What adjustments should be made to the medication regimen of an elderly gentleman with uncontrolled hypertension, currently taking metoprolol (beta-blocker) ER 200 mg daily, lisinopril (angiotensin-converting enzyme inhibitor)-hydrochlorothiazide (diuretic) 20-25 mg orally (PO) daily, and doxazosin (alpha-blocker) 4 mg PO daily, with a known allergy to amlodipine (calcium channel blocker)?

Adjusting Antihypertensive Regimen in an Elderly Patient with Uncontrolled Hypertension

Add a non-dihydropyridine calcium channel blocker such as diltiazem extended-release 120-180 mg daily as your next agent, since the patient has an amlodipine allergy and is already on maximal doses of a beta-blocker, ACE inhibitor/thiazide combination, and alpha-blocker. 1

Current Regimen Assessment

Your patient is on a four-drug regimen that represents near-maximal therapy across multiple drug classes:

• Metoprolol ER 200 mg daily - This is at the maximum recommended dose for hypertension 2
• Lisinopril-HCTZ 20-25 mg daily - Lisinopril can be increased to 40 mg daily, and HCTZ to 50 mg daily in elderly patients using 12.5 mg increments 2, 3
• Doxazosin 4 mg daily - This is a reasonable dose, though it can be increased to 8 mg if needed 4

The patient has blood pressure >140 mmHg systolic, indicating uncontrolled stage 1-2 hypertension requiring immediate treatment intensification. 5

Recommended Treatment Algorithm

Step 1: Optimize Current Medications Before Adding a Fifth Agent

First, increase lisinopril from 20 mg to 40 mg daily, as this represents standard dose optimization within the current ACE inhibitor therapy and is well-tolerated in elderly patients. 2, 6 The FDA label explicitly states that usual dosage range is 20-40 mg per day, and doses up to 80 mg have been used. 2

• Lisinopril 40 mg daily has demonstrated effective blood pressure control in elderly patients (ages 65+) with response rates of 68-89% in clinical trials 6
• Age-related differences in antihypertensive efficacy are not clinically significant, and elderly patients tolerate doses from 2.5-40 mg/day effectively 6

Step 2: If BP Remains Uncontrolled After Lisinopril Optimization

Add a non-dihydropyridine calcium channel blocker (diltiazem ER 120-180 mg daily or verapamil ER 120-180 mg daily) as the fifth agent, since dihydropyridine CCBs like amlodipine are contraindicated due to allergy. 1, 5

• This provides an additional complementary mechanism (calcium channel blockade) that works synergistically with your existing regimen 1
• The combination of ACE inhibitor + thiazide + beta-blocker + alpha-blocker + non-DHP CCB targets five different pathophysiologic mechanisms 1

Alternative option if non-DHP CCB is not tolerated: Consider increasing HCTZ from 25 mg to 50 mg daily using 12.5 mg increments, as recommended for elderly patients. 3 However, monitor closely for hypokalemia, hypomagnesemia, and hyperuricemia, which occur more frequently at higher thiazide doses in the elderly. 5

Step 3: Blood Pressure Targets and Monitoring

• Target BP: <140/90 mmHg minimum for this elderly patient, or <130/80 mmHg if well-tolerated and at high cardiovascular risk 1, 5
• Recheck blood pressure within 2-4 weeks after any medication adjustment 5, 7
• Monitor for orthostatic hypotension by checking BP in both sitting and standing positions at each visit, as elderly patients on multiple antihypertensives (especially with doxazosin) have increased risk 5, 4
• Achieve target BP within 3 months of treatment modification 1, 5

Step 4: Critical Assessments Before Further Escalation

Before adding a fifth medication, verify the following:

• Medication adherence - Non-adherence is the most common cause of apparent treatment resistance 1
• Home BP monitoring - Confirm elevated readings with home BP monitoring (target <135/85 mmHg) or 24-hour ambulatory monitoring (target <130/80 mmHg) to rule out white-coat hypertension 1
• Secondary hypertension screening if BP remains severely elevated (≥160/100 mmHg) despite four-drug therapy:
  • Primary aldosteronism 1
  • Renal artery stenosis 1
  • Obstructive sleep apnea 1
  • Interfering medications (NSAIDs, decongestants, stimulants) 1, 3

Step 5: Resistant Hypertension Management

If BP remains uncontrolled on optimized five-drug therapy, add spironolactone 12.5-25 mg daily as the preferred agent for resistant hypertension, provided eGFR >45 mL/min. 1, 7

• Spironolactone provides additional BP reductions of 20-25/10-12 mmHg when added to triple or quadruple therapy 1
• Monitor potassium closely (check within 1-4 weeks) when adding spironolactone to an ACE inhibitor, as hyperkalemia risk is significant 1, 7
• Consider nephrology or hypertension specialist referral if BP remains uncontrolled (≥160/100 mmHg) despite optimal five-drug therapy 1

Critical Pitfalls to Avoid

• Do not add a second beta-blocker - Metoprolol is already at maximum dose, and adding another beta-blocker provides no additional benefit 1
• Do not combine lisinopril with an ARB - Dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without cardiovascular benefit 1
• Do not increase doxazosin as the primary strategy - While doxazosin can be increased to 8 mg, alpha-blockers are less effective than other classes for stroke prevention and cardiovascular events in elderly patients 5, 4
• Avoid high-dose chlorthalidone (>12.5 mg) in elderly patients if switching from HCTZ, as doses above 12.5 mg significantly increase hypokalemia risk (3-fold) and eliminate cardiovascular protection 5
• Monitor for orthostatic hypotension given the combination of doxazosin with multiple other antihypertensives, especially in elderly patients 5, 4

Lifestyle Modifications (Additive to Pharmacotherapy)

Reinforce the following, which provide additive BP reductions of 10-20 mmHg: 1

• Sodium restriction to <2 g/day (produces 5-10 mmHg systolic reduction) 1
• Weight management if overweight (10 kg loss = 6.0/4.6 mmHg reduction) 1
• Regular aerobic exercise (30 minutes most days = 4/3 mmHg reduction) 1
• DASH diet (11.4/5.5 mmHg reduction) 1
• Alcohol limitation to <100 g/week 1