Abstract
AimsIn 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.MethodsWe 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.ConclusionsThis 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.
Highlights
Routine use of coronary reperfusion therapy has reduced the degree of ventricular damage sustained at the time of acute myocardial infarction (MI) and improved survival.[1]
The key mechanism underlying development of heart failure (HF) with reduced ejection fraction (HFrEF) following MI is the process of pathological left ventricular (LV) remodelling.[4]
It is generally accepted that patients destined to develop HFrEF after MI experience progressive LV enlargement and reduction in LV ejection fraction (LVEF), developing over weeks, months, years, or even decades after their acute coronary event
Summary
Routine use of coronary reperfusion therapy (initially with thrombolysis and latterly with percutaneous intervention) has reduced the degree of ventricular damage sustained at the time of acute myocardial infarction (MI) and improved survival.[1] Despite this, the development of left ventricular systolic dysfunction (LVSD) and subsequent heart failure (HF) after acute infarction remains relatively common.[2,3] The key mechanism underlying development of HF with reduced ejection fraction (HFrEF) following MI is the process of pathological left ventricular (LV) remodelling.[4] It is generally accepted that patients destined to develop HFrEF after MI experience progressive LV enlargement and reduction in LV ejection fraction (LVEF), developing over weeks, months, years, or even decades after their acute coronary event. Four different neurohumoral antagonists [angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists] are life-saving in both patients at high risk of HF following MI and with established chronic HFrEF.[5,6,7,8,9,10,11,12,13,14,15,16,17,18] This is unsurprising given that, in many patients, HFrEF is part of the same physiological continuum initiated at the time of acute MI
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