Aldosterone Synthase Inhibitors: The New Frontier in Hypertension Management?

12 Sept 2023 • Once-daily treatment with the selective aldosterone synthase inhibitor lorundrostat safely and significantly reduced blood pressure in adults with uncontrolled hypertension in a phase 2 randomized controlled trial. Results of the Target-HTN trial were published in the Journal of the American Medical Association to coincide with presentation at the American Heart Association (AHA) 2023 Hypertension Scientific Sessions.

KEY POINTS Question: Among patients with uncontrolled hypertension, does the aldosterone synthase inhibitor lorundrostat safely lower blood pressure?

Findings In this randomized clinical trial that included 200 participants, lorundrostat decreased blood pressure significantly more than placebo with 50-mg and 100-mg once-daily doses, and adverse events, including hyperkalemia, were uncommon.

Implications for practice Aldosterone synthase inhibition with lorundrostat showed potential for blood pressure lowering in patients with hypertension that was inadequately controlled despite background antihypertensive treatment.

Contemporary guidance for treatment of resistant hypertension advocates for use of mineralocorticoid receptor antagonists (MRAs) following treatment with a 3-drug regimen of a thiazide-type diuretic, a dihydropyridine calcium channel blocker, and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. However, antiandrogenic- and progestogenic-related adverse effects are common barriers to wider MRA use, particularly use of spironolactone. Decreasing aldosterone production via inhibition of aldosterone synthase, rather than blocking the mineralocorticoid receptor, may avoid these adverse effects. Lorundrostat is a selective inhibitor of aldosterone synthase currently under investigation.

The trial results support further study of lorundrostat as a treatment for uncontrolled hypertension.

Source: JAMA | Read full story

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