KARDIA-3: ZILEBESIRAN AS ADD-ON THERAPY IN ADULTS WITH HYPERTENSION AND ESTABLISHED CARDIOVASCULAR DISEASE OR HIGH CARDIOVASCULAR RISK WITH AND WITHOUT CHRONIC KIDNEY DISEASE

Objective: Zilebesiran is an investigational RNA interference therapeutic that reduces hepatic angiotensinogen production, with potential to improve continuous control of blood pressure (BP) with 6-monthly subcutaneous dosing. KARDIA-3 evaluated zilebesiran in patients with uncontrolled hypertension at high cardiovascular (CV) risk, with or without chronic kidney disease, to inform the design of a Phase 3 CV outcomes trial. Design and method: KARDIA-3 was a Phase 2, randomized, double-blind, placebo-controlled trial (NCT06272487). Eligible patients had established CV disease or high CV risk, uncontrolled hypertension (mean office systolic BP 140–170 mmHg at screening, and 24-hour mean ambulatory systolic BP 130–170 mmHg within 7 days before randomization), while treated with 2–4 antihypertensives. Patients in Cohort A (eGFR >=45 mL/min/1.73 m2) were randomized 1:1:1 to a single subcutaneous dose of zilebesiran 300 mg, 600 mg, or placebo; those in Cohort B (eGFR 30 to