What are the treatment options for resistant hypertension?

From the Guidelines

Resistant hypertension should be treated with a multi-faceted approach, including optimization of the current medication regimen and addition of low-dose spironolactone as the 4th line agent, if serum potassium is <4.5 mmol/L and eGFR is >45 ml/min/1.73m2, as recommended by the most recent guidelines 1. The treatment of resistant hypertension requires a comprehensive approach, starting with the exclusion of pseudoresistance and screening for secondary causes of hypertension, as outlined in the 2020 international society of hypertension global hypertension practice guidelines 1.

Key Considerations

• Optimization of the current treatment regimen, including health behavior change and diuretic-based treatment, with maximally tolerated doses of diuretics and optimal choice of diuretic 1.
• Addition of low-dose spironolactone as the 4th line agent, if serum potassium is <4.5 mmol/L and eGFR is >45 ml/min/1.73m2, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.
• Consideration of alternative agents, such as eplerenone, amiloride, beta-blockers, or alpha-blockers, if spironolactone is contraindicated or not tolerated 1.
• Referral to a hypertension specialist may be necessary to consider additional medications or device-based interventions, such as renal denervation, in select cases 1.

Lifestyle Modifications

• Sodium restriction to less than 2 grams daily
• Regular physical activity
• Weight loss if overweight
• Limiting alcohol consumption
• Following the DASH diet
• Home blood pressure monitoring to track progress and avoid white coat hypertension 1. The goal of treatment is to reduce cardiovascular risk by achieving blood pressure targets, typically less than 130/80 mmHg for most patients, 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. Treatment for Resistant Hypertension:

• Spironolactone can be used as add-on therapy to lower blood pressure in patients with resistant hypertension who are not adequately controlled on other agents 2.
• The goal is to lower blood pressure and reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
• Comprehensive cardiovascular risk management is recommended, including lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.

From the Research

Definition and Diagnosis of Resistant Hypertension

• Resistant hypertension is defined as blood pressure levels remaining elevated above target despite changes in lifestyle and concurrent use of at least three antihypertensive agents, including a long-acting calcium channel blocker (CCB), a blocker of the renin-angiotensin system (ACE inhibitor or angiotensin receptor blocker) and a diuretic 3, 4, 5, 6, 7.
• Diagnosis requires confirmation of blood pressure levels above target by out-of-office blood pressure measurements and exclusion of secondary causes of hypertension 3, 4, 5, 6, 7.

Lifestyle Changes and Management

• 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 3, 4, 5, 6, 7.
• Current treatment should be rationalised, including single pill combination treatment where antihypertensive drugs should be provided at the maximum tolerated dose 3.
• Current drugs should be replaced with a more appropriate and less difficult treatment regimen based on the patient's age, ethnicity, comorbidities, and risk of drug-drug interactions 3.

Treatment Options

• The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists such as spironolactone 3, 4, 5, 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, 4, 5, 6, 7.
• New approaches under research include selective non-steroidal mineralocorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin antagonist aprocitentan 3.

Refractory Hypertension

• Refractory hypertension is defined as uncontrolled blood pressure despite use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and an MR (mineralocorticoid receptor) antagonist, at maximal or maximally tolerated doses 5.
• Fluid retention, mediated largely by aldosterone excess, is the predominant mechanism underlying resistant hypertension, while patients with refractory hypertension typically exhibit increased sympathetic nervous system activity 5.