Can baxdrostat revamp resistant hypertension status in India?

To the Editor, When a patient has resistance hypertension (RH), his or her blood pressure remains higher than 130/80 mmHg even after taking a combination of three or more different classes of antihypertensive medications, such as a diuretic, a calcium channel blocker, and a renin–angiotensin–aldosterone system blocker.[1,2] In India, 19% of people have RH.[3] RH is becoming one of the main causes of death. High intake of alcohol and salt, inadequate adherence, physical inactivity, diabetes, obesity, women, black racial group, and reduced renal function are the variables linked to RH. Patients who have pheochromocytoma, Conn’s syndrome, or thyroid disorders may also have RH. Excess aldosterone has recently been proposed as a key factor causing RH. Two-thirds of people with RH have low renin. As a result, the recommended course of treatment should involve consuming less salt, taking diuretics at higher dosages, and using mineralocorticoid receptor antagonists such as eplerenone and spironolactone. However, because the latter is less effective and the former is linked to several side effects, such as hyperkalemia, its usage is severely restricted. Another option Another option to control the dangerous harmful effects of aldosterone excess is by using aldosterone synthase inhibitor (ASIs) such as baxdrostat. The small molecule medication baxdrostat works by blocking the enzyme aldosterone synthase, also known as CYP11B2, which controls the latter stages of aldosterone synthesis. Because it has 93% sequential similarity to CY11B1, the enzyme that catalyzes the cortisol synthesis pathway, its strong selectivity for CYP11B2 enzyme is advantageous [Figure 1]. Earlier ASIs were less effective because they hindered the production of cortisol due to their high cross-reactivity. However, baxdrostat was found to have a less substantial influence on plasma cortisol levels as explained by Freeman et al.[4]Figure 1: Pathway of Aldosterone synthesisWhen administered as a single daily dose of 2 mg, baxdrostat significantly reduced both the diastolic and systolic blood pressure. Its half-life is between 26 and 31 h. Headache, exhaustion, urinary tract infection, and hyperkalemia were the reported side responses. Because they did not experience cardiac arrhythmia, the patients with elevated potassium levels did not require medication discontinuation.[4] There have been no reports of androgenic side effects because it does not lower plasma cortisol levels. In healthy populations, no contraindications have been discovered too yet. Many trials are currently being conducted to investigate the added role of baxdrostat in uncontrolled hypertension, chronic kidney disease (CKD), and primary hyperaldosteronism. These trials include the HALO, HTN-CKD trial, and Spark-PA. According to the results of an open-level extension trial, baxdrostat inhibited the renal transporters MATE-1 and MATE-2K, which regulate the removal of metformin.[5] Therefore, when metformin is administered with baxdrostat, there is no need to change the dosage. Baxdrostat is a novel drug showing promising results in resistant hypertension. As elevated aldosterone levels are implicated in the pathophysiology of diseases such as insulin resistance, obesity, metabolic syndrome, and CKD which are on the rise in our country, ASIs can be beneficial. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.