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A single subcutaneous dose of zilebesiran was associated with a reduction in mean ambulatory and office systolic blood pressure.
When added to standard-of-care antihypertensives, a single subcutaneous dose of zilebesiran was associated with a clinically significant reduction in mean ambulatory and office systolic blood pressure (SBP) at month 3. Moreover, the novel BP-lowering drug showed a promising safety profile in the phase KARDIA-2 trial.
Zilebesiran, an investigational RNA interference therapeutic, has previously shown promising outcomes in hypertension management.1 The current KARDIA-2 study (NCT05103332), presented by Akshay Desai, MD, MPH, FHFSA, aimed to assess zilebesiran‘s efficacy in combination with standard-of-care antihypertensive therapy.2
The study enrolled 1,500 adults with mild-to-moderate hypertension who were randomized to receive once-daily oral treatment with olmesartan, amlodipine, or indapamide as background therapy. Those with a 24-hour mean SBP of 130–160 mm Hg for at least 4 weeks were further randomized to receive zilebesiran 600 mg or placebo as add-on therapy.
At 3 months, participants receiving zilebesiran with either indapamide, amlodipine, or olmesartan demonstrated statistically significant reductions in 24-hour mean ambulatory SBP and office SBP compared with placebo. The least-square mean differences (LSMDs) were -12.1 mm Hg for zilebesiran + indapamide, -9.7 mm Hg for zilebesiran + amlodipine, and -4.0 mm Hg for zilebesiran + olmesartan were (all P<0.001). At 6 months, reductions in office SBP remained significant (all P<0.001) for zilebesiran + indapamide (-13.6 mm Hg), zilebesiran + amlodipine (-8.6 mm Hg), and zilebesiran + olmesartan (-4.6 mm Hg).
Safety analysis revealed a favorable profile for all combinations, with low incidences of adverse events (AEs) and rare serious AEs. Notably, hypotension/orthostatic hypotension occurred in 7 participants in each combination group but was resolved without intervention. A few participants experienced greater than 30% reduction in eGFR, primarily in the first 3 months, which resolved upon repeat measurement.
“Although our trial was not adequately powered or of sufficient duration to ensure long-term safety and efficacy, these results do appear to support the potential for combining biannual dosing of zilebesiran with standard-of-care or any hypertensives to achieve additive blood pressure reductions”, concluded Dr. Desai.
Medical writing support was provided by Dr Susanne Kammerer
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