How to manage uncontrolled hypertension in an adult patient?

Managing Uncontrolled Hypertension

Start with two-drug combination therapy as a single-pill combination using a RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker (preferably amlodipine) or a thiazide-like diuretic (preferably chlorthalidone or indapamide), and titrate to achieve a target BP of 120-129/<80 mmHg within 3-6 months. 1, 2

Confirm True Uncontrolled Hypertension

Before intensifying treatment, rule out pseudo-resistance:

• Verify accurate BP measurement technique using proper cuff size, patient positioning (back supported, arm at heart level), and after 3-5 minutes of rest 2, 3
• Obtain home BP monitoring or ambulatory BP monitoring to exclude white coat hypertension, which affects a significant proportion of patients with apparent uncontrolled office readings 1
• Assess medication adherence objectively through pharmacy refill records, as non-adherence accounts for up to 50% of apparent treatment failure and up to 25% of patients never fill their initial prescription 1, 4
• Review interfering substances: NSAIDs, decongestants, stimulants, oral contraceptives, and herbal supplements containing sympathomimetic compounds can elevate BP 1, 3

Pharmacologic Intensification Strategy

First-Line Combination Therapy

• Initiate two-drug combination as single-pill to improve adherence (only 20% of patients maintain adequate adherence with multiple pills) 1, 2, 5
• Preferred combinations: ACE inhibitor (e.g., lisinopril 10-40 mg daily) or ARB plus amlodipine 5-10 mg daily, OR ACE inhibitor/ARB plus chlorthalidone 12.5-25 mg daily 1, 2, 6, 5
• Avoid combining two RAS blockers (ACE inhibitor plus ARB together) 2

Resistant Hypertension Protocol

If BP remains ≥130/80 mmHg on 3 medications at maximum tolerated doses (including a diuretic):

• Switch to chlorthalidone or indapamide if currently using hydrochlorothiazide, as these thiazide-like diuretics are more potent 1
• Add spironolactone 25-50 mg daily as the fourth agent (mineralocorticoid receptor antagonist), which is the most effective add-on therapy 1
• Screen for primary aldosteronism in all patients with resistant hypertension using aldosterone-to-renin ratio; if ratio is low but plasma renin is also low, obtain 24-hour urine aldosterone during high sodium diet 1
• Use loop diuretics instead of thiazides in patients with chronic kidney disease (eGFR <30 mL/min) 1
• Refer to hypertension specialist if BP remains uncontrolled despite 4-drug regimen 1

Lifestyle Modification (Additive to Medications)

These interventions lower BP by 5-6 mmHg each and enhance medication effectiveness:

• Sodium restriction to <2,000 mg/day within 1 month 2, 3, 5
• DASH diet pattern: 4-5 servings fruits, 4-5 servings vegetables, 2-3 servings low-fat dairy daily, limit red meat to <2 servings/week 2, 7, 5
• Weight loss of 5-10% if BMI >25 kg/m² (approximately 1 mmHg reduction per kg lost) 2, 7, 5
• 150 minutes moderate-intensity aerobic exercise weekly (e.g., 30 minutes brisk walking 5 days/week) 2, 7, 5
• Limit alcohol to ≤2 drinks/day for men, ≤1 drink/day for women 2, 7, 5

Home BP Monitoring Protocol

• Measure BP twice daily: morning before medications and evening before supper, taking 2 readings 1 minute apart 2, 4
• Use validated automated monitor with memory storage and appropriate cuff size 1, 2
• Measure daily for 2 weeks after medication changes, then weekly thereafter 4
• Bring stored readings to every appointment for clinical decision-making based on averages from ≥2 occasions 2, 4

Follow-Up Schedule

• Every 2-4 weeks until BP target achieved 4
• Every 3-6 months once controlled 1, 4
• Check electrolytes, creatinine, eGFR 2-4 weeks after medication initiation or dose changes (especially with ACE inhibitors, ARBs, or diuretics) 4, 6
• Contact healthcare team within 48 hours if readings consistently >180/120 mmHg 4

Team-Based Care Implementation

• Engage pharmacists, nurses, or community health workers for medication titration, which can improve BP control rates from 44% to 80% 1, 4
• Use telehealth and secure messaging for between-visit monitoring and medication adjustments 1, 4
• Enable remote monitoring through Wi-Fi-connected BP devices that transmit data directly to the care team 1, 4

Critical Pitfalls to Avoid

• Therapeutic inertia (failing to intensify medications at consecutive visits with uncontrolled BP) is the most common management error—ensure medication adjustment occurs at every visit until goal is reached 1, 4
• Asymptomatic orthostatic hypotension should not be a reason to withhold or down-titrate treatment, as it is not associated with higher rates of CVD events, syncope, or falls 1
• Missing secondary causes in young adults (<40 years) with hypertension—comprehensive screening is mandatory except in obese young adults where sleep apnea evaluation should be performed first 2
• Relying solely on office BP without home or ambulatory monitoring leads to misclassification of white coat or masked hypertension 1, 2