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<p>Hypertension affects over one billion individuals worldwide and remains the leading modifiable risk factor for cardiovascular disease. While first-line therapies including thiazide-type diuretics, angiotensin converting enzyme inhibitors / angiotensin receptor blockers, and calcium channel blockers can effectively control blood pressure in many patients, 10–20% develop resistant hypertension requiring additional therapeutic approaches. Steroidal mineralocorticoid receptor antagonists (MRAs) have emerged as essential fourth-line agents for resistant hypertension, with spironolactone demonstrating superior efficacy compared to other add-on therapies in the landmark PATHWAY-2 trial. The pathophysiological rationale for MRAs includes natriuretic effects, vasodilatory properties and target organ protection through anti-fibrotic mechanisms. Novel non-steroidal MRAs offer improved selectivity and reduced endocrine side effects compared to traditional agents, potentially expanding the therapeutic window for mineralocorticoid receptor blockade. In this review, we discuss the established role of MRAs in primary and resistant hypertension management and discuss consideration of MRAs in certain hypertension patient populations. We also briefly review patient selection strategies and future directions for this important therapeutic class.</p>

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The Role of Mineralocorticoid Receptors in the Treatment of Primary Hypertension

  • 期刊论文

  • 发表日期：

    2026年1月5日

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  • Jehan Zahid Bahrainwala,
  • Vivek Bhalla

摘要

Hypertension affects over one billion individuals worldwide and remains the leading modifiable risk factor for cardiovascular disease. While first-line therapies including thiazide-type diuretics, angiotensin converting enzyme inhibitors / angiotensin receptor blockers, and calcium channel blockers can effectively control blood pressure in many patients, 10–20% develop resistant hypertension requiring additional therapeutic approaches. Steroidal mineralocorticoid receptor antagonists (MRAs) have emerged as essential fourth-line agents for resistant hypertension, with spironolactone demonstrating superior efficacy compared to other add-on therapies in the landmark PATHWAY-2 trial. The pathophysiological rationale for MRAs includes natriuretic effects, vasodilatory properties and target organ protection through anti-fibrotic mechanisms. Novel non-steroidal MRAs offer improved selectivity and reduced endocrine side effects compared to traditional agents, potentially expanding the therapeutic window for mineralocorticoid receptor blockade. In this review, we discuss the established role of MRAs in primary and resistant hypertension management and discuss consideration of MRAs in certain hypertension patient populations. We also briefly review patient selection strategies and future directions for this important therapeutic class.