Abstract | INTRODUCTION: METHODS: Clinical factors and biomarkers were evaluated as predictors of a PIIINP decrease from randomization to month 9 in 323 patients from the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Additionally, the association between PIIINP decrease and the composite of cardiovascular (CV) death or CV hospitalization were also explored. External validation was performed in the REMINDER trial. RESULTS: Female sex, eplerenone, reperfusion therapy, potassium < 4 mmol/L, circulating levels of PIIINP ≥ 3.6 ng/mL and PINP ≥ 27 ng/mL predicted a PIIINP decrease (AUC = 0.75). Randomization PIIINP showed a significant interaction with the treatment allocation: patients with PIIINP ≥ 3.6 ng/mL had a better response (decrease in PIIINP) to eplerenone (OR for PIIINP ≥ 3.6 = 2.9, 95% CI 1.46-5.89, p = 0.003) and OR for PIIINP < 3.6 = 1.09, 95% CI 0.55-2.2, p = 0.8; interactionp = 0.026). These findings were internally robust using another statistical approach (LOESS). External validation showed good discrimination (AUC = 0.70). There was a tendency toward a lower rate of CV death/CV hospitalizations in patients with decreased PIIINP (adjusted HR = 0.52, 95% CI 0.26-1.02, p = 0.058). CONCLUSION: In patients who had a myocardial infarction, clinical factors used in combination and treatment with eplerenone were associated with a PIIINP decrease. Interestingly, higher randomization PIIINP levels might help in identifying patients more prone to have an "anti-fibrotic response" when treated with MRAs. Predictors of an antifibrotic response after MI complicated by HF. Several clinical factors and biomarkers predicted a PIIINP decrease after an MI complicated by HF. There was a significant interaction between baseline PIIINP levels and eplerenone treatment: patients with baseline PIIINP ≥ 3.6 mmol/L treated with eplerenone had the best response ( PIIINP decrease).
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Authors | Susan Stienen, Patrick Rossignol, António Barros, Nicolas Girerd, Bertram Pitt, Faiez Zannad, João Pedro Ferreira |
Journal | Clinical research in cardiology : official journal of the German Cardiac Society
(Clin Res Cardiol)
Vol. 109
Issue 2
Pg. 194-204
(Feb 2020)
ISSN: 1861-0692 [Electronic] Germany |
PMID | 31250134
(Publication Type: Journal Article, Validation Study)
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Chemical References |
- Biomarkers
- Mineralocorticoid Receptor Antagonists
- Peptide Fragments
- Procollagen
- procollagen Type III-N-terminal peptide
- Eplerenone
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Topics |
- Aged
- Biomarkers
(blood)
- Clinical Decision-Making
- Eplerenone
(adverse effects, therapeutic use)
- Female
- Fibrosis
- Heart Failure
(mortality, pathology, physiopathology, prevention & control)
- Humans
- Male
- Middle Aged
- Mineralocorticoid Receptor Antagonists
(adverse effects, therapeutic use)
- Myocardium
(pathology)
- Patient Selection
- Peptide Fragments
(blood)
- Predictive Value of Tests
- Procollagen
(blood)
- Randomized Controlled Trials as Topic
- Reproducibility of Results
- Risk Factors
- ST Elevation Myocardial Infarction
(drug therapy, mortality, pathology, physiopathology)
- Time Factors
- Treatment Outcome
- Ventricular Remodeling
(drug effects)
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