RNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial
Authors' conclusion
In adults with mild to moderate hypertension, treatment with zilebesiran across a range of doses at 3-month or 6-month intervals significantly reduced 24-hour mean ambulatory SBP at month 3.
Study context
- Population
- Adults with mild to moderate hypertension (daytime mean ambulatory systolic BP (SBP) 135 to 160 mm Hg after antihypertensive washout)377 in full analysis set
- Participants
- 394 adults
- Comparison
- Zilebesiran vs placebo
- Primary endpoint
- Between-group difference in least-squares mean (LSM) change from baseline in 24-hour mean ambulatory SBP
- Follow-up
- Month 3
Methodological detailsphase 2, double-blind, dose-ranging, placebo-controlled, 78 sites across 4 countries
- Phase 2
- Double-blind
- Dose-ranging
- Placebo-controlled
- 78 sites across 4 countries
Primary result
As reported in the abstract
24-hour mean ambulatory SBP change from baseline · 3 months
Zilebesiran 150 mg q6m
−7.3
change · 95% CI −10.3–-4.4 · mm Hg
Zilebesiran 300 mg
−10.0
change · 95% CI −12.0–-7.9 · mm Hg
Zilebesiran 600 mg q6m
−8.9
change · 95% CI −11.9–-6.0 · mm Hg
Placebo
6.8
change · 95% CI 3.6–9.9 · mm Hg
LSM difference, mm Hg (95% CI)P value
Zilebesiran 150 mg q6m vs Placebo
−14.1(−19.2 to −9.0)
P < 0.001Zilebesiran 300 mg vs Placebo
−16.7(−21.2 to −12.3)
P < 0.001Zilebesiran 600 mg q6m vs Placebo
−15.7(−20.8 to −10.6)
P < 0.001Safety
| Outcome | Zilebesiran, 150 mg, once every 6 months | Zilebesiran, 300 mg, once every 3 months or every 6 months | Zilebesiran, 600 mg, once every 6 months | Placebo | |
|---|---|---|---|---|---|
| Adverse events · 6 months | Not reported in the abstract | Not reported in the abstract | Not reported in the abstract | 50.7% | zilebesiran, 150 mg, once every 6 months, zilebesiran, 300 mg, once every 3 months or every 6 months, zilebesiran, 600 mg, once every 6 months: not reported in the abstract |
| Serious adverse events · 6 months | Not reported in the abstract | Not reported in the abstract | Not reported in the abstract | 6.7% | zilebesiran, 150 mg, once every 6 months, zilebesiran, 300 mg, once every 3 months or every 6 months, zilebesiran, 600 mg, once every 6 months: not reported in the abstract |
| Nonserious drug-related adverse events (mainly injection site reactions, mild hyperkalemia) | Not reported in the abstract | Not reported in the abstract | Not reported in the abstract | 8.0% | zilebesiran, 150 mg, once every 6 months, zilebesiran, 300 mg, once every 3 months or every 6 months, zilebesiran, 600 mg, once every 6 months: not reported in the abstract |
- Adverse events: Zilebesiran (all) 60.9%
- Serious adverse events: Zilebesiran (all) 3.6%
- Nonserious drug-related adverse events (mainly injection site reactions, mild hyperkalemia): Zilebesiran (all) 16.9%
Original publication
RNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial. JAMA. Published 5 March 2024. doi:10.
Summarised from the published abstract; every number is checked against it