What is the management approach for a 48-year-old patient with hypertension (high blood pressure) on losartan (Angiotensin II Receptor Antagonist) 100mg, doxazosin (Alpha-1 Adrenergic Receptor Antagonist) 2mg, amlodipine (Calcium Channel Blocker) 10mg, metoprolol (Beta-1 Selective Adrenergic Receptor Blocker) ER 25mg, and spironolactone (Mineralocorticoid Receptor Antagonist)-hydrochlorothiazide (HCTZ) (Thiazide Diuretic) 25-25, presenting with severely elevated blood pressure?

From the Guidelines

For this 48-year-old patient with uncontrolled hypertension despite being on five antihypertensive medications, I recommend optimizing the current treatment regimen and considering the addition of a low-dose spironolactone or further diuretic therapy, as the patient is already on spironolactone-HCTZ, but the dose of spironolactone may not be sufficient. The patient's blood pressure of 200/100 despite multiple medications suggests resistant hypertension, which requires more aggressive management 1. According to the 2024 ESC guidelines for the management of elevated blood pressure and hypertension, the recommended treatment of resistant hypertension includes reinforcement of lifestyle measures, especially sodium restriction, and the addition of low-dose spironolactone to existing treatment, or the addition of further diuretic therapy if intolerant to spironolactone 1. Some key points to consider in the management of this patient include:

• Optimizing the current treatment regimen, including health behavior change and diuretic-based treatment, with maximally tolerated doses of diuretics, and optimal choice of diuretic 1
• Evaluating the patient for secondary causes of hypertension, such as renal artery stenosis, primary aldosteronism, or obstructive sleep apnea
• Confirming medication adherence and advising the patient to monitor home blood pressure readings twice daily
• Emphasizing lifestyle modifications, including sodium restriction (<2g/day), regular exercise, weight management, and limiting alcohol intake, as these can significantly impact blood pressure control 1. The patient should be scheduled for follow-up within 2 weeks to reassess blood pressure control and consider referral to a specialist center if necessary. It is also important to note that the patient is already on a combination of medications, including losartan, doxazosin, amlodipine, metoprolol ER, and spironolactone-HCTZ, and any changes to the treatment regimen should be made with caution and close monitoring of the patient's blood pressure and overall health 1.

From the FDA Drug Label

The usual starting dose of losartan is 50 mg once daily. The dosage can be increased to a maximum dose of 100 mg once daily as needed to control blood pressure [see CLINICAL STUDIES (14.1)]. A starting dose of 25 mg is recommended for patients with possible intravascular depletion (e.g., on diuretic therapy).

The patient is already taking losartan 100mg, which is the maximum recommended dose. The patient's blood pressure is still high at 200/100, indicating that the current treatment regimen may not be sufficient to control their blood pressure.

• The patient is also taking other antihypertensive medications, including doxazin, amlodipine, metoprolol ER, and spironolactone-HCTZ.
• Considering the patient's current medication regimen and blood pressure reading, it may be necessary to re-evaluate and adjust their treatment plan to achieve better blood pressure control 2.

From the Research

Patient's Current Medication Regimen

The patient is currently taking:

• Losartan 100mg
• Doxazin 2mg
• Amlodipine 10mg
• Metoprolol ER 25mg
• Spironolactone-HCTZ 25-25mg

Blood Pressure Control

Despite being on multiple antihypertensive medications, the patient's blood pressure is still high at 200/100 mmHg. According to 3, the goal of treatment for high blood pressure is to reduce blood pressure to acceptable levels and improve cardiovascular risk status.

Multiple Drug Therapy

The use of multiple drug therapy in the treatment of essential hypertension is discussed in 3. It is stated that multiple drug therapy offers the possibility of greater therapeutic efficacy than single agents and can also reduce the incidence of side effects through complementary actions.

Quadruple Therapy

A systematic review of randomized controlled trials on the use of quadruple therapy in the management of hypertension is presented in 4. The results show that quadruple low-dose combination therapy is a promising approach for improving blood pressure control while maintaining a favorable safety profile.

Once-Daily Therapies

The benefits of once-daily therapies in the treatment of hypertension are discussed in 5. It is stated that once-daily agents with sustained therapeutic coverage can provide uniform 24-hour blood pressure control and improve patient adherence to treatment.

Beta-Blockers

The use of beta-blockers as first-line therapy for hypertension is controversial, as discussed in 6 and 7. The results of a meta-analysis presented in 6 suggest that atenolol may not be a suitable drug for hypertensive patients, and that it may be associated with higher mortality and cardiovascular morbidity compared to other antihypertensive treatments. A systematic review of randomized controlled trials on the use of beta-blockers as first-line therapy for hypertension is presented in 7, which suggests that beta-blockers may have inferior effects on mortality and cardiovascular disease compared to other antihypertensive drugs.

Potential Next Steps

Based on the evidence, potential next steps for the patient's treatment could include:

• Adjusting the current medication regimen to optimize blood pressure control
• Considering the use of quadruple therapy or once-daily therapies to improve treatment adherence and efficacy
• Re-evaluating the use of beta-blockers as part of the patient's treatment plan, given the potential for inferior effects on mortality and cardiovascular disease.