Resistant Hypertension

Background

• Resistant hypertension is defined as a hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg) despite the concurrent use of 3 antihypertensive drugs of different classes (including a diuretic), or controlled blood pressure with ≥ 4 antihypertensive drugs.
• Causes of or contributing factors to resistant hypertension include:
  • undiagnosed secondary hypertension
  • factors related to lifestyle and diet
  • suboptimal choice of antihypertensive regimen
  • certain medications
  • chronic kidney disease

Evaluation

• Exclude pseudoresistant hypertension (elevated blood pressure readings due to poor measurement technique, poor adherence, and/or white coat syndrome) and pseudohypertension (elevated blood pressure due to arterial stiffening in elderly patients).
• Evaluate patients for secondary causes of hypertension (Strong recommendation).
• Evaluate whether drugs included in a regimen have blood pressure-lowering effect and withdraw if the effect is minimal or absent (Strong recommendation).
• Evaluate whether or not concomitant medications have a blood pressure-raising effect, and withdraw if feasible.

Management

• Consider selected lifestyle modifications, such as weight loss, sodium restriction, and exercise.
• Medications
  • Most patients will require > 3 drugs; the initial 3-drug regimen generally consists of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a thiazide diuretic or thiazide-like diuretic.
  • Consider the sequential addition of the following medications (until blood pressure control is achieved) for patients with resistant hypertension who are not at blood pressure goal on 3-drug therapy:
    • Substitute previously used diuretic with a long-acting thiazide-like diuretic (such as indapamide or chlorthalidone) if estimated glomerular filtration rate (GFR) ≥ 30 mL/minute/1.73 m², or with loop diuretic if estimated GFR < 30 mL/minute/1.73 m².
    • Add mineralocorticoid receptor antagonist (spironolactone or eplerenone) if estimated GFR ≥ 30 mL/minute/1.73 m² and if hyperkalemia not present (Strong recommendation).
    • Add beta blocker (such as metoprolol succinate or bisoprolol), combined alpha/beta blocker (such as labetalol or carvedilol), alpha blocker (such as doxazosin), or central alpha agonist (such as clonidine patch or guanfacine).
    • Consider adding hydralazine (requires concomitant use of beta blocker and diuretic).
    • Consider substituting minoxidil for hydralazine (requires concomitant use of beta blocker and loop diuretic).
• Invasive procedures (such as renal denervation or baroreceptor stimulation) should not be used for routine hypertension treatment until additional evidence for efficacy and safety becomes available (Strong recommendation).