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The renin–angiotensin–aldosterone system is an important regulator of blood pressure (BP), and inhibition of angiotensinogen is hypothesized as an effective treatment for hypertension. Zilebesiran is an investigational RNA interference therapy that targets angiotensinogen synthesis in the liver.
In this phase 2, double-blind, dose-ranging study of zilebesiran for mild to moderate hypertension, 394 adults (25% Black; 44% women; mean age, 57 years) were randomized to one of four doses of subcutaneous zilebesiran (150, 300, or 600 mg once every 6 months or 300 mg once every 3 months) or placebo once every 3 months. Participants had a mean daytime ambulatory systolic BP of 135 to 160 mm Hg following a washout of antihypertensive medications.
At 3…