The selective aldosterone synthase inhibitor Baxdrostat significantly lowers blood pressure in patients with resistant hypertension

Resistant hypertension is defined by blood pressure (BP) targets not achieved despite the use of at least 3 anti-hypertensive drugs of different classes, including a diuretic (1). Diagnosed in more than 10% of hypertensive patients, it represents a high-risk phenotype, leading to an increased risk of cardiovascular disease and all-cause mortality (2). A BP that cannot be controlled with the use of at least 5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic such as chlorthalidone, and spironolactone is defined refractory hypertension. Substantial evidence indicates that aldosterone excess is very common in patients with resistant hypertension and primary aldosteronism is present in ~20% of patients with confirmed resistant hypertension; intriguingly a positive relationship (more pronounced in men) between weight gain and aldosterone levels has also been demonstrated Despite its side effects (5), the mineralocorticoid receptor antagonist spironolactone remains the preferred 4 th line add-on therapy in patients with resistant hypertension. The adverse effects of spironolactone (which include reduced testosterone synthesis, hyperkalemia, gynecomastia, breast tenderness, menstrual irregularities and postmenopausal bleeding) are essentially due to the off-target blockade of several steroid hormone receptors (5). To counteract these obstacles, a different approach has Frontiers in Endocrinology frontiersin.org 01