ZENITH: Zilebesiran Cardiovascular Outcomes Study

Study Overview

A Phase 3, randomized, double-blind, placebo-controlled study evaluating zilebesiran, a novel RNA interference (RNAi) therapeutic targeting angiotensinogen (AGT), for reducing major adverse cardiovascular events. Zilebesiran is administered subcutaneously once every 6 months and has demonstrated sustained blood pressure reduction with an acceptable safety profile.

Inclusion Criteria

• ✓Adults ≥18 years (established CVD) or ≥55 years (high risk for CVD)
• ✓Office SBP ≥140 mmHg to <180 mmHg despite treatment
• ✓On stable therapy with at least 2 standard of care antihypertensive medications
• ✓One medication must be a thiazide, thiazide-like, or loop diuretic
• ✓Established CVD (coronary, cerebrovascular, or peripheral artery disease) OR high risk for CVD

Exclusion Criteria

• ✗Secondary hypertension
• ✗Symptomatic orthostatic hypotension
• ✗Serum potassium >4.8 mEq/L
• ✗eGFR <30 mL/min/1.73m²