Efficacy of Tonlamarsen in Patients With Uncontrolled Hypertension: The KARDINAL Phase 2 Randomized Clinical Trial
Authors' conclusion
Among individuals with uncontrolled hypertension, monthly tonlamarsen administration was more effective at lowering plasma angiotensinogen compared with a single tonlamarsen dose, but there was no additional BP reduction.
Study context
- Population
- Adults with uncontrolled hypertension: office SBP >135 mm Hg on 2 to 5 antihypertensive medicationsrandomized
- Participants
- 198 adults
- Comparison
- Monthly tonlamarsen vs single dose of tonlamarsen and subsequent placebo
- Primary endpoint
- Coprimary: between-group differences in change from baseline in plasma angiotensinogen and in office SBP
- Follow-up
- Week 20
Methodological detailsplacebo-controlled, 4-week placebo lead-in, 4-week active run-in
- Placebo-controlled
- 4-week placebo lead-in
- 4-week active run-in
Primary result
As reported in the abstract
20 weeks after first dose
Single dose then placebo
- Plasma angiotensinogen % change
- −23.0% (95% CI: −27.8% to −18.2%)
- Office SBP change
- −6.7 mm Hg (95% CI: −9.8 to −3.5 mm Hg)
Monthly tonlamarsen
- Plasma angiotensinogen % change
- −67.2% (95% CI: −71.9% to −62.4%)
- Office SBP change
- −6.7 mm Hg (95% CI: −9.8 to −3.6 mm Hg)
Plasma angiotensinogen % change
Single dose then placebo−23.0% (95% CI: −27.8% to −18.2%)
Monthly tonlamarsen−67.2% (95% CI: −71.9% to −62.4%)
Office SBP change
Single dose then placebo−6.7 mm Hg (95% CI: −9.8 to −3.5 mm Hg)
Monthly tonlamarsen−6.7 mm Hg (95% CI: −9.8 to −3.6 mm Hg)
Monthly tonlamarsen vs Single dose then placeboLS mean difference, % (97.5% CI)P value
Plasma angiotensinogen
−44.1(−51.9% to −36.4%)
P < 0.0001- Office SBP
- Least squares (LS) mean difference −0.1 mm Hg (95% CI −4.5 to −4.4 mm Hg); P = 0.97
Safety
Serious adverse events
- Infrequent and similar between treatment groups
Original publication
Efficacy of Tonlamarsen in Patients With Uncontrolled Hypertension: The KARDINAL Phase 2 Randomized Clinical Trial. J Am Coll Cardiol. Published 28 March 2026. doi:10.
Summarised from the published abstract; every number is checked against it