What is the initial treatment approach for patients with resistant hypertension?

From the Guidelines

The initial treatment approach for resistant hypertension involves optimizing the current medication regimen and adding a fourth agent, typically spironolactone, to achieve blood pressure control. According to the most recent guidelines, such as the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1, the treatment of resistant hypertension should focus on optimizing the current treatment regimen, including health behavior change and diuretic-based treatment. This includes ensuring patients are on maximum tolerated doses of three different antihypertensive drug classes, including a diuretic. If blood pressure remains uncontrolled, the addition of spironolactone should be considered, as it has shown superior efficacy as a fourth-line agent 1.

Some key points to consider in the treatment of resistant hypertension include:

• Optimizing the current medication regimen by ensuring patients are on maximum tolerated doses of three different antihypertensive drug classes, including a diuretic
• Adding a fourth agent, typically spironolactone, to achieve blood pressure control
• Addressing potential causes of pseudo-resistance, such as poor medication adherence, white coat hypertension, and improper blood pressure measurement technique
• Emphasizing lifestyle modifications, including sodium restriction, regular physical activity, weight loss if overweight, limiting alcohol consumption, and following the DASH diet
• Investigating secondary causes of hypertension, such as primary aldosteronism, renal artery stenosis, obstructive sleep apnea, and chronic kidney disease, particularly in patients with suggestive clinical features

It's essential to note that the treatment of resistant hypertension should be individualized and based on the patient's specific needs and clinical characteristics. The 2020 International Society of Hypertension Global Hypertension Practice Guidelines also recommend optimizing the current treatment regimen and adding a fourth agent, such as spironolactone, to achieve blood pressure control 1. Overall, the goal of treatment is to achieve blood pressure control and reduce the risk of cardiovascular complications, while also improving the patient's quality of life.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Therapy should be initiated with the lowest possible dose. A single dose given in the morning with food is recommended; Hypertension Initiation Therapy, in most patients, should be initiated with a single daily dose of 25 mg. If the response is insufficient after a suitable trial, the dosage may be increased to a single daily dose of 50 mg. If additional control is required, the dosage of chlorthalidone may be increased to 100 mg once daily or a second antihypertensive drug (step 2 therapy) may be added

The initial treatment approach for patients with resistant hypertension is not directly addressed in the provided drug labels.

• The labels provide information on the treatment of hypertension and edema, but do not specifically mention resistant hypertension.
• The treatment approach for hypertension is to initiate therapy with a single daily dose of 25 mg of chlorthalidone and adjust as needed, or to use spironolactone at a recommended initial daily dose of 25 mg to 100 mg.
• However, without direct information on resistant hypertension, no conclusion can be drawn about the initial treatment approach for this specific condition 2 3.

From the Research

Initial Treatment Approach for Resistant Hypertension

The initial treatment approach for patients with resistant hypertension involves a combination of lifestyle modifications and pharmacological interventions.

• Lifestyle modifications include reduced sodium and alcohol intake, regular physical activity, weight loss, and discontinuation of substances that can interfere with blood pressure control 4.
• Pharmacological interventions typically involve the use of at least three antihypertensive agents at optimal doses, including a diuretic, with consideration of a mineralocorticoid receptor antagonist as a fourth agent 5, 4, 6.

Evaluation and Diagnosis

Evaluation of suspected resistant hypertension starts with confirming adherence to the drug regimen and ruling out white coat hypertension using out-of-office blood pressure level measurements 6.

• Patients with resistant hypertension should be evaluated for possible correctable factors associated with pseudoresistance, such as poor adherence and suboptimal measurement of blood pressure 5.
• Secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, and renovascular disease, should also be considered 7, 8.

Treatment Options

Treatment options for resistant hypertension include:

• Thiazide diuretics as one of the first agents, in addition to mineralocorticoid receptor antagonists 5.
• A dihydropyridine calcium channel blocker and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, in addition to a diuretic 6.
• Spironolactone as an effective fourth drug, with alternatives including amiloride, doxazosin, eplerenone, clonidine, and beta-blockers 4, 6.
• Newer interventional therapies, such as renal denervation and baroreflex activation, may also be considered 5, 8.