Neprilysin is a neutral endopeptidase and its inhibition increases bioavailability of natriuretic peptides, bradykinin, and substance P, resulting in natriuretic, vasodilatatory, and anti-proliferative effects. In concert, these effects are prone to produce a powerful ventricular unloading and antihypertensive response. LCZ696 (Valsartan/sacubitril) is a first-in-class angiotensin II-receptor neprilysin inhibitor. LCZ696 is a novel drug not only for the treatment of heart failure but it is also likely to be a useful antihypertensive drug and may have a preferential effect on systolic pressure. This review discusses (i) the mechanism of action, pharmacokinetics, and pharmacodynamics of this novel drug, (ii) the efficacy, safety, and tolerability of LCZ696 in treatment of hypertension from the available trials, (iii) evidence from other contemporary trials on combined Neprilysin inhibitors, (iv) future trials and areas of research to identify hypertensive patient populations that would most benefit from LCZ696.

Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms [e-pub ahead of print]. Brain Behav Immun

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The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge and opportunity for translational investigators to rapidly develop safe and effective therapeutic interventions. Greater risk of severe disease in COVID-19 patients with comorbid diabetes mellitus, obesity, and heart disease may be attributable to synergistic activation of vascular inflammation pathways associated with both COVID-19 and cardiometabolic disease. This mechanistic link provides a scientific framework for translational studies of drugs developed for treatment of cardiometabolic disease as novel therapeutic interventions to mitigate inflammation and improve outcomes in patients with COVID-19.