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KardinalLBCT-IIHypertensionJournal of the American College of Cardiology
Efficacy of Tonlamarsen in Uncontrolled Hypertension Treatment
Efficacy of Tonlamarsen in Patients With Uncontrolled Hypertension
View Full PaperLuke J. Laffin, MD, is a physician in the Preventive Cardiology & Rehabilitation Section of the Department of Cardiovascular Medicine at Cleveland Clinic. He serves as Co-Director of the Center for Blood Pressure Disorders at Cleveland Clinic. His practice focuses on hypertension, cardiovascular risk modification, and preventive cardiology.
Overview
Single-dose tonlamarsen achieves equivalent BP reduction without monthly dosing; challenges assumptions of greater target suppression yielding added efficacy.
Key result
Monthly tonlamarsen administration reduced plasma angiotensinogen more than a single dose (difference -44.1%; P<0.0001) but provided no additional systolic BP reduction (difference -0.1 mm Hg; P=0.97).
Discussion
Kardinal has reported — post the first read.
Key Points
- This research aimed to evaluate the safety and efficacy of tonlamarsen in lowering blood pressure in patients with uncontrolled hypertension.
- Randomized, placebo-controlled trial design
- Enrolled adults with systolic BP >135 mm Hg on multiple antihypertensive medications
- Administered tonlamarsen monthly for 5 months, comparing with placebo.
- Plasma angiotensinogen levels decreased by -67.2% with monthly tonlamarsen vs. -23.0% with a single dose (P < 0.0001).
- Office systolic BP reduction was -6.7 mm Hg for both treatment groups, showing no significant difference (P = 0.97).
- Serious adverse events were rare and similar between treatment groups.
Study Design
Type
RCT (n=198)
Blinding
Placebo-controlled
Randomization
Randomized
Structured PICO
Does monthly tonlamarsen reduce plasma angiotensinogen and office systolic BP compared to a single dose in adults with uncontrolled hypertension?
P
Population
198 randomized adults with uncontrolled hypertension (office systolic BP >135 mm Hg) receiving 2 to 5 antihypertensive medications.
I
Intervention
Tonlamarsen 90 mg administered subcutaneously once monthly for 5 months (1 dose during active run-in followed by 4 additional doses).
C
Comparator
A single dose of tonlamarsen 90 mg subcutaneously (during active run-in) followed by matching placebo for 16 weeks.
O
Outcome
Coprimary endpoints: between-group differences in the change from baseline to week 20 in plasma angiotensinogen and in office systolic BP.surrogate
Monthly administration of the antisense oligonucleotide tonlamarsen effectively lowers plasma angiotensinogen but does not provide additional blood pressure reduction compared to a single dose in patients with uncontrolled hypertension.
Main Result
Effect estimate: LS mean difference -0.1 mm Hg (95% CI -4.5 to -4.4)
Absolute Event Rate: -6.7% vs -6.7%
p-value: p=0.97
Trending Research#20 this week
The KARDINAL trial, presented at ACC.26 and published in JACC, showed mixed results for the novel hypertension drug tonlamarsen. While it effectively lowered its target protein, the blood pressure effects were complex, sparking discussion about this new therapeutic pathway and future trial design.
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