Abstract Body (Do not enter title and authors here): Background: Zilebesiran is an investigational subcutaneous (SC) RNA interference therapeutic targeting hepatic angiotensinogen synthesis. In the Phase 2 KARDIA-1 study (NCT04936035), changes in blood pressure (BP) were assessed with different zilebesiran dosing regimens as monotherapy in patients with mild-to-moderate hypertension, and clinically significant reductions in ambulatory and office systolic BP (SBP) were observed throughout the 6-month treatment period. In this analysis, we report time-adjusted changes in SBP, a measure of weighted average BP over time, assessed by three modalities: ambulatory, office, and weekly home BP monitoring.
Method: Adults with daytime mean ambulatory SBP of 135–160 mmHg were randomized equally to zilebesiran (150 mg, 300 mg, or 600 mg once every 6 months, or 300 mg once every 3 months [Q3M]) or placebo SC Q3M. Secondary and post hoc analyses included calculation of time-adjusted change in SBP from baseline through Month 3 and through Month 6 for ambulatory (24-hour mean and daytime), office, and home BP assessments. Rescue antihypertensive medication was permitted between Months 3 and 5.
Results: KARDIA-1 included 377 patients (24.7% Black, 55.7% men, mean age 56.8 years). Time-adjusted least squares mean changes in SBP (mmHg) from baseline through Month 3 for different zilebesiran doses ranged from −5.5 to –9.0 for 24-hour mean ambulatory, −5.7 to –9.2 for daytime mean ambulatory, −9.1 to −10.9 for office, and −8.3 to −9.9 for home BP assessments, compared to −0.6 to 5.6 for placebo across the different modalities (Table). Time-adjusted reductions from baseline in SBP were sustained up to Month 6. Additional measures of BP control through Month 6, including percentage of time in target range, will be presented.
Conclusion: Clinically significant time-adjusted reductions observed with self-assessed home BP following treatment with zilebesiran were consistent with ambulatory and office BP reductions, indicating that self-monitoring of BP control with zilebesiran is viable outside of the clinical visit setting. Weekly home BP measurements demonstrated consistent reductions in SBP, highlighting the potential of zilebesiran for providing sustained BP control.