Resistant Hypertension Management

Resistant hypertension definition (AHA/ESC 2018-2023): BP remains >140/90 mmHg (or >130/80 in high-risk) despite optimal doses of three antihypertensives from different classes (RAAS blocker + CCB + thiazide-like diuretic) OR controlled BP requiring ≥4 drugs. Refractory hypertension: uncontrolled despite ≥5 drugs (more severe phenotype). Pseudo-resistant must be excluded first: 1) Non-adherence (50-80% of cases) - urine/serum drug screening, DOT, pill counting; 2) White-coat effect - 24-hour ABPM mandatory; 3) Suboptimal dose - escalate before adding; 4) Inappropriate combinations.

Secondary cause workup: 1) Primary aldosteronism (PA) - 20% prevalence in resistant HT; aldosterone-renin ratio (ARR), salt-loading test; treat with spironolactone or adrenalectomy; 2) Renal artery stenosis - duplex US, CTA, MRA; FMD vs atherosclerotic; revascularization in select cases; 3) OSA - polysomnography (STOP-BANG); CPAP reduces nocturnal BP; 4) Pheochromocytoma - plasma metanephrines, 24-hour urine; 5) Cushing syndrome - 1-mg dexamethasone suppression, 24-hour urinary cortisol; 6) Coarctation, thyroid disease, drug-induced (NSAIDs, COCs, decongestants, licorice).

Treatment algorithm (PATHWAY-2 evidence): Step 1) Optimize triple therapy - ACEi/ARB + dihydropyridine CCB + chlorthalidone/indapamide (thiazide-like preferred over hydrochlorothiazide); Step 2) Add spironolactone 25-50 mg/day (most effective fourth agent in PATHWAY-2 trial; check K+ and creatinine); Step 3) Alternative fourth agent if hyperkalemia/CKD - eplerenone, amiloride, doxazosin, beta-blocker (bisoprolol/nebivolol); Step 4) Renal denervation (RDN) - SPYRAL HTN-OFF MED, RADIANCE-HTN; consider in true resistant HT after medical optimization; Step 5) Lifestyle - DASH diet, sodium <2.3 g/day, weight loss, exercise, alcohol restriction, sleep optimization.