From the Guidelines
The evaluation and management of resistant hypertension should prioritize 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 diagnosis of resistant hypertension requires confirmation of true resistance by ensuring proper blood pressure measurement technique and medication adherence. True resistant hypertension is defined as blood pressure remaining above goal (typically >130/80 mmHg) despite concurrent use of three antihypertensive medications of different classes, including a diuretic, at optimal doses. Initial evaluation should include:
- A thorough medication review to identify interfering substances like NSAIDs, oral contraceptives, sympathomimetics, and certain herbal supplements
- Laboratory testing to assess for secondary causes, including comprehensive metabolic panel, thyroid function tests, plasma aldosterone-to-renin ratio, and 24-hour urine collection for metanephrines and cortisol if pheochromocytoma or Cushing's syndrome is suspected
- Imaging studies like renal ultrasound or CT angiography may be warranted to evaluate for renal artery stenosis or adrenal masses
- Home and ambulatory blood pressure monitoring to exclude white-coat hypertension Common secondary causes to consider include:
- Obstructive sleep apnea
- Primary aldosteronism
- Renal parenchymal disease
- Renal artery stenosis
- Pheochromocytoma Treatment optimization typically involves:
- Adding a mineralocorticoid receptor antagonist like spironolactone (25-50 mg daily) or eplerenone (50-100 mg daily)
- Ensuring diuretic therapy is appropriate for the patient's kidney function
- Considering specialized referral to a hypertension specialist if blood pressure remains uncontrolled despite these interventions, as suggested by the 2020 International Society of Hypertension global hypertension practice guidelines 2 and the 2018 American College of Cardiology/American Heart Association hypertension guideline 3.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Definition and Diagnosis of Resistant Hypertension
- Resistant hypertension is defined as blood pressure that remains 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 4, 5.
- It can also be diagnosed if blood pressure control requires four or more antihypertensive drugs 5.
- Diagnosis requires the exclusion of apparent treatment resistant hypertension, which is most often the result of non-adherence to treatment 5.
Prevalence of Resistant Hypertension
- The prevalence of true resistant hypertension in hypertension clinics is only about 11-13% 6.
- Higher prevalence rates are evident in populations with evidence of end-organ disease such as cardiac or renal disease where lower blood pressure targets have now been established 6.
Management of Resistant Hypertension
- Lifestyle changes 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 4.
- Current treatment should be rationalised, including single pill combination treatment where antihypertensive drugs should be provided at the maximum tolerated dose 4.
- The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists such as spironolactone 4, 5.
- Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine, and beta-blockers, as well as any other antihypertensive drugs not already in use 4.
Treatment Options
- Spironolactone has been shown to prevent chlorthalidone-induced sympathetic activation and insulin resistance in hypertensive patients 7.
- The addition of spironolactone to chlorthalidone has been shown to return sympathetic nerve activity to baseline and prevent insulin resistance 7.
- Doxazosin has also been shown to be effective in reducing blood pressure in patients with resistant hypertension, although the decrease in blood pressure was significantly greater with spironolactone 8.
New Approaches
- New approaches under research include selective non-steroidal mineralocorticoid receptor antagonists such as finerenone, esaxerenone, and ocedurenone, selective aldosterone synthase inhibitors such as baxdrostat, and dual endothelin antagonist aprocitentan 4.
- Device-based approaches such as renal denervation have also been tested and shown to be effective in reducing blood pressure in patients with resistant hypertension 5.