What is the next step in managing a patient with uncontrolled hypertension (elevated blood pressure) on amlodipine (calcium channel blocker) 10 mg and lisinopril (angiotensin-converting enzyme inhibitor) 40 mg daily?

Management of Uncontrolled Hypertension on Amlodipine and Lisinopril

The next step in managing this patient with uncontrolled hypertension (156/78 mmHg) on maximum doses of amlodipine 10 mg and lisinopril 40 mg daily should be the addition of a thiazide-like diuretic such as indapamide 2.5 mg daily. 1

Assessment of Current Therapy

• The patient is already on maximum doses of two first-line antihypertensive medications from different classes (ACE inhibitor and calcium channel blocker) but has not achieved target blood pressure 1
• Current combination therapy with amlodipine (calcium channel blocker) and lisinopril (ACE inhibitor) is appropriate as a foundation for hypertension treatment, but clearly insufficient in this case 1
• The systolic blood pressure of 156 mmHg remains significantly above the recommended target range of 120-129 mmHg 1

Recommended Next Steps

Add a Thiazide/Thiazide-like Diuretic

• When a two-drug combination fails to control blood pressure, increasing to a three-drug combination is recommended, typically adding a thiazide/thiazide-like diuretic to the RAS blocker and calcium channel blocker 1
• The 2020 International Society of Hypertension guidelines specifically recommend adding a thiazide/thiazide-like diuretic as the third agent when blood pressure is not controlled with an ACE inhibitor/ARB and calcium channel blocker 1
• Research evidence supports that adding a thiazide diuretic to the combination of amlodipine and lisinopril provides a significantly greater reduction in blood pressure compared to adding a beta-blocker 2

Specific Diuretic Recommendation

• Indapamide 2.5 mg daily is an appropriate thiazide-like diuretic option as recommended in treatment algorithms for resistant hypertension 1
• Chlorthalidone is another effective thiazide-like diuretic option that has shown superior outcomes in clinical trials 1
• Consider starting at a low dose and titrating up if needed to minimize metabolic side effects 1

Management Algorithm for Resistant Hypertension

1. Verify adherence to current medications - Ensure the patient is actually taking both amlodipine and lisinopril as prescribed 1

2. Add thiazide-like diuretic - Add indapamide 2.5 mg daily or chlorthalidone 12.5-25 mg daily 1

3. Monitor response after 2-4 weeks - Assess blood pressure control and tolerance of the three-drug regimen 1

4. If blood pressure remains uncontrolled:

   • Consider adding spironolactone 25-50 mg daily as a fourth agent, particularly effective in resistant hypertension 1
   • Alternative fourth-line options if spironolactone is not tolerated include eplerenone, amiloride, doxazosin, or a beta-blocker 1

5. Consider referral to hypertension specialist if blood pressure remains ≥160/100 mmHg despite treatment with ≥3 drugs or if there are multiple drug intolerances 1

Important Considerations

• Fixed-dose single-pill combinations should be used whenever possible to improve adherence 1
• Monitor electrolytes and renal function after adding a diuretic, particularly given concurrent ACE inhibitor therapy 3
• Lisinopril attenuates potassium loss caused by thiazide diuretics, but the combination requires monitoring of serum potassium 3
• Evaluate for potential secondary causes of hypertension if blood pressure remains difficult to control despite appropriate triple therapy 1

Drug Interactions and Precautions

• When adding a thiazide diuretic to lisinopril, be aware that lisinopril attenuates potassium loss caused by thiazide diuretics 3
• Avoid NSAIDs which may attenuate the antihypertensive effect of ACE inhibitors and can worsen renal function 3
• Never combine another RAS blocker (such as an ARB) with lisinopril as dual RAS blockade increases risks of hypotension, hyperkalemia, and renal dysfunction 3