1. Trial Focus (KARDIA-1):
•Examined subcutaneous
zilebesiran's impact on
systolic blood pressure.
Outcome:
•Demonstrated
sustained reduction in
systolic blood pressure.
Patient Group:
•Patients with
hypertension were the
focus of the trial.
Zilebesiran Description:
•Subcutaneous injectable.
•Targets hepatic
angiotensinogen (AGT)
synthesis.
Mechanism:
•Operates through RNA
interference.
Objective:
•Evaluated zilebesiran
effectiveness compared to
a placebo.
Contribution to Literature:
•Provides valuable evidence on the sustained reduction in systolic blood pressure
with subcutaneous zilebesiran, contributing to hypertension literature.
Presented by Dr. George Bakris at the American Heart Association Scientific Sessions, Philadelphia, PA, November 11, 2023
2. Design:
Randomized,
Parallel, Blinded,
Placebo-controlled.
Enrollment:
Total Patients: 378
Mean Age: 57 years
Female Percentage: 44%
Inclusion Criteria:
Age 18-75
Daytime systolic blood
pressure ≥135 mm Hg and
≤160 mm Hg
Interventions:
Randomized groups:
Zilebesiran 150 mg every 6 months
Zilebesiran 300 mg every 6 months
Zilebesiran 300 mg every 3 months
Zilebesiran 600 mg every 6 months
Placebo
Follow-up:
6 months
Presented by Dr. George Bakris at the American Heart Association Scientific Sessions, Philadelphia, PA, November 11, 2023
3. Dosage
Zilebesir
an 150
mg
Zilebesir
an 300
mg
Zilebesir
an 300
mg (3
months)
Zilebesir
an 600
mg
Change -11.1 -14.5 -4.1 -14.2
Primary Outcome - Change in Ambulatory
Systolic Blood Pressure (mm Hg) vs. Placebo:
Secondary Outcomes - Change in Office
Systolic Blood Pressure (mm Hg) vs. Placebo:
Dosage
Zilebesiran
150 mg
Zilebesiran
300 mg
Zilebesiran
300 mg (3
months)
Zilebesiran
600 mg
Change -7.5 -10.5 -12.1 -10.2
Serum AGT Level Reduction (%):
Dosage
Zilebesiran
150 mg
Zilebesiran
300 mg
Zilebesiran
300 mg (3
months)
Zilebesiran
600 mg
Reduction 88% 93% 98% 96%
Presented by Dr. George Bakris at the American Heart Association Scientific Sessions, Philadelphia, PA, November 11, 2023
4. •Background:
• LBBAP may be more effective than BVP in cardiac resynchronization therapy (CRT), improving left
ventricular ejection fraction and reducing heart failure hospitalization.
•Objective:
• Compare the occurrence of sustained ventricular tachycardia or ventricular fibrillation (VT/VF) and
new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP for CRT.
Study Design (I-CLAS):
•Included patients with LVEF≤35%
undergoing BVP or LBBAP for CRT from
Jan 2018 to June 2022 at 15 centers.
•Conducted propensity score-matched
(PS) analysis in a 1:1 ratio.
Patient Population:
•Total CRT patients: 1778 (BVP:
981, LBBAP: 797).
•PS-matched patients: 1414 (PS-
BVP: 707, PS-LBBAP: 707).
Herweg B, Sharma PS, Cano O, Ponnusamy SS, Zanon F, Jastrzebski M, Zou J, Chelu MG, Vernooy K, Whinnett ZI, Nair GM, Molina-Lerma M, Curila K, Zalavadia D, Dye C, Vipparthy SC, Brunetti R, Mumtaz M, Moskal P, Leong AM, van Stipdonk A, George J,
Qadeer YK, Kolominsky J, Golian M, Morcos R, Marcantoni L, Subzposh FA, Ellenbogen KA, Vijayaraman P. Arrhythmic Risk In Biventricular Pacing Compared with Left Bundle Branch Area Pacing: Results From The International LBBAP Collaborative Study (I-
CLAS). Circulation. 2023 Nov 11. doi: 10.1161/CIRCULATIONAHA.123.067465. Epub ahead of print. PMID: 37950738.
