Resistant arterial hypertension
Arterial hypertension where target BP is not achieved on three antihypertensive agents at maximally tolerated doses, one of which is a diuretic. Affects 10–15 % of hypertensive patients. ESC/ESH 2024 treats it as a separate clinical indication with its own recommendations: after adherence check and exclusion of secondary causes, a fourth agent is added – spironolactone or eplerenone.
ICD-10 I104 drugs
Also known as: Refractory hypertension, Resistant HTN
Drugs used for this condition
- ASpironolactoneFirst line · Potassium-sparing diuretics (mineralocorticoid receptor antagonists)First-line fourth agent for resistant hypertension. The PATHWAY-2 trial (Lancet 2015, 335 patients) demonstrated spironolactone 25–50 mg daily reduced home SBP by 8.7 mmHg more than placebo and significantly outperformed both doxazosin and bisoprolol. Subsequent meta-analyses replicated the effect. ESC/ESH 2024 lists spironolactone as a class I recommendation, level of evidence A. NICE NG136 and AHA/ACC 2017 support the same position.
- BChlortalidoneSecond line · Long-acting thiazide-like diureticIn resistant hypertension, swapping hydrochlorothiazide for chlorthalidone is one of the first moves, because a short-acting diuretic leaves the night and early morning uncovered. Chronic kidney disease raises a separate question: thiazides were long held to stop working below 30 ml/min of filtration. The CLICK trial (N Engl J Med 2021) tested that in 160 patients with stage 4 disease and poorly controlled blood pressure: chlorthalidone 12.5–50 mg over 12 weeks lowered 24-hour systolic pressure by about 11 mmHg more than placebo and reduced albuminuria. The price showed up in the same numbers: hypokalaemia, a reversible rise in creatinine, episodes of dizziness. The practical conclusion is that the drug works at reduced filtration but calls for electrolytes and creatinine every 2–4 weeks during titration.
- CAzilsartan medoxomil + chlorthalidoneAdd-on therapy · Fixed-dose combination: angiotensin II receptor blocker with a thiazide-like diureticIn resistant hypertension a sartan with a thiazide-like diuretic covers two of the three mandatory components of the regimen at once, leaving a calcium channel blocker to add. Chlorthalidone suits that role better than hydrochlorothiazide: a half-life of 40–60 hours holds the effect around the clock, and the CLICK trial (N Engl J Med 2021) showed it lowers blood pressure even in stage 4 chronic kidney disease, where thiazides were previously considered useless. The price of that duration is the same hypokalaemia, only stretched: the potassium drop shows up on day 5–14 rather than day two. The sartan in the combination absorbs part of that hit. One separate check in resistant hypertension is whether a second thiazide hides in another tablet of the regimen: indapamide next to this combination creates duplication with no gain in effect.
- CMoxonidineAdd-on therapy · Centrally acting antihypertensive, imidazoline I1 receptor agonistIn resistant hypertension, where blood pressure stays above target on three drugs including a diuretic, a fourth is added. The 2024 ESC guideline names spironolactone first for that slot and leaves centrally acting sympatholytics for cases where spironolactone did not work out because of hyperkalaemia, gynaecomastia or low renal filtration. Moxonidine does the job there, but its evidence base is a drop in blood pressure numbers rather than a drop in strokes. A practical point when a fourth drug goes in: moxonidine adds to any other antihypertensive by mechanism, and the first days after starting bring orthostatic hypotension, especially in older people. Standing blood pressure is measured separately from seated blood pressure.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit