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

Abstract

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 (3,4). 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

Therapeutic concordance improves blood pressure control in patients with resistant hypertension

“…TRH is defined as the failure to achieve target BP when a patient is treated with maximal doses of 3 antihypertensive drugs including a diuretic. TRH is not equivalent to uncontrolled hypertension, as patients with TRH might achieve target BP with full doses of 4 or more medications [ 22 , 54 ].…”

“…However, relatively little is known on the hypertensive patients’ perspectives in terms of the management of their illness and their views on concordance. Since an empathetic approach to hypertensive patients with multiple comorbidities and polypharmacy may be particularly useful in patients with therapy-resistant hypertension (TRH), defined as the failure to achieve target BP when a patient is treated with maximal doses of 3 antihypertensive drugs including a diuretic [ 22 ], we designed a study to explore the impact of therapeutic concordance in TRH patients.…”

Associated factors and hemodynamic characteristics of resistant hypertension in the elderly

“…Angiotensin receptor neprilysin inhibitors instead of renin‐angiotensin system inhibition alone may be a better choice for RHTN, as the potential mechanisms include reductions in circulating volume and sympathetic activity 30,31 . Recent researches show the selective aldosterone synthase inhibitor Baxdrostat significantly lowers BP in patients with RHTN, as aldosterone excess is common in RHTN 32 …”

Aldosterone Synthase Inhibitors and Dietary Interventions: A Combined Novel Approach for Prevention and Treatment of Cardiovascular Disease

“…Another Freeman et al ( 2022) study evaluated baxdrostat in patients with treatment-resistant HTN [12]. Baxdrostat is shown to selectively inhibit AS without affecting 11-beta-hydroxylase [24]. The trial was discontinued early at 12 weeks due to its effectiveness criteria being met.…”