Effect of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFpEF.
J Am Coll Cardiol
; 76(5): 503-514, 2020 08 04.
Article
in En
| MEDLINE
| ID: mdl-32731928
ABSTRACT
BACKGROUND:
Myocardial fibrosis may contribute to the pathophysiology of heart failure with preserved ejection fraction. Given the biochemical targets of sacubitril/valsartan, this study hypothesized that circulating biomarkers reflecting the mechanisms that determine extracellular matrix homeostasis are altered by sacubitril/valsartan compared with valsartan alone.OBJECTIVES:
This study investigated the effects of sacubitril/valsartan on biomarkers of extracellular matrix homeostasis and the association between biomarkers and the primary endpoint (total heart failure hospitalizations and cardiovascular death).METHODS:
N-terminal propeptide of collagen I and III, tissue inhibitor of matrix metalloproteinase 1, carboxyl-terminal telopeptide of collagen type I, and soluble ST2 were measured at baseline (n = 1,135) and 16 (n = 1,113) and 48 weeks (n = 1,016) after randomization. The effects of sacubitril/valsartan on these biomarkers were compared with those of valsartan alone. Baseline biomarker values and changes from baseline to 16 weeks were related to primary endpoint.RESULTS:
At baseline, all 5 biomarkers were higher than published referent control values. Sixteen weeks after randomization, sacubitril/valsartan decreased tissue inhibitor of matrix metalloproteinase 1 by 8% (95% confidence interval [CI] 6% to 10%; p < 0.001), soluble ST2 by 4% (95% CI 1% to 7%; p = 0.002), and N-terminal propeptide of collagen III by 3% (95% CI 0% to 6%; p = 0.04) and increased carboxyl-terminal telopeptide of collagen type I by 4% (95% CI 1% to 8%; p = 0.02) compared with valsartan alone, consistently in men and women and patients with left ventricular ejection fraction above or below the median of 57%. Higher levels of tissue inhibitor of matrix metalloproteinase 1 and soluble ST2 at baseline and increases in these markers at 16 weeks were associated with higher primary endpoint event rates.CONCLUSIONS:
Biomarkers reflecting extracellular matrix homeostasis are elevated in heart failure with preserved ejection fraction, favorably altered by sacubitril/valsartan, and have important prognostic value. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stroke Volume
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Tetrazoles
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Ventricular Function, Left
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Extracellular Matrix
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Aminobutyrates
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Heart Failure
Type of study:
Clinical_trials
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Observational_studies
/
Risk_factors_studies
Limits:
Aged
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Female
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Humans
/
Male
Language:
En
Journal:
J Am Coll Cardiol
Year:
2020
Type:
Article