From the Guidelines
For uncontrolled hypertension in a patient already on amlodipine, lisinopril, and metoprolol, adding low-dose spironolactone to existing treatment is the most appropriate next step. This recommendation is based on the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The guidelines suggest that in patients with resistant hypertension and uncontrolled BP despite use of first-line BP-lowering therapies, the addition of spironolactone to existing treatment should be considered.
Key Considerations
- Spironolactone is particularly effective in resistant hypertension and can be added at a low dose to the existing treatment regimen.
- If the patient is intolerant to spironolactone, further diuretic therapy can be considered, including eplerenone, amiloride, a higher dose thiazide/thiazide-like diuretic, or a loop diuretic 1.
- It is essential to monitor electrolytes, especially potassium, within 1-2 weeks of initiation, as combining ACE inhibitors like lisinopril with certain diuretics can affect potassium levels.
- The addition of spironolactone targets the aldosterone pathway, complementing the calcium channel blocker (amlodipine), ACE inhibitor (lisinopril), and beta-blocker (metoprolol) already prescribed.
Alternative Options
- If spironolactone is not effective or tolerated, treatment with eplerenone instead of spironolactone, or the addition of a beta-blocker if not already indicated, and, next, a centrally acting BP-lowering medication, an alpha-blocker, or hydralazine, or a potassium-sparing diuretic should be considered 1.
- Catheter-based renal denervation may be considered for resistant hypertension patients who have BP that is uncontrolled despite a three BP-lowering drug combination, and who express a preference to undergo renal denervation after a shared risk-benefit discussion and multidisciplinary assessment 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. The medication that can be added for uncontrolled hypertension in a patient already on amlodipine, lisinopril, and metoprolol is spironolactone, as it is indicated for use as add-on therapy to lower blood pressure in patients not adequately controlled on other agents 2.
- Key points:
- Spironolactone can be used as add-on therapy for hypertension.
- It is indicated for patients not adequately controlled on other agents.
- The goal is to lower blood pressure and reduce the risk of cardiovascular events.
From the Research
Medication Options for Uncontrolled Hypertension
The following medications can be considered for addition to a patient's regimen already including amlodipine (calcium channel blocker), lisinopril (angiotensin-converting enzyme inhibitor), and metoprolol (beta blocker):
- A diuretic, such as chlorthalidone or hydrochlorothiazide, as evidenced by studies 3, 4, 5
- An aldosterone antagonist, as suggested by research 5
- A different angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, although ACEIs and ARBs should not be used simultaneously 6
- Other calcium channel blockers, if not already at maximum dose, considering the patient is already on amlodipine 7
Considerations for Combination Therapy
When selecting additional medications, consider the following:
- In black patients, include a thiazide diuretic or a calcium channel blocker 6
- For patients with heart failure with reduced ejection fraction, consider a beta blocker and an ACEI or ARB, followed by add-on therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status 6
- For patients with chronic kidney disease and proteinuria, include an ACEI or ARB plus a thiazide diuretic or a calcium channel blocker 6
- For patients with diabetes mellitus, treat similarly to those without diabetes unless proteinuria is present, in which case combination therapy should include an ACEI or ARB 6