Rationale and methods of a randomized trial evaluating the effect of neprilysin inhibition on left ventricular remodelling.

Autor: Docherty KF; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK., Campbell RT; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK.; Queen Elizabeth University Hospital, Glasgow, UK., Brooksbank KJM; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK., Godeseth RL; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK., Forsyth P; Pharmacy Services, NHS Greater Glasgow and Clyde, Glasgow, UK., McConnachie A; Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK., Roditi G; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK.; Department of Radiology, Glasgow Royal Infirmary, Glasgow, UK., Stanley B; Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK., Welsh P; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK., Jhund PS; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK., Petrie MC; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK., McMurray JJV; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK.
Jazyk: angličtina
Zdroj: ESC heart failure [ESC Heart Fail] 2021 Feb; Vol. 8 (1), pp. 129-138. Date of Electronic Publication: 2020 Dec 10.
DOI: 10.1002/ehf2.13137
Abstrakt: Aims: In patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic, and sympatholytic effects.
Methods: We designed a randomized, double-blinded, active-comparator trial to examine the effect of sacubitril/valsartan to the current standard of care in reducing adverse LV remodelling in patients with asymptomatic LVSD following MI. Eligible patients were ≥3 months following MI, had an LV ejection fraction ≤40% as measured by echocardiography, were New York Heart Association functional classification I, tolerant of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at equivalent dose of ramipril 2.5 mg twice daily or greater, and taking a beta-blocker unless contraindicated or intolerant. Patients were randomized to sacubitril/valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). The primary endpoint will be change in LV end-systolic volume indexed for body surface area measured using cardiac magnetic resonance imaging over 52 weeks from randomization. Secondary endpoints include other magnetic resonance imaging-based metrics of LV remodelling, biomarkers associated with LV remodelling and neurohumoral activation, and change in patient well-being assessed using a patient global assessment questionnaire.
Conclusions: This trial will investigate the effect of neprilysin inhibition on LV remodelling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI.
(© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
Databáze: MEDLINE
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