Efficacy of Current Standard-of-Care Treatments for Resistant Hypertension

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Current standard-of-care for resistant hypertension centers on optimized ACD therapy: ACE inhibitor or ARB, calcium channel blocker (preferably amlodipine or nifedipine), and diuretic therapy. Many patients require reoptimization of their regimen, switching from less effective agents like hydrochlorothiazide to more potent diuretics such as indapamide or chlorthalidone, and ensuring adequate dosing of all components before declaring true resistance.

The pathophysiology of resistant hypertension involves multiple unaddressed pathways beyond standard ACD therapy, including excessive sodium retention, inappropriate aldosterone production, sympathetic nervous system overactivity, and persistent vasoconstriction. These mechanisms explain why many patients require fourth-line agents, with spironolactone remaining the most evidence-based choice based on the PATHWAY-2 study demonstrating superior efficacy compared to beta blockers and alpha blockers.

Spironolactone’s limitations include adverse effects like gynecomastia and hyperkalemia risk, particularly in patients with advanced chronic kidney disease. Before initiating spironolactone, clinicians should obtain baseline aldosterone and renin levels, as these become uninterpretable once therapy begins, potentially missing opportunities for surgical treatment of primary hyperaldosteronism. For diabetic patients, ACE inhibitors or ARBs become first-line therapy when microalbuminuria is present, requiring annual ACR screening in all patients with hypertension, diabetes, or cardiovascular disease.