Dataset Information

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial.

ABSTRACT:

Aims

To investigate the effects of spironolactone on fibrosis and cardiac function in people at increased risk of developing heart failure.

Methods and results

Randomized, open-label, blinded-endpoint trial comparing spironolactone (50 mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma B-type natriuretic peptides. The primary endpoint was the interaction between baseline serum galectin-3 and changes in serum procollagen type-III N-terminal pro-peptide (PIIINP) in participants assigned to spironolactone or control. Procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), reflecting synthesis and degradation of type-I collagen, were also measured. In 527 participants (median age 73 years, 26% women), changes in PIIINP were similar for spironolactone and control [mean difference (mdiff): -0.15; 95% confidence interval (CI) -0.44 to 0.15 μg/L; P = 0.32] but those receiving spironolactone had greater reductions in PICP (mdiff: -8.1; 95% CI -11.9 to -4.3 μg/L; P < 0.0001) and PICP/CITP ratio (mdiff: -2.9; 95% CI -4.3 to -1.5; <0.0001). No interactions with serum galectin were observed. Systolic blood pressure (mdiff: -10; 95% CI -13 to -7 mmHg; P < 0.0001), left atrial volume (mdiff: -1; 95% CI -2 to 0 mL/m2; P = 0.010), and NT-proBNP (mdiff: -57; 95% CI -81 to -33 ng/L; P < 0.0001) were reduced in those assigned spironolactone.

Conclusions

Galectin-3 did not identify greater reductions in serum concentrations of collagen biomarkers in response to spironolactone. However, spironolactone may influence type-I collagen metabolism. Whether spironolactone can delay or prevent progression to symptomatic heart failure should be investigated.

SUBMITTER: Cleland JGF

PROVIDER: S-EPMC7878013 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial.

Cleland John G F JGF Ferreira João Pedro JP Mariottoni Beatrice B Pellicori Pierpaolo P Cuthbert Joe J Verdonschot Job A J JAJ Petutschnigg Johannes J Ahmed Fozia Z FZ Cosmi Franco F Brunner La Rocca Hans-Peter HP Mamas Mamas A MA Clark Andrew L AL Edelmann Frank F Pieske Burkert B Khan Javed J McDonald Ken K Rouet Philippe P Staessen Jan A JA Mujaj Blerim B González Arantxa A Diez Javier J Hazebroek Mark M Heymans Stephane S Latini Roberto R Grojean Stéphanie S Pizard Anne A Girerd Nicolas N Rossignol Patrick P Collier Tim J TJ Zannad Faiez F

European heart journal 20210201 6

<h4>Aims</h4>To investigate the effects of spironolactone on fibrosis and cardiac function in people at increased risk of developing heart failure.<h4>Methods and results</h4>Randomized, open-label, blinded-endpoint trial comparing spironolactone (50 mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma B-type natriuretic peptides. The primary endpoint was the interaction between baseline serum galectin-3 and changes in serum procollagen typ ...[more]

PMID: 33215209

Similar Datasets

Project description:AimsIn people at risk of heart failure (HF) enrolled in the Heart 'OMics' in AGEing (HOMAGE) trial, spironolactone reduced circulating markers of collagen synthesis, natriuretic peptides, and blood pressure and improved cardiac structure and function. In the present report, we explored factors associated with dyskalaemia.Methods and resultsThe HOMAGE trial was an open-label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF. After randomization, serum potassium was assessed at 1 and 9 months and was defined as low when ≤3.5 mmol/L (hypokalaemia) and high when ≥5.5 mmol/L (hyperkalaemia). Multivariable logistic regression models were constructed to identify clinical predictors of dyskalaemia. A total of 513 participants (median age 74 years, 75% men, median estimated glomerular filtration rate 71 mL/min/1.73 m2 ) had serum potassium available and were included in this analysis. At randomization, 88 had potassium < 4.0 mmol/L, 367 had potassium 4.0-5.0 mmol/L, and 58 had potassium > 5.0 mmol/L. During follow-up, on at least one occasion, a serum potassium < 3.5 mmol/L was observed in 6 (1.2%) and <4.0 mmol/L in 46 (9%) participants, while a potassium > 5.0 mmol/L was observed in 38 (8%) and >5.5 mmol/L in 5 (1.0%) participants. The median (percentile25-75 ) increase in serum potassium with spironolactone during the study was 0.23 (0.16; 0.29) mmol/L. Because of the low incidence of dyskalaemia, for regression analysis, hypokalaemia and hyperkalaemia thresholds were set at <4.0 and >5.0 mmol/L, respectively. The occurrence of a serum potassium > 5.0 mmol/L during follow-up was positively associated with the presence of diabetes mellitus {odds ratio [OR]: 1.21 [95% confidence interval (CI) 2.14; 3.79]} and randomization to spironolactone (OR: 2.83 [95% CI 1.49; 5.37]). Conversely, the occurrence of a potassium concentration < 4.0 mmol/L was positively associated with the use of thiazides (OR: 2.39 [95% CI 1.32; 4.34]), blood urea concentration (OR: 2.15 [95% CI 1.34; 3.39] per 10 mg/dL), and history of hypertension (OR: 2.32 [95% CI 1.02; 5.29]) and negatively associated with randomization to spironolactone (OR: 0.30 [95% CI 0.18; 0.52]).ConclusionsIn people at risk for developing HF and with relatively normal renal function, spironolactone reduced the risk of hypokalaemia and, at the doses used, was not associated with the occurrence of clinically meaningful hyperkalaemia.

Project description:Background Although aldosterone antagonists improve outcomes in select individuals with heart failure and reduced ejection fraction, studies in the United States have raised concerns about underuse and overuse. Variations in the prescription of aldosterone antagonist in China are unknown. Methods and Results In the multicenter, hospital-based, retrospective China PEACE (China Patient-Centered Evaluative Assessment of Cardiac Events) study, we identified a nationally representative cohort of admissions for heart failure in a nationally representative sample of Chinese hospitals in 2015. Patients were classified into 1 of 3 groups according to their eligibility for spironolactone-"ideal" (left ventricular ejection fraction <40% and without contraindications), "contraindicated" (a documented contraindication, irrespective of left ventricular ejection fraction), and "uncertain-benefit" (all others). We measured hospital variation of spironolactone prescriptions at discharge in the "ideal" and "contraindicated" group and calculated the median odds ratio (MOR), a measure of institution-level variation for 2 individuals with similar characteristics discharged at 2 randomly selected hospitals. Hospital characteristics associated with spironolactone use were identified using multivariable linear regression model. Among 1222 ideal patients from 97 hospitals, the median rate of spironolactone prescription was 78.6% (interquartile range [IQR], 42.8%-89.6% [range, 0%-100%], MOR, 3.4 [95% CI, 2.7-4.0]) at discharge. Among 900 contraindicated patients from 83 hospitals, the median rate of spironolactone prescription was 30.0% (IQR, 9.1%-50.0% [range, 0%-100%], MOR, 3.1 [95% CI, 2.4-3.9]) at discharge. Hospitals with independent departments of cardiology and located in Eastern China were associated with a 38.0% (95% CI, 18.7-57.3; P<0.001) and a 14.6% (95% CI, 2.3%-26.9%; P=0.020) higher rate of spironolactone use for ideal patients. Conclusions In this national study of hospitals in China, the use of spironolactone among ideal patients and the inappropriate use of spironolactone among patients with contraindications was substantial, with rates that varied markedly by institution. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02877914.

Dataset Information

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial.

Aims

Methods and results

Conclusions

Publications

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial.

Similar Datasets

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