Randomized placebo-controlled cardiovascular outcomes trials of pharmacological blood pressure lowering were performed already inthe1960s, andthescientificevidencesupporting the use of antihypertensive drugs as a cornerstone for cardiovascular protection has grown ever since.1 Today, 4 classes of antihypertensive drugs are considered the most rational drugs of choice because of their proven ability to reduce the incidence of cardiovascular events: inhibitors of the reninangiotensin system (angiotensin converting enzyme inhibitors and angiotensin receptor blockers), calcium channel blockers, thiazides and related diuretics, and beta blockers. Emerging drug classes that appear on the horizon include selective aldosterone synthase inhibitors, dual blockers of endothelin hypertension were randomized to treatment with either the angiotensin receptor blocker olmesartan (20 mgdaily) orto1of2doses(240or480mgdaily)of the novel angiotensin receptor neprilysin inhibitor sacubitril/allisartan. Patients were included based on their systolic office blood pressure, which was required to be 150 to 179 mm Hg at study initiation, following a wash-out period during which participants on prior antihypertensive therapy (approximately 90% of the study cohort) terminated their treatment. After 12 weeks of treatment, the baseline-adjusted changes in office systolic blood pressure (which was the primary outcome) was 23 mmHgwitholmesartan 20 mg daily, 25 mm Hg receptorsAandB,andinjectableblockersofhepatic angiotensinogen mRNA synthesis.2