What is the next step in managing a patient with uncontrolled hypertension (blood pressure 160/90) on hydrochlorothiazide (HCTZ) 12.5 mg daily and amlodipine 5 mg at night?

Management of Uncontrolled Hypertension on Current Dual Therapy

Immediate Next Step

Increase the dose of amlodipine from 5 mg to 10 mg daily, as this patient has Grade 2 hypertension (160/90 mmHg) requiring immediate intensification of therapy. 1, 2

Rationale for Dose Escalation

• The patient is on suboptimal doses of both medications: hydrochlorothiazide 12.5 mg is the minimum dose, and amlodipine 5 mg is only the initial dose 2, 3
• Amlodipine can be safely titrated to 10 mg once daily, which is the maximum and most effective dose for blood pressure control 2
• The FDA label specifies that most patients with hypertension require 10 mg of amlodipine for adequate effect 2
• Titration should occur after 7-14 days, though more rapid titration is appropriate when clinically warranted with frequent assessment 2

Subsequent Management if Blood Pressure Remains Uncontrolled

Add a Third Agent from a Different Class

If blood pressure remains ≥160/90 mmHg after maximizing amlodipine, add an ACE inhibitor or ARB to create a triple-therapy regimen 4

• A triple regimen of ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic is effective and generally well tolerated 4
• This combination addresses multiple mechanisms: volume control (diuretic), vasodilation (calcium channel blocker), and renin-angiotensin system blockade 4, 5

Consider Switching or Intensifying Diuretic Therapy

Chlorthalidone 25 mg should be considered instead of hydrochlorothiazide 12.5 mg, as it provides superior 24-hour blood pressure reduction 4

• Studies demonstrate chlorthalidone is more effective than hydrochlorothiazide at equivalent doses, with the largest difference occurring overnight 4
• Chlorthalidone has demonstrated outcome benefits in clinical trials 4
• Inadequate diuretic therapy is the most common cause of apparent treatment resistance 4

Add Mineralocorticoid Receptor Antagonist

If blood pressure remains uncontrolled on three medications, add spironolactone 12.5-50 mg daily 4

• Spironolactone added to multidrug regimens (including diuretic + ACE inhibitor/ARB) lowered blood pressure by an additional 25/12 mmHg in resistant hypertension 4
• This benefit occurs regardless of baseline aldosterone levels 4
• Monitor potassium closely, especially in patients with chronic kidney disease, diabetes, or those on ACE inhibitors/ARBs 4

Blood Pressure Goals and Monitoring

• Target blood pressure: <130/80 mmHg 1
• Initial goal: reduce blood pressure by at least 20/10 mmHg 1
• Achieve target within 3 months 1
• Follow-up in 2-4 weeks after any medication adjustment 1
• Consider home blood pressure monitoring to improve adherence and track progress 1

Critical Assessment Before Escalation

Rule Out Pseudoresistance

• Confirm elevated readings with at least two additional measurements using a validated device with appropriate cuff size 1
• Assess medication adherence—this is the most common reason for apparent treatment failure 6
• Consider white-coat hypertension if office readings are consistently elevated but home readings are controlled 6

Identify Contributing Factors

• NSAIDs are a major contributor to resistant hypertension and should be discontinued if possible 4, 6
• High dietary sodium intake (recommend <100 mEq/24 hours) 4
• Heavy alcohol consumption (limit to ≤2 drinks/day for men, ≤1 drink/day for women) 4
• Obesity—10 kg weight loss reduces blood pressure by approximately 6/4.6 mmHg 4

Screen for Secondary Causes

If blood pressure remains uncontrolled on ≥3 medications at optimal doses, evaluate for secondary hypertension 1, 6

• Chronic kidney disease (check creatinine clearance) 4, 6
• Obstructive sleep apnea (especially in obese patients) 6
• Primary aldosteronism (consider in resistant hypertension) 4, 6

Important Caveats

• If creatinine clearance is <30 mL/min, loop diuretics (furosemide or torsemide) are necessary instead of thiazide diuretics 4
• Timing of medications matters: taking at least one antihypertensive at bedtime improves 24-hour control and lowers nighttime blood pressure 4
• Refer to a hypertension specialist if blood pressure remains ≥160/100 mmHg on ≥3 medications or if multiple drug intolerances occur 4, 1