What is the initial approach to managing refractory hypertension (high blood pressure that is difficult to control)?

From the Guidelines

The initial approach to managing refractory hypertension involves a comprehensive evaluation to identify underlying causes and optimize the treatment regimen, as recommended by the 2020 international society of hypertension global hypertension practice guidelines 1.

Key Steps in Managing Refractory Hypertension

• Ensure the patient is truly refractory by confirming medication adherence, proper blood pressure measurement technique, and ruling out white coat hypertension through ambulatory monitoring.
• Optimize the current treatment regimen including health behavior change and diuretic-based treatment, with maximally tolerated doses of diuretics, and optimal choice of diuretic.
• Consider screening patients for secondary causes as appropriate, such as obstructive sleep apnea, primary aldosteronism, renal artery stenosis, and chronic kidney disease.
• Add a low dose of spironolactone as the 4th line agent in those whose serum potassium is <4.5 mmol/L and whose eGFR is >45 ml/min/1.73m2 to achieve BP targets, as supported by the 2020 guidelines 1.

Lifestyle Modifications

• Sodium restriction to less than 2g daily
• Regular physical activity
• Weight management
• Limited alcohol consumption
• A DASH diet

Additional Considerations

• Resistant hypertension should be managed in specialist centers with sufficient expertise, and resources necessary to diagnose and treat this condition, as recommended by the 2020 guidelines 1.
• The use of loop diuretics in patients with CKD, and referral to a hypertension specialist if BP remains uncontrolled, are also important considerations in managing refractory hypertension, as noted in the 2018 American College of Cardiology/American Heart Association hypertension guideline 1.

From the FDA Drug Label

1.2 Hypertension 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. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC)

The initial approach to managing refractory hypertension involves using spironolactone as add-on therapy to lower blood pressure in patients who are not adequately controlled on other agents.

• The treatment should be guided by published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) 2.
• Control of high blood pressure should be part of comprehensive cardiovascular risk management.
• It is recommended to follow the guidelines for specific advice on goals and management.
• Many patients will require more than one drug to achieve blood pressure goals.

From the Research

Initial Approach to Refractory Hypertension

The initial approach to managing refractory hypertension involves a thorough evaluation to confirm the diagnosis and optimize treatment. This includes:

• Checking drug adherence and evaluating the antihypertensive scheme, emphasizing the use of diuretics and adequate combination and dosages of other drugs 3
• Ambulatory blood pressure monitoring (ABPM) at baseline to classify patients into true refractory hypertension (uncontrolled ambulatory BPs) and white-coat refractory hypertension (controlled ambulatory BPs) 3
• Lifestyle changes and use of adequate combinations of antihypertensive agents from different classes 3, 4

Diagnostic Evaluation

The diagnostic evaluation of refractory hypertension includes:

• Excluding medication nonadherence and the white coat effect 4
• Evaluating for secondary causes of hypertension, such as obstructive sleep apnea, primary aldosteronism, renovascular disease, and chronic kidney disease 5, 6
• Assessing for metabolic abnormalities and end-organ damage 5, 6

Treatment Options

Treatment options for refractory hypertension include:

• Combination therapy with a diuretic, a long-acting calcium channel blocker, an angiotensin-converting enzyme inhibitor, a beta blocker, and a mineralocorticoid receptor antagonist 5
• Addition of spironolactone or amiloride to the standard 3-drug antihypertensive regimen 4
• Novel interventional therapies, such as baroreflex activation and renal denervation, for patients who have failed other treatments 5

Special Considerations

Special considerations in the management of refractory hypertension include:

• Factitious hypertension, which is a rare cause of resistant or refractory hypertension, and should be suspected in patients with a history of visits to multiple institutions and physicians, negative secondary workup, absence of overt target organ damage, history of psychiatric illness, and employment in the medical field 7
• Referral to a hypertension specialist for patients with refractory hypertension who have failed to achieve control despite optimal treatment 6