Sacubitril-Valsartan (LCZ696) in the Treatment of Systemic Hypertension: An Updated Review of Neprilysin Inhibition Combined with Angiotensin II Receptor Blockade

Sacubitril-valsartan (LCZ696) has been demonstrated to be a highly effective treatment for heart failure with preserved ejection fraction since its Food and Drug Administration approval in 2015, and a growing body of evidence suggests its emergence as a hypertensive medication. It acts as an inhibitor of both neprilysin and the renin-angiotensin-aldosterone system, approaching the control of a multi-faceted pathology in multiple unique ways. Because 48% of US adults are affected by hypertension, with less than half of patients achieving controlled blood pressure, and the high correlation between uncontrolled hypertension and cardiovascular mortality, it is crucial to investigate new pharmacotherapies for managing this disease. This review discusses the current evidence of sacubitril-valsartan trials in hypertension management, with a focus on distinct populations and hypertension subsets. Asian populations are predisposed to salt-sensitive hypertension and have been shown to benefit from sacubitril-valsartan more than olmesartan, an angiotensin receptor blocker (ARB). Systolic hypertension from stiff, aging arteries commonly affects individuals over the age of 65 years, and responds demonstrably better to sacubitril-valsartan than ARB monotherapy. Patients with treatment-resistant hypertension, especially those with heart failure, also show significantly improved blood pressure when treated with sacubitril-valsartan over ARBs. We conclude with a discussion of sacubitril-valsartan's potential role in managing noncardiac disease.