Abstract
The nonsteroidal mineralocorticoid receptor (MR) blocker esaxerenone has demonstrated good antihypertensive activity in a variety of patients, including those with uncomplicated grade I–III hypertension, hypertension with moderate renal dysfunction, hypertension with type 2 diabetes mellitus with albuminuria, and hypertension associated with primary aldosteronism. Hyperkalemia has long been recognized as a potential side effect occurring during treatment with MR blockers, but there is a lack of understanding and guidance about the appropriate management of hyperkalemia during antihypertensive therapy with MR blockers, especially in regard to the newer agent esaxerenone. In this article, we first highlight risk factors for hyperkalemia, including advanced chronic kidney disease, diabetes mellitus, cardiovascular disease, age, and use of renin-angiotensin-aldosterone system inhibitors. Next, we examine approaches to prevention and management, including potassium monitoring, diet, and the use of appropriate therapeutic techniques. Finally, we summarize the currently available data for esaxerenone and hyperkalemia. Proper management of serum potassium is required to ensure safe clinical use of MR blockers, including awareness of at-risk patient groups, choosing appropriate dosages for therapy initiation and dosage titration, and monitoring of serum potassium during therapy. It is critical that physicians take such factors into consideration to optimize MR blocker therapy in patients with hypertension.
Highlights
Mineralocorticoid receptor (MR) blockers are a class of drugs used in the treatment of essential hypertension and hyperaldosteronism and have antihypertensive effects in patients with low-renin or refractory hypertension; these effects improve prognosis in patients with heart
A systematic review showed that a combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blockers (ARBs) resulted in a small, but significant, increase in serum potassium levels [84]
The addition of spironolactone or losartan to ACE inhibitor therapy in patients with hypertension, diabetes, and albuminuria was associated with significant increases in serum potassium level compared to the outcome in the placebo group (p < 0.0001 and p = 0.03, respectively) [94]
Summary
Mineralocorticoid receptor (MR) blockers are a class of drugs used in the treatment of essential hypertension and hyperaldosteronism and have antihypertensive effects in patients with low-renin or refractory (resistant) hypertension; these effects improve prognosis in patients with heart. These trials included patients with essential hypertension, hypertension with moderate renal impairment, hypertension with type 2 diabetes and albuminuria, and primary aldosteronism, and esaxerenone was given alone or in combination with RAS inhibitors or CCBs (Daiichi Sankyo Co., Ltd., unpublished data, J305, and J307 studies; and published data [25–28]). In the recently published J306 study, esaxerenone was administered over 12 weeks at a starting dosage of 1.25 mg/day and was gradually titrated to 2.5 mg/day and 5 mg/day at weeks 4, 6, or 8 based mainly on serum potassium levels but with reference to other patient factors such as eGFR and blood pressure [26] In this case, 1/51 patients had consecutive serum potassium measurements >5.5 mEq/L, but this elevated level resolved following dosage reduction, indicating that careful monitoring and treatment modulation can be helpful in minimizing hyperkalemic risk. Data are shown as n (%) ARB angiotensin II-receptor blockers, ACE angiotensin-converting enzyme aIncludes all patients with serum potassium elevation, whether or not elevated potassium was reported as a side effect bNon-approved administration regimen
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