Abstract Body (Do not enter title and authors here): Background
Osilodrostat, the first-generation aldosterone synthase inhibitor, lowered aldosterone and blood pressure in phase II studies, but its real-world safety and efficacy in primary hypertension remain undefined.
Methods
We used the TriNetX Global Collaborative Network to identify adults (≥18 years) initiating osilodrostat between 1 June 2020 and 30 April 2024, requiring a diagnosis of essential hypertension in the prior year and excluding secondary hypertension, spironolactone/eplerenone/finerenone use within 90 days, or pregnancy in the previous 6 months. From day +1 through 4-, 8-, 24-, and 52-weeks post-index, we assessed MACE, acute kidney injury, hyper-/hypokalemia, all-cause mortality, BP control (≤130/80 and ≤140/90 mm Hg), peripheral edema, serious adverse events, and other safety endpoints.
Results
In a cohort of 80 adults (mean age 55.1 ± 15.4 years at index; 61% women), osilodrostat therapy for essential hypertension yielded modest but progressively improving blood-pressure control over median follow-ups of 28, 56, 168, and 365 days (mean 27.7 ± 3.1, 55.0 ± 6.7, 160.5 ± 29.9, and 333.9 ± 84.5 days): SBP ≤ 130 mm Hg and DBP ≤ 80 mm Hg were achieved in 16.3% each at 4 weeks (broader target SBP ≤ 140 or DBP ≤ 90 mm Hg in 26.3%), 30% and 27.5% at 8 weeks (41.3%), 47.5% and 41.3% at 24 weeks (58.8%), and 60.0% and 58.8% at 1 year (67.5%). Prespecified adverse events—AKI, hypo-/hyperkalemia, hypo-/hypernatremia, peripheral edema, dizziness, and uric-acid elevation—occurred in ≈12.5% at each timepoint; serious adverse events rose from 13.8% at 4 weeks to 40.0% at 1 year, while MACE and all-cause mortality remained ≈12.5% throughout. Kaplan–Meier estimates showed overall survival of 97.5% at both 4 and 8 weeks, 96.2% at 24 weeks, and 90.8% at 52 weeks; freedom from hypokalemia was 91.2% at day 28 and 89% at day 56, AKI-free survival 96.1% at day 168 and 92.1% at day 365, hyperkalemia-free survival 96.2% at day 168, and serious adverse-event-free survival 70.6% at day 168 and 58.6% at day 365.
Conclusion
In 80 adults treated with osilodrostat, rates of guideline-recommended BP control rose from 16% at 4 weeks to 60% at 52 weeks, while prespecified adverse events remained stable (~12.5%) and Kaplan–Meier event-free survival was high for mortality, hypokalemia, AKI, and serious adverse events. These real-world findings support further prospective trials of aldosterone synthase inhibition in primary hypertension.