Sequencing Treatment for Resistant Hypertension

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Resistant hypertension affects millions of patients worldwide, requiring systematic approaches to fourth-line therapy selection. Clinical experts recommend spironolactone as the primary add-on medication for most patients with normal renal function, given its proven efficacy in resistant hypertension management. However, newer therapeutic options like endothelin receptor antagonists (aprocitentan) provide valuable alternatives for patients who cannot tolerate traditional treatments or have chronic kidney disease.

When selecting fourth-line antihypertensive agents, clinicians must evaluate individual patient factors including kidney function, electrolyte levels, and medication tolerance. Patients with elevated potassium levels or history of gynecomastia may benefit from endothelin receptor antagonists over mineralocorticoid receptor antagonists. The precision trial data demonstrates significant blood pressure reductions with aprocitentan across diverse patient populations, making it particularly valuable for patients with chronic kidney disease where renal denervation may not be appropriate.

Modern resistant hypertension management has evolved beyond routine aldosterone-to-renin ratio testing for treatment selection. Most resistant hypertension patients exhibit salt-sensitive, aldosterone-excess phenotypes regardless of laboratory values. Clinicians should focus on blood pressure response rather than biochemical markers when evaluating treatment effectiveness. The combination of multiple therapeutic approaches, including lifestyle modifications, optimal dosing of core medications, and strategic addition of fourth-line agents, provides comprehensive management strategies for complex resistant hypertension cases.