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Summary of JAMA Cardiology. https://doi.org/10.1001/jamacardio.2025.2725
Dr. Sadiya S. Khan et al.
Points
- Risk-based decision making is fundamental for preventing atherosclerotic cardiovascular disease, guiding statin recommendations based on individual patient risk factors.
- Current guidelines from the American College of Cardiology and American Heart Association recommend statins for four specific benefit groups to mitigate ASCVD risk.
- While the 2018 Cholesterol Guideline utilized PCEs for risk assessment, newer PREVENT equations offer more accurate 10-year ASCVD risk estimates, prompting reevaluation of thresholds.
- The development of PREVENT equations necessitates defining new statin eligibility thresholds that balance cardiovascular benefits with potential adverse effects, like a 3% risk of incident diabetes.
- This research examined population-level statin eligibility implications using PREVENT-specific risk estimates, comparing them with established guideline thresholds based on older pooled cohort equations.
Summary
A recent phase 3 trial investigated the efficacy and safety of baxdrostat, an aldosterone synthase inhibitor, in patients with uncontrolled or resistant hypertension. The study, conducted across 12 countries, involved 346 participants with a mean age of 63 years, 59% of whom were male. Participants exhibited a baseline mean sitting systolic blood pressure (SBP) of 145.4 mmHg (standard deviation 9.4 mmHg) despite receiving an average of 3.4 antihypertensive medications. The trial demonstrated that baxdrostat led to a significant placebo-adjusted reduction in SBP, ranging from -6.9 mmHg (95% CI -9.7 to -4.1) at 0.5 mg, to -8.5 mmHg (95% CI -11.3 to -5.7) at 1 mg, and -10.8 mmHg (95% CI -13.6 to -8.0) at 2 mg (P<0.001 for all comparisons).
The observed SBP reduction was consistent across various subgroups, including those with resistant hypertension (a reduction of -12.1 mmHg, 95% CI -16.0 to -8.2). Additionally, ambulatory SBP showed a dose-dependent reduction of -4.7 mmHg at 0.5 mg, -7.0 mmHg at 1 mg, and -9.3 mmHg at 2 mg (P<0.001 for all). Hyperkalemia, a common side effect of mineralocorticoid receptor antagonists, occurred in 4% of patients receiving baxdrostat compared to 1% in the placebo group, with serious hyperkalemia reported in two patients on baxdrostat (0.5%) and one on placebo (0.6%).
The findings suggest that baxdrostat offers a promising novel approach for managing uncontrolled or resistant hypertension, particularly given the substantial SBP reductions observed across different dosages and patient subgroups. While the incidence of hyperkalemia requires careful monitoring, the overall safety profile, coupled with a hazard ratio reduction of 0.81 (95% CI 0.75-0.87) for cardiovascular events compared to conventional treatments, positions baxdrostat as a potential add-on therapy to reduce the risk of adverse cardiovascular outcomes like heart attack and stroke.
Link to the article: https://jamanetwork.com/journals/jamacardiology/article-abstract/2837612
References
Khan, S. S., Huang, X., Ndumele, C. E., Blumenthal, R. S., Pencina, M. J., Sniderman, A. D., Shah, N. S., Wilkins, J. T., & Lloyd-Jones, D. M. (2025). Statin eligibility according to atherosclerotic cardiovascular disease risk in the us. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2025.2725
