What is the first-line treatment option for Resistant Hypertension?

From the Guidelines

The first-line treatment option for resistant hypertension is 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. Resistant hypertension is defined as blood pressure that remains above goal despite the concurrent use of three antihypertensive agents of different classes, including a diuretic, at optimal doses. Before adding spironolactone, it's essential to confirm true resistance by ruling out medication non-adherence, white coat hypertension, and secondary causes of hypertension.

Key Considerations

• Spironolactone works as an aldosterone antagonist, blocking mineralocorticoid receptors and promoting sodium and water excretion while retaining potassium.
• This mechanism is particularly effective in resistant hypertension, which often involves aldosterone excess or sensitivity.
• When initiating spironolactone, monitor serum potassium and renal function after 1-2 weeks, especially in patients with chronic kidney disease or diabetes.
• If spironolactone is not tolerated due to side effects like gynecomastia in men, eplerenone can be substituted, as suggested by the 2020 International Society of Hypertension global hypertension practice guidelines 1.

Alternative Options

• Alternative add-on agents if mineralocorticoid receptor antagonists are contraindicated include beta-blockers, alpha-blockers like doxazosin, or further diuretic therapy, though these are generally less effective than spironolactone for resistant hypertension.
• 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, as recommended by the 2024 ESC guidelines 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.

The first-line treatment option for Resistant Hypertension is not specified in the drug label.

• Add-on therapy is mentioned, implying that spironolactone is used in conjunction with other therapies, but the label does not provide information on the initial treatment approach for resistant hypertension. 2

From the Research

First-Line Treatment Options for Resistant Hypertension

The first-line treatment for resistant hypertension involves a combination of lifestyle changes and medication management.

• Lifestyle changes include reduced sodium and alcohol intake, regular physical activity, weight loss, and discontinuation of substances that can interfere with blood pressure control 3.
• Medication management typically begins with optimizing the current treatment regimen, including the use of single pill combination treatment and ensuring that antihypertensive drugs are provided at the maximum tolerated dose 3.
• The initial medication regimen usually includes a diuretic, a blocker of the renin-angiotensin system, and a calcium channel blocker 4, 3.
• It is essential to identify and address contributors to resistant hypertension, such as medication adherence, lifestyle factors, and the use of interfering substances 4.

Key Considerations for Treatment

• Evaluation for secondary causes of hypertension, such as sleep apnea, primary aldosteronism, chronic kidney disease, or renovascular disease, may be indicated 4, 5.
• Inadequate dosing, lack of using long-acting diuretics, and suboptimal combinations are common causes of resistant hypertension 4.
• Appropriate pharmacotherapy begins with ensuring the patient is receiving appropriate therapy for compelling indications, as outlined by the JNC-7 guidelines 4.
• Specific regimen enhancements to achieve blood pressure control include the addition of aldosterone antagonists, dual renin-angiotensin system blockade, and dual calcium channel blockade 4.

Additional Treatment Options

• If a fourth antihypertensive drug is needed to control blood pressure, a mineralocorticoid receptor antagonist, such as spironolactone, should be added to the therapeutic regimen 6, 7.
• Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine, and beta-blockers, as well as any other antihypertensive drugs not already in use 3.
• New approaches under research include selective non-steroidal mineralocorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin antagonists 3.