Consistent Antihypertensive Efficacy of the RNA Interference Therapeutic Zilebesiran: Subgroup Results from the Kardia-1 Phase 2 Study
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2024
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Conference Proceedings
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Background In the randomized, double-blind, dose-ranging KARDIA-1 study, zilebesiran significantly reduced 24-h mean ambulatory systolic blood pressure (SBP) versus placebo at Month 3 (primary endpoint). This analysis assessed zilebesiran efficacy and safety in patient subgroups. Methods Patients with daytime mean ambulatory SBP of 135-160 mmHg following antihypertensive washout were randomized to subcutaneous zilebesiran (150 mg, 300 mg, or 600 mg once every 6 months, or 300 mg once every 3 months) or placebo for 6 months. Evaluated subgroups included age (=65 years), sex, race (black; other), baseline 24-h mean SBP (=145 mmHg), eGFR (=60 mL/min/1.73m2), and baseline plasma renin concentration (PRC) (median 11 mIU/L). Least-square mean difference versus placebo in change from baseline in 24-h mean ambulatory SBP was reported at Month 3. Results Across zilebesiran regimens, consistent reductions in 24-h mean SBP from baseline to Month 3 versus placebo were observed in examined subgroups. Significantly greater antihypertensive response was observed in patients with baseline PRC >11 mIU/L versus <=11 mIU/L (p=0.040). AEs were reported in 50.7-64.3% of zilebesiran patients across subgroups, with no apparent increased risk with zilebesiran versus placebo in any examined subgroup. Conclusion The antihypertensive efficacy and safety of zilebesiran versus placebo were consistent across subgroups. Higher baseline PRC was associated with larger SBP reductions at Month 3. [Formula presented]
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Journal of the American College of Cardiology
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ACC.24.