What are the treatment and evaluation options for resistant Hypertension (HTN)?

From the Guidelines

Resistant hypertension should be treated with reinforcement of lifestyle measures, especially sodium restriction, and the addition of low-dose spironolactone to existing treatment, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The treatment of resistant hypertension requires a comprehensive approach, including confirmation of true resistance, evaluation of secondary causes, and optimization of medication regimens.

Key Considerations

• Resistant hypertension is defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes, including a diuretic, at optimal doses.
• The 2024 ESC guidelines recommend the addition of low-dose spironolactone to existing treatment, or the addition of further diuretic therapy if intolerant to spironolactone, with either eplerenone, amiloride, a higher dose thiazide/thiazide-like diuretic, or a loop diuretic 1.
• Alternative fourth-line options include beta-blockers, such as bisoprolol, or alpha-blockers, such as doxazosin, as recommended by the 2024 ESC guidelines 1.

Lifestyle Modifications

• Sodium restriction (<2.3g daily) is essential in the management of resistant hypertension.
• Regular physical activity, weight loss if overweight, limiting alcohol consumption, and following the DASH diet are also crucial lifestyle modifications.

Medication Optimization

• Medication optimization should start with a regimen of an ACE inhibitor or ARB, a calcium channel blocker, and a thiazide diuretic.
• If blood pressure remains uncontrolled, the addition of a mineralocorticoid receptor antagonist, such as spironolactone, should be considered.

Evaluation and Referral

• Evaluation of secondary causes, such as primary aldosteronism, renal artery stenosis, chronic kidney disease, obstructive sleep apnea, and pheochromocytoma, is essential in the management of resistant hypertension.
• Referral to a hypertension specialist may be necessary if blood pressure remains uncontrolled despite optimal treatment.

From the FDA Drug Label

Spironolactone tablets are indicated as add-on therapy for the treatment of hypertension, to lower blood pressure in patients who are not adequately controlled on other agents. Many patients will require more than one drug to achieve blood pressure goals. The recommended initial daily dose is 25 mg to 100 mg of spironolactone tablets administered in either single or divided doses is recommended. Dosage can be titrated at two-week intervals. Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure.

For the treatment of resistant hypertension, spironolactone can be used as add-on therapy to lower blood pressure in patients who are not adequately controlled on other agents. The recommended initial daily dose is 25 mg to 100 mg, which can be titrated at two-week intervals.

• Key considerations for treatment include:
  • Starting with a low dose and titrating as needed
  • Monitoring blood pressure regularly to assess response to treatment
  • Adjusting the dose at two-week intervals to achieve optimal blood pressure control
  • Being aware that doses greater than 100 mg/day generally do not provide additional reductions in blood pressure 2
• Evaluation of resistant hypertension treatment with spironolactone should include regular monitoring of blood pressure and assessment of treatment response 2

From the Research

Definition and Diagnosis of Resistant Hypertension

• Resistant hypertension is defined as blood pressure above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different classes, including a diuretic, with all agents administered at maximum or maximally tolerated doses 3.
• It can also be diagnosed if blood pressure control requires four or more antihypertensive drugs 3.
• The diagnosis requires the exclusion of apparent treatment-resistant hypertension, which is most often the result of non-adherence to treatment 3.

Evaluation of Resistant Hypertension

• All patients with resistant hypertension should be evaluated for possible correctable factors associated with pseudoresistance, such as poor adherence, white coat hypertension, and suboptimal measurement of blood pressure 4.
• Evaluation should also include screening for secondary causes of hypertension, which account for less than 10% of cases of elevated blood pressure (BP) 5.
• Patients with resistant hypertension should undergo out-of-office blood pressure measurements to confirm blood pressure levels above target 6.

Treatment of Resistant Hypertension

• Lifestyle modifications, such as reduced sodium and alcohol intake, regular physical activity, weight loss, and discontinuation of substances that can interfere with blood pressure control, are recommended 6, 4.
• Antihypertensive medications typically include an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a long-acting thiazide-type/like diuretic 3.
• If a fourth drug is needed, evidence supports the addition of a mineralocorticoid receptor antagonist, such as spironolactone 6, 3.
• Alternative treatments, such as amiloride, doxazosin, eplerenone, clonidine, and beta-blockers, may also be considered 6.
• Novel interventional therapies, including renal denervation, baroreflex activation, and device-based options, may be used to lower blood pressure safely 7.

Management of Resistant Hypertension

• Patients with resistant hypertension require a thorough evaluation to confirm the diagnosis and optimize treatment, which typically includes a combination of lifestyle adjustments, pharmacologic, and interventional treatment 7.
• Combination therapy, including a diuretic, a long-acting calcium channel blocker, an angiotensin-converting enzyme inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist, is the classic regimen for patients with treatment-resistant hypertension 7.
• Mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, have been shown to be efficacious in patients with resistant hypertension, heart failure, chronic kidney disease, and primary aldosteronism 7.