What is the diagnosis and treatment of resistant hypertension?

From the Guidelines

Resistant hypertension should be managed 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.

Key Considerations

• The management of resistant hypertension involves a multi-faceted approach, including lifestyle modifications and medication optimization.
• The preferred regimen includes a long-acting thiazide diuretic, an ACE inhibitor or ARB, and a calcium channel blocker.
• If blood pressure remains uncontrolled, adding a mineralocorticoid receptor antagonist like spironolactone is often effective as a fourth agent.
• Other options include beta-blockers, alpha-blockers, or direct vasodilators.

Lifestyle Modifications

• Sodium restriction (<2g/day) is essential in managing resistant hypertension.
• Weight loss, regular exercise, limited alcohol consumption, and a DASH diet are also recommended.

Medication Optimization

• The addition of low-dose spironolactone to existing treatment is recommended for patients with resistant hypertension 1.
• Other options include the addition of further diuretic therapy, such as eplerenone, amiloride, a higher dose thiazide/thiazide-like diuretic, or a loop diuretic.
• Beta-blockers, such as bisoprolol, or alpha-blockers, such as doxazosin, may also be considered.

Secondary Causes

• Medication adherence should be verified, and secondary causes such as obstructive sleep apnea, primary aldosteronism, renal artery stenosis, or pheochromocytoma should be investigated.
• The pathophysiology of resistant hypertension often involves increased sympathetic nervous system activity, sodium retention, and vascular remodeling, which explains why multiple medication classes targeting different mechanisms are necessary for effective control.

Specialist Referral

• Resistant hypertension should be managed in specialist centers with sufficient expertise and resources necessary to diagnose and treat this condition 1.
• Catheter-based renal denervation may be considered for resistant hypertension patients who have BP that is uncontrolled despite a three BP-lowering drug combination, and who express a preference to undergo renal denervation after a shared risk-benefit discussion and multidisciplinary assessment 1.

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.

Resistant Hypertension can be managed with spironolactone as add-on therapy to lower blood pressure in patients not adequately controlled on other agents.

• The goal is to achieve blood pressure goals, and many patients may require more than one drug to do so.
• Spironolactone is indicated for this purpose, as stated in the drug label 2.

From the Research

Definition and Diagnosis of Resistant Hypertension

• Resistant hypertension (RH) is defined as blood pressure that remains above target levels despite the use of at least three antihypertensive drugs, including a diuretic, at optimal doses 3, 4, 5, 6, 7.
• The diagnosis of RH requires the exclusion of non-adherence, "white coat effect", and incorrect blood pressure measurement 3, 5, 7.
• Out-of-office blood pressure measurements, such as 24-hour ambulatory blood pressure monitoring, should be used to confirm the diagnosis of RH 5, 6.

Treatment of Resistant Hypertension

• Lifestyle modifications, such as low dietary salt intake, regular physical activity, and weight loss, are recommended for all patients with RH 3, 5, 6, 7.
• The treatment of RH typically involves the use of a combination of antihypertensive drugs, including a diuretic, a calcium channel blocker, and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker 3, 4, 5, 6.
• Mineralocorticoid receptor antagonists, such as spironolactone, are often used as a fourth-line treatment for RH 4, 6.
• Other treatment options for RH include beta blockers, long-acting nondihydropyridine calcium channel blockers, and clonidine or guanfacine 5, 6.
• Newer interventional therapies, such as renal denervation, are also being explored as treatment options for RH 4, 7.

Secondary Causes of Resistant Hypertension

• Secondary causes of RH, such as endocrine disorders and renal disease, should be evaluated and treated accordingly 3, 6.
• Primary hyperaldosteronism is a common secondary cause of RH, and its management is critical for controlling blood pressure 3.
• Other secondary causes of RH include phaeochromocytoma, hypercortisolism, and sleep apnea disorders 3, 5.