Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension: The KARDIA-2 Randomized Clinical Trial
Authors' conclusion
In patients with uncontrolled hypertension despite treatment with indapamide, amlodipine, or olmesartan, the addition of single-dose zilebesiran resulted in significant SBP reductions compared with placebo at 3 months, with low rates of serious adverse events.
Study context
- Population
- Adults with uncontrolled hypertension (24-h mean ambulatory systolic blood pressure (SBP) 130–160 mm Hg) despite indapamide, amlodipine or olmesartan1,491 entered run-in
- Participants
- 663 adults
- Comparison
- Zilebesiran vs placebo added to indapamide, amlodipine or olmesartan
- Zilebesirann = 332
- Placebon = 331reference
- Primary endpoint
- Difference between zilebesiran and placebo in change from baseline in 24-h mean ambulatory SBP, in each cohort
- Follow-up
- 3 months
Methodological detailsphase 2, double-blind, placebo-controlled, multicentre (150 sites, 8 countries)
- Phase 2
- Double-blind
- Placebo-controlled
- Multicentre (150 sites, 8 countries)
Primary result
As reported in the abstract
Change in 24-h mean ambulatory SBP
Zilebesiran vs PlaceboLeast-squares mean difference, mm Hg (95% CI)P value
Indapamide cohort
−12.1(−16.5 to −7.6)
P < 0.001Amlodipine cohort
−9.7(−12.9 to −6.6)
P < 0.001Olmesartan cohort
−4.5(−8.2 to −0.8)
P = 0.02Safety
Hyperkalemia
Hypotension · across cohorts
Acute kidney failure · across cohorts
- Hyperkalemia: across cohorts; most episodes mild and resolved without medical intervention
Original publication
Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension: The KARDIA-2 Randomized Clinical Trial. JAMA. Published 1 July 2025. doi:10.
Summarised from the published abstract; every number is checked against it