The following are key points to remember about this review on the diagnosis and management of resistant hypertension:

1. High blood pressure (hypertension) is one of the most important risk factors for cardiovascular diseases and is a significant cause of morbidity and mortality worldwide.
2. Resistant hypertension is generally defined as uncontrolled clinic blood pressure (>140/90 mm Hg) after treatment with three or more antihypertensives.
3. The National Institute for Health and Care Excellence (NICE) guidelines specify that these three antihypertensives should include optimal doses of an angiotensin-converting enzyme (ACE) inhibitor (or an angiotensin receptor blocker), a calcium channel blocker, and a diuretic.
4. Careful clinical examination of patients presenting with apparent resistant hypertension is required to avoid misdiagnosis due to pseudoresistant hypertension.
5. Pseudoresistant hypertension can be caused by poor clinic blood pressure measurement technique, patient nonadherence to prescribed medication, patient intolerance to certain antihypertensive medications, and white coat hypertension, and these causes need to be excluded.
6. The gold-standard measure of medication adherence is to take a urine sample after the patient has taken his or her medications and examine the sample for relevant drug metabolites using high-performance liquid chromatography-mass spectrometry.
7. Treatment of resistant hypertension is focused on the addition of fourth-line therapy where blood pressure is not controlled by treatment with three drugs, described by NICE as A+C+D: that is, an ACE inhibitor or an angiotensin II receptor blocker (A), a calcium channel antagonist (C), and a thiazide or thiazide-like diuretic (D).
8. Although the causes of resistant hypertension are poorly understood, accepted hypothesis is that it is caused by inappropriate sodium retention in the kidneys. For this reason, the NICE guidelines recommend spironolactone therapy as a fourth-line agent in patients with potassium of <4.5 mmol/L who are likely to respond to a mineralocorticoid receptor blocker. For patients with potassium of >4.5 mmol/L, it is recommended that the existing diuretic (thiazide or thiazide-like) be doubled.
9. For those patients who are intolerant to spironolactone, evidence-based treatment options are more limited, but other potassium-sparing diuretics can be tried (provided the potassium is <4.5 mmol/L) including amiloride or eplerenone; the latter acts in a similar way to spironolactone, but has less metabolic side effects.
10. At this time, the benefits of renal denervation, carotid baroreceptor stimulation, and central arteriovenous anastomosis remain inconclusive, and these procedures should not be adopted in routine clinical practice.

Keywords: Amiloride, Angiotensin Receptor Antagonists, Antihypertensive Agents, Angiotensin-Converting Enzyme Inhibitors, Arteriovenous Anastomosis, Blood Pressure, Calcium Channel Blockers, Chromatography, Liquid, Denervation, Diuretics, Hypertension, Mass Spectrometry, Medication Adherence, Metabolic Syndrome, Mineralocorticoid Receptor Antagonists, Primary Prevention, Risk Factors, Thiazides, Vascular Diseases, White Coat Hypertension

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