，为-27.0ng/ml，其次是 HOMAGE 组，PICP 降低 8.1ng/ml，ALDO-DHF 组降低最不明显，为-2.9ng/ml。螺内酯与血清 PICP 之间的关系并未因血压而发生实质性改变。
螺内酯降低了不同严重程度和疾病阶段 HFpEF 患者的血清 PICP 浓度。这些发现与螺内酯具有抗纤维化作用一致。
