Should I continue to increase lisinopril (angiotensin-converting enzyme inhibitor) in a patient with uncontrolled hypertension (high blood pressure) in the evenings, despite current medication regimen of lisinopril, amlodipine (calcium channel blocker), and carvedilol (beta blocker)?

Evening Hypertension Management: Add a Thiazide-Like Diuretic, Not More Lisinopril

Instead of continuing to increase lisinopril, you should add a thiazide-like diuretic (preferably chlorthalidone or indapamide) as your next step, and consider moving one of your morning medications to bedtime dosing. Your patient is now on triple therapy without a diuretic, which represents suboptimal resistant hypertension management according to current guidelines 1.

Why Not Increase Lisinopril Further

• Lisinopril 20 mg daily is already at the mid-to-high therapeutic range, and further dose escalation without adding a diuretic contradicts the stepwise approach recommended by major hypertension guidelines 1, 2.
• The International Society of Hypertension guidelines clearly specify that after optimizing ACE inhibitor/ARB and calcium channel blocker doses, the next step is adding a thiazide-like diuretic, not further ACE inhibitor dose increases 1.
• Your patient has ACE inhibitor + calcium channel blocker + beta-blocker but is missing the critical diuretic component that should be part of any three-drug regimen for resistant hypertension 1.

Recommended Next Steps

Add a Thiazide-Like Diuretic (Fourth Agent)

• Add chlorthalidone 12.5-25 mg daily or indapamide 1.25-2.5 mg daily as these thiazide-like diuretics have superior cardiovascular outcomes compared to hydrochlorothiazide 1.
• Chlorthalidone provides an additional 7-8 mmHg systolic BP reduction compared to hydrochlorothiazide at equivalent doses 1.
• The American Heart Association guidelines for resistant hypertension specifically recommend thiazide-like diuretics as the third agent before considering a fourth medication class 1.

Consider Bedtime Dosing Strategy

• Move either the lisinopril or amlodipine to bedtime to address the evening BP elevation 1, 3.
• Research shows that bedtime dosing of at least one antihypertensive medication significantly reduces asleep BP and improves the nocturnal dipping pattern in resistant hypertension patients 3.
• Patients taking medications at bedtime had 54.4% prevalence of non-dipping compared to 80.5% in those taking all medications in the morning 3.
• However, note that recent diabetes guidelines suggest preferential bedtime dosing is not universally recommended, so this should be individualized based on your patient's specific BP pattern 1.

If Still Uncontrolled: Add Spironolactone (Fifth Agent)

• If BP remains elevated after adding a diuretic, add spironolactone 12.5-25 mg daily as the most effective fourth-line agent for resistant hypertension 1.
• Mineralocorticoid receptor antagonists are more effective than alpha- or beta-blockers for resistant hypertension when added to ACE inhibitor/ARB + calcium channel blocker + diuretic 1.
• Approximately 70% of resistant hypertension patients are candidates for spironolactone based on kidney function (eGFR ≥45 mL/min/1.73m²) and potassium levels (≤4.5 mEq/L) 1.

Critical Monitoring Requirements

• Check serum creatinine and potassium within 1-2 weeks after adding a diuretic, and again after adding spironolactone if needed 1.
• Monitor for hyperkalemia risk, especially when combining ACE inhibitors with spironolactone 1.
• Confirm true resistant hypertension with home BP monitoring or 24-hour ambulatory BP monitoring to exclude white coat effect 1.

Important Caveats

• Verify medication adherence first before escalating therapy, as non-adherence is a common cause of apparent resistant hypertension 1.
• Consider secondary hypertension causes if BP remains uncontrolled despite optimal four-drug therapy 1.
• The carvedilol (beta-blocker) in your patient's regimen is appropriate given it's already prescribed, but beta-blockers are not first-line for hypertension alone and are typically reserved as fifth-line agents unless there's a specific indication like heart failure or prior MI 1.