Cardiovascular Medicine and Cardiac Surgery

Biography

Biography: Prashant Tarakant Upasani

Abstract

Heart failure (HF) is an increasingly common syndrome associated with high mortality and economic burden. A range of terms has been used to describe HF viz. chronic HF (CHF), acute HF (AHF), HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Pathophysiology of HFrEF is complex. Landmark trails in patient with HFrEF include SOLVD-T, CIBIS-II, CHARM-Alternative and CHARM-Added, SHIFT, EMPHASISHF and PARADIGM-HF. Natriuretic peptides (NPs) are a group of hormones that have potent effects on sodium and fluid balance. Neprilysin is a zinc-dependent metallopeptidase that catalyses the degradation of various peptides. Inhibition of neprilysin increases bioavailability of NPs, bradykinin, and substance P, resulting in natriuretic, vasodilatory and anti-proliferative effects. LCZ696 is useful not only for the treatment of HF but also likely to be a useful antihypertensive drug. LCZ696 is a novel drug that comprises sacubitril (AHU377) and valsartan in a 1:1 molar ratio. It simultaneously inhibits neprilysin and blocks AT1 receptors. PARADIGM-HF is the first study to test the efficacy of LCZ696 on morbidity and mortality in patients with HFrEF. The trail was stopped early, according to pre-specified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. LCZ696 was associated with a significantly lower death from cardiovascular causes or first hospitalization (taken together-20% or separately 20-21%). Secondary endpoint viz. death from any cause, showed a 16% reduction (p<0.001). The superiority of LCZ696 over enalapril was not accompanied by important safety concerns. The LCZ696 group had a higher proportion of patients with non-serious angioedema, but not associated with an increase in serious angioedema.