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Zilebesiran Reduces SBP on Background SOC in Uncontrolled HTN: Daily Dose

Zilebesiran Reduces SBP on Background SOC in Uncontrolled HTN: Daily Dose / Image Credit: ©New Africa/AdobeStock
©New Africa/AdobeStock

Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

Last week, we reported on findings from a study presented at the American College of Cardiology’s 73rd Annual Scientific Session, held April 6-8, 2024, in Atlanta, Georgia.

The study

The KARDIA-2 study evaluated the efficacy and safety of zilebesiran added to standard-of-care antihypertensive treatment in 672 adults with mild-to-moderate hypertension that remained uncontrolled despite up to 2 antihypertensive medications. At the start of a 4-week run-in period, all previous hypertension medications were discontinued and study participants were randomly assigned to open label treatment with once-daily oral olmesartan (20 or 40 mg), amlodipine (5 mg) or indapamide (2.5 mg). Those eligible after the run-in period, participants with 24-hour (24h) mean SBP of 130-160 mm Hg, were randomly assigned in a 1:1 ratio to receive a single subcutaneous dose of 600 mg zilebesiran or placebo as add-on therapy to the protocol-specified background antihypertensive medication for 6 months.

The study’s primary endpoint was the change from baseline in mean SBP at month 3, assessed by 24h ABPM (ambulatory blood pressure monitoring). Key secondary endpoints included change from baseline to month 3 in office SBP and time-adjusted change from baseline to month 6 in 24h mean ambulatory and office SBP.

KARDIA-2 study participants had a mean age of 59 years; 43% were women and 28% were Black. Approximately 1 in 4 patients had diabetes other than type 1 in addition to hypertension. Average SBP among participants before receiving zilebesiran or placebo was 143 mmHg.

The findings

Researchers reported that at 3 months, participants receiving zilebesiran in each of the 3 SOC groups experienced significant additional reductions in 24h ambulatory SBP vs placebo. Average incremental reductions for each were:

  • indapamide 12 mmHg

  • amlodipine 9.7 mmHg

  • olmesartan 4 mmHg

Authors' comment

“The fact that zilebesiran treatment resulted in significant reductions in blood pressure on top of each background treatment at three months—which persisted to six months in many cases even with treatment with additional medications—suggests that it may be a very potent new strategy for lowering blood pressure while reducing the need for daily pills."

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