Abstract 4357831: Sacubitril/Valsartan in Resistant Hypertension: Longitudinal Improvements in Blood Pressure Control Accompanied by Increasing Adverse Event Rates

Background: Despite multidrug therapy, blood pressure control remains suboptimal in resistant hypertension, prompting evaluation of sacubitril/valsartan as an adjunct. Methods: We performed a retrospective cohort study using TriNetX to identify adults (≥18 years) with resistant hypertension initiating sacubitril/valsartan between July 1, 2016, and April 30, 2024. Resistant hypertension was defined by a prior diagnosis, use of ≥3 antihypertensives (including a diuretic and ACEi/ARB), and BP ≥140/90 mm Hg; those with prior sacubitril/valsartan use or recent pregnancy were excluded. Outcomes including AKI, MACE, mortality, BP control (≤130/80 and ≤140/90 mm Hg), and adverse events were evaluated at weeks 4, 8, 24, and 52. Results: Among 1,987 adults with resistant hypertension (mean age 63.1 ± 13 years; 66% male) initiating sacubitril/valsartan, the cumulative incidence of AKI increased from 11.7% at 4 weeks to 14.5% at 8 weeks, 19.6% at 24 weeks, and 24.2% at 52 weeks, while all-cause mortality rose from 3.6% to 5.2%, 8.3%, and 11.0%, and MACE from 14.3% to 17.8%, 23.9%, and 28.2%. Blood-pressure target attainment improved over time, with SBP ≤ 130 mm Hg achieved by 53.4%, 61.0%, 69.8%, and 74.9% at 4, 8, 24, and 52 weeks, respectively; DBP ≤ 80 by 56.2%, 63.9%, 72.0%, and 77.4%; SBP ≤ 140 by 59.1%, 66.9%, 75.4%, and 80.5%; DBP ≤ 90 by 62.8%, 70.3%, 77.9%, and 82.2%; SBP ≤ 130 or DBP ≤ 80 by 58.8%, 67.0%, 75.1%, and 79.7%; and SBP ≤ 140 or DBP ≤ 90 by 64.0%, 71.7%, 79.1%, and 83.2%. Rates of adverse events increased progressively over time: peripheral edema (2.3%, 3.6%, 6.2%, 8.8%), hypokalemia (15.9%, 19.1%, 24.9%, 30.3%), hyponatremia (20.1%, 23.5%, 29.1%, 35.3%), hyperkalemia (6.0%, 7.7%, 11.1%, 14.8%), hypernatremia (4.4%, 5.8%, 8.1%, 11.0%), headache (0.8%, 1.2%, 2.8%, 4.2%), and dizziness (1.6%, 2.6%, 5.2%, 8.2%), while serious adverse events increased from 59.4% to 67.6%, 76.4%, and 81.3% and hospitalizations from 14.2% to 19.4%, 28.1%, and 35.6%. Conclusion: Sacubitril/valsartan progressively improved BP control over 52 weeks but was associated with rising rates of AKI, MACE, and adverse events. Its use warrants a balance between antihypertensive benefit and cumulative risk.