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Spironolactone effect on circulating procollagen type I carboxy-terminal propeptide: Pooled analysis of three
João Pedro Ferreira1, John G Cleland2, Nicolas Girerd3
1Cardiovascular 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.
Insights
Spironolactone significantly reduced serum procollagen type I carboxy-terminal propeptide (PICP) levels in patients with heart failure with preserved ejection fraction (HFpEF). This suggests spironolactone has an anti-fibrotic effect in HFpEF patients.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Heart failure with preserved ejection fraction (HFpEF) prognosis may improve with spironolactone, but mechanisms are unclear.
- Serum procollagen type I carboxy-terminal propeptide (PICP) reflects type I collagen synthesis and cardiac fibrosis.
- Investigating spironolactone's effect on PICP in HFpEF patients is crucial for understanding its therapeutic actions.
Approach:
- A random-effects meta-analysis was conducted.
- Data from 1038 patients across three trials (HOMAGE, ALDO-DHF, TOPCAT) with available baseline and 9-12 month PICP measurements were analyzed.
- Spironolactone's impact on serum PICP concentration was evaluated compared to placebo or usual care.
Key Points:
- Spironolactone administration for 9-12 months reduced serum PICP by -7.4 ng/mL (95% CI -13.9 to -0.9, P=0.02).
- The effect showed moderate heterogeneity (I²=64%), with reductions observed in TOPCAT (-27.0 ng/mL), HOMAGE (-8.1 ng/mL), and ALDO-DHF (-2.9 ng/mL).
- The association between spironolactone and reduced PICP was not substantially mediated by blood pressure.
Conclusions:
- Spironolactone effectively reduced serum PICP concentrations in patients with varying severity and stages of HFpEF.
- These findings support an anti-fibrotic mechanism of action for spironolactone in HFpEF.
- Further research can explore spironolactone's role in managing cardiac fibrosis in HFpEF.
Background:
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.
Aims:
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.
Methods:
Random-effects meta-analysis.
Results:
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 (percentile25-75) 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 (I2 = 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.
Conclusions:
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.
