What is the initial approach to managing resistant hypertension?

From the Guidelines

The initial approach to managing resistant hypertension involves confirming true resistance and optimizing the current antihypertensive regimen, with the addition of low-dose spironolactone as a fourth-line agent being a key recommendation, as stated in the 2024 ESC guidelines 1. The management of resistant hypertension requires a comprehensive approach that addresses the multifactorial nature of the condition. This includes:

• Confirming true resistance by ensuring proper blood pressure measurement technique, medication adherence, and ruling out white coat hypertension through ambulatory monitoring.
• Optimizing the current antihypertensive regimen, typically including a thiazide diuretic, an ACE inhibitor or ARB, and a calcium channel blocker at maximally tolerated doses.
• Adding a fourth agent, typically spironolactone 25-50mg daily, which has shown superior efficacy as a fourth-line agent, as recommended by the 2024 ESC guidelines 1 and supported by other studies 1.
• Lifestyle modifications, including sodium restriction, regular physical activity, weight loss if overweight, limiting alcohol consumption, and following the DASH diet.
• Evaluating secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, renal artery stenosis, and chronic kidney disease.
• Medication review to identify drugs that may contribute to hypertension, such as NSAIDs, certain antidepressants, and oral contraceptives. The 2024 ESC guidelines 1 provide the most recent and highest-quality evidence for the management of resistant hypertension, and their recommendations should be prioritized in clinical practice.

From the FDA Drug Label

DOSAGE & ADMINISTRATION 2. 1 Hypertension Initial Therapy in adults: The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 mg to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give greater effect Use with diuretics in adults If blood pressure is not controlled with lisinopril tablets alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12. 5 mg). Therapy should be initiated with the lowest possible dose. This dose should be titrated according to individual patient response to gain maximal therapeutic benefit while maintaining lowest dosage possible. The usual initial dose of Furosemide tablets is 20 to 80 mg given as a single dose. Ordinarily a prompt diuresis ensues If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased.

The initial approach to managing resistant hypertension involves:

• Starting with the lowest possible dose of an antihypertensive medication, such as lisinopril or chlorthalidone.
• Titration of the dose according to individual patient response to gain maximal therapeutic benefit while maintaining the lowest dosage possible.
• Consideration of adding a diuretic, such as hydrochlorothiazide or furosemide, if blood pressure is not controlled with the initial medication alone.
• Careful monitoring of blood pressure and adjustment of the dosage as needed to achieve the desired therapeutic response.
• Potential use of combination therapy with multiple antihypertensive agents to achieve adequate blood pressure control 2, 3, 4.

From the Research

Definition and Diagnosis of Resistant Hypertension

• Resistant hypertension is defined as an uncontrolled office blood pressure (BP) despite the use of at least three antihypertensive drugs 5.
• It is also defined as blood pressure above the patient's goal despite the use of 3 or more antihypertensive agents from different classes at optimal doses, one of which should ideally be a diuretic 6.
• The initial diagnostic approach involves drug adherence checking and the evaluation of antihypertensive scheme, emphasizing the use of diuretics and adequate combination and dosages of the two other drugs 5.

Initial Approach to Managing Resistant Hypertension

• The initial approach to managing resistant hypertension involves lifestyle changes and use of adequate combinations of antihypertensive agents from different classes 5.
• It is recommended to rationalise current treatment, including single pill combination treatment where antihypertensive drugs should be provided at the maximum tolerated dose 7.
• The treatment should be tailored to the patient's profile and focus on the causative pathway of resistance 6.
• Ambulatory BP monitoring (ABPM) at baseline is mandatory to classify patients into true RH (uncontrolled ambulatory BPs) and white-coat RH (controlled ambulatory BPs), and define initial therapeutic approach 5.

Pharmacological Treatment

• Pharmacological treatment should include a diuretic, and the use of adequate combinations of antihypertensive agents from different classes 5, 6.
• The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists such as spironolactone 7.
• Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine and beta-blockers, as well as any other antihypertensive drugs not already in use 7.

Lifestyle Changes

• 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 7.
• Maximizing lifestyle modification is also an important part of the management of resistant hypertension 8.