What are the next steps for a patient with elevated blood pressure (hypertension) on lisinopril (ACE inhibitor) 20mg and amlodipine (calcium channel blocker) 10mg with readings of 138/91 and 124/84?

Blood Pressure Management: Adding a Third Agent

Add a thiazide or thiazide-like diuretic (chlorthalidone 12.5-25mg daily or hydrochlorothiazide 25-50mg daily) as your third antihypertensive agent, with chlorthalidone preferred due to its longer duration of action. 1, 2

Current Blood Pressure Assessment

Your patient's readings of 138/91 and 124/84 mmHg indicate:

• The systolic pressures are at or above the 130 mmHg threshold, and the diastolic reading of 91 mmHg exceeds the 90 mmHg target 1, 3
• While one reading (124/84) approaches goal, the other (138/91) represents persistent Grade 1 hypertension requiring treatment intensification 1
• The target should be <140/90 mmHg minimum, ideally <130/80 mmHg 1, 3

Rationale for Adding a Diuretic

Your patient is already on maximized doses of both lisinopril 20mg (standard maximum for hypertension per FDA labeling) and amlodipine 10mg (maximum dose) 4, 5. The guideline-recommended sequence for non-Black patients is: ACE inhibitor → add calcium channel blocker → optimize doses → add thiazide/thiazide-like diuretic 1, 2

• This three-drug combination targets different mechanisms: renin-angiotensin system blockade (lisinopril), vasodilation (amlodipine), and volume reduction (diuretic) 2, 6
• The combination of ACE inhibitor + calcium channel blocker + thiazide diuretic represents guideline-recommended triple therapy for uncontrolled hypertension 1, 2

Specific Diuretic Selection

Chlorthalidone 12.5-25mg daily is preferred over hydrochlorothiazide 25-50mg daily due to its longer duration of action 2, 6

• Both are acceptable options, but chlorthalidone provides more consistent 24-hour blood pressure control 2
• Start with the lower dose (chlorthalidone 12.5mg or HCTZ 25mg) to minimize electrolyte disturbances 2

Essential Monitoring After Adding Diuretic

Check serum potassium and creatinine 2-4 weeks after initiating diuretic therapy to detect potential hypokalemia or changes in renal function 1, 2

• Hypokalemia is the most common adverse effect of thiazide diuretics 2
• The combination of lisinopril (which tends to increase potassium) with a thiazide (which decreases potassium) often results in neutral potassium balance, but monitoring is still essential 4
• Reassess blood pressure within 2-4 weeks after adding the diuretic, with the goal of achieving target BP within 3 months 1, 2

Before Adding the Diuretic: Critical Steps

Verify medication adherence first, as non-adherence is the most common cause of apparent treatment resistance 2, 6

• Ask directly about missed doses, cost barriers, and side effects 6
• Consider pill counts or pharmacy refill records if adherence is uncertain 6

Confirm elevated readings with home blood pressure monitoring if not already done 1, 3

• Home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg confirms true hypertension 1
• This excludes white coat hypertension as a cause of elevated office readings 1

If Triple Therapy Fails: Fourth-Line Agent

If blood pressure remains uncontrolled after optimizing triple therapy (lisinopril + amlodipine + diuretic), add spironolactone 25-50mg daily as the preferred fourth-line agent for resistant hypertension 1, 2, 6

• Spironolactone has the strongest evidence for resistant hypertension, demonstrated in the PATHWAY-2 trial 6
• Monitor potassium closely when adding spironolactone to lisinopril, as hyperkalemia risk is significant with this combination 2, 4
• Alternative fourth-line agents if spironolactone is not tolerated or contraindicated include: amiloride, doxazosin, eplerenone, clonidine, or beta-blockers 1, 2, 6

Lifestyle Interventions: Non-Negotiable Additions

Reinforce sodium restriction to <2g/day, which can provide additive blood pressure reduction of 10-20 mmHg 2

• This is particularly important when adding a diuretic, as high sodium intake can blunt diuretic effectiveness 2
• Other lifestyle measures include maintaining healthy weight, regular exercise, and limiting alcohol 2

Important Caveats to Avoid

• Do not add a beta-blocker or other fourth agent before adding and optimizing a thiazide diuretic—this violates guideline-recommended stepwise approaches 1, 2
• Do not combine lisinopril with an ARB (like valsartan or losartan), as this increases adverse events without additional benefit 2
• Do not assume treatment failure without first confirming adherence and ruling out secondary causes of hypertension 1, 2, 6