What other antihypertensive medications can be added to a regimen of lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor), amlodipine (Calcium Channel Blocker (CCB)), and furosemide (Lasix, Loop Diuretic) for uncontrolled blood pressure?

Adding to a Regimen of Lisinopril, Amlodipine, and Furosemide for Uncontrolled Hypertension

For uncontrolled hypertension on lisinopril, amlodipine, and furosemide, adding a mineralocorticoid receptor antagonist like spironolactone is the most effective next step. 1

Current Medication Analysis

Your current regimen includes:

• Lisinopril (ACE inhibitor)
• Amlodipine (Calcium Channel Blocker)
• Furosemide (Loop Diuretic)

This combination already covers three major antihypertensive classes, but persistent uncontrolled blood pressure indicates resistant hypertension.

Recommended Next Addition

First Choice: Mineralocorticoid Receptor Antagonist

• Spironolactone (12.5-50 mg daily) is the preferred option for resistant hypertension
• Studies show spironolactone can lower blood pressure by an additional 25/12 mmHg when added to existing multidrug regimens 1
• This effect is consistent across both African American and white patients
• The blood pressure response is not predicted by baseline plasma aldosterone or renin activity

Alternative Option: Thiazide or Thiazide-like Diuretic

If you're not already on a thiazide diuretic (since you're on furosemide):

• Consider switching from furosemide to a thiazide diuretic (chlorthalidone 12.5-25 mg or hydrochlorothiazide 25-50 mg) 1, 2
• Thiazide diuretics have shown superior outcomes in preventing cardiovascular events compared to other classes 2

Medication Combinations to Avoid

• Do not add another ACE inhibitor or ARB to your current regimen with lisinopril
• Dual RAS blockade (combining ACE inhibitors with ARBs) is explicitly advised against by all guidelines due to increased risk of kidney injury and stroke 1
• Beta-blockers combined with thiazide diuretics may increase diabetes risk 1

Resistant Hypertension Considerations

If blood pressure remains uncontrolled after adding a fourth medication:

1. Ensure medication adherence
2. Consider evaluation for secondary causes of hypertension
3. Optimize dosing of all medications
4. Consider consultation with a hypertension specialist

Dosing Strategy

For optimal blood pressure control:

• Start the new medication at a low dose (spironolactone 12.5 mg daily)
• Titrate up every 2-4 weeks until blood pressure control is achieved 1
• Maximum recommended dose of spironolactone for hypertension is 50 mg daily
• Monitor potassium levels closely when adding spironolactone to an ACE inhibitor

Special Considerations

• If you have chronic kidney disease, monitor renal function and potassium levels more frequently
• If you're over 65 years old, start with lower doses and titrate more gradually
• If you have diabetes, maintain a target blood pressure of <130/80 mmHg 3

Monitoring Recommendations

• Check blood pressure, renal function, and electrolytes 2-4 weeks after starting the new medication
• Monitor for side effects specific to spironolactone (gynecomastia, hyperkalemia)
• Continue lifestyle modifications including sodium restriction, weight management, and regular physical activity

Adding spironolactone to your current three-drug regimen represents the most evidence-based approach for managing resistant hypertension and improving cardiovascular outcomes.