A Randomized Trial Comparing The Effect Of Sacubitril/Valsartan To Valsartan On Left Ventricular Remodeling In Patients With Asymptomatic Left Ventricular Systolic Dysfunction After Myocardial Infarction

Introduction In patients at high risk of heart failure (HF) 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 LV remodeling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic and sympatholytic effects. In a randomized, double-blinded, active-comparator trial, we examined the effect of sacubitril/valsartan compared with the angiotensin receptor blocker (ARB), valsartan, on LV remodeling in patients with asymptomatic LVSD following MI using the gold-standard method of LV assessment, cardiac magnetic resonance imaging (MRI). Hypothesis In patients with LVSD and no evidence of HF following an MI, treatment with sacubitril/valsartan will result in a greater reduction in the degree of adverse remodeling than valsartan. Methods Key inclusion criteria were: 1) ≥3 months following MI, 2) LV ejection fraction ≤40% as measured by echocardiography, 3) tolerance of an ACE inhibitor or ARB at equivalent dose of ramipril ≥2.5mg twice daily, 4) taking a beta-blocker unless contraindicated or intolerant. Key exclusion criteria were: 1) Symptomatic HF (NYHA ≥II), 2) eGFR 5.2mmol/L, 4) symptomatic hypotension and/or systolic blood pressure Results From 7/19/2018 to 6/28/2019, 93 patients were randomized and the final study visit took place on 6/19/2020. Results from this trial will be available for presentation at the HFSA meeting. Conclusions This trial will investigate the effect of neprilysin inhibition on LV remodeling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI.