How should uncontrolled hypertension be managed in an adult patient?

Management of Uncontrolled Hypertension in Adults

For adults with uncontrolled hypertension already on treatment, confirm true uncontrolled hypertension using home blood pressure monitoring (HBPM) or ambulatory blood pressure monitoring (ABPM) to exclude white coat effect, then optimize the medication regimen by maximizing diuretic therapy (switching to chlorthalidone or indapamide), adding a mineralocorticoid receptor antagonist as the fourth agent, and screening for secondary causes if resistant hypertension is present. 1

Step 1: Confirm True Uncontrolled Hypertension

Rule out white coat effect first – this is critical because it affects 20-30% of apparent uncontrolled cases and leads to unnecessary treatment intensification. 2

• If office BP is >5-10 mm Hg above goal on 3+ medications, use HBPM to detect white coat effect before escalating therapy. 1
• HBPM targets: <135/85 mm Hg (compared to office target <130/80 mm Hg). 1
• If office BP is at goal but target organ damage or increased CVD risk is present, screen for masked uncontrolled hypertension with HBPM. 1
• White coat effect carries similar CVD risk to controlled hypertension, whereas masked uncontrolled hypertension carries 2-fold higher mortality risk. 1

Step 2: Assess Medication Adherence and Interfering Substances

Non-adherence is the most common cause of apparent resistant hypertension – 25% of patients never fill their initial prescription, and only 20% achieve high adherence. 1, 2

• Objectively assess adherence through pharmacy refill records. 3
• Identify and discontinue or minimize interfering substances:
  • NSAIDs, decongestants, stimulants 1, 3
  • Oral contraceptives 1, 3
  • Herbal supplements containing sympathomimetic compounds 3

Step 3: Optimize Current Medication Regimen

Maximize diuretic therapy first – this is the foundation of resistant hypertension management. 1

• Switch from hydrochlorothiazide to chlorthalidone or indapamide, which provide superior 24-hour BP control. 2, 4
• Use loop diuretics in patients with chronic kidney disease (eGFR <30 mL/min). 1
• Ensure all medications are at optimal doses using drugs with complementary mechanisms of action. 5

Preferred medication combinations:

• RAS blocker (ACE inhibitor or ARB) + dihydropyridine calcium channel blocker + thiazide-like diuretic. 2
• Never combine two RAS blockers (ACE inhibitor + ARB). 2

Step 4: Add Mineralocorticoid Receptor Antagonist

If BP remains uncontrolled on 3 optimized medications (including a diuretic), add spironolactone 25-50 mg/day as the fourth agent – this provides superior BP reduction (average 8-10 mm Hg systolic) compared to other options, even without biochemical evidence of aldosterone excess. 4, 5

• Alternative: eplerenone if spironolactone is not tolerated. 1
• Monitor serum potassium and creatinine when adding these agents. 2

Step 5: Screen for Secondary Causes

Screen for secondary hypertension when resistant hypertension is confirmed (BP ≥130/80 mm Hg on 3+ medications at optimal doses including a diuretic, or requiring 4+ medications). 1

Clinical indications requiring screening: 1

• Abrupt onset or worsening of previously controlled hypertension
• Onset at age <30 years
• Accelerated/malignant hypertension
• Disproportionate target organ damage
• Unprovoked or excessive hypokalemia

Common secondary causes to evaluate:

• Renal parenchymal disease (1-2% prevalence): Check urinalysis, serum creatinine, renal ultrasound. 1
• Renovascular disease (5-34% in resistant hypertension): Listen for abdominal bruit, consider renal Duplex Doppler. 1
• Primary aldosteronism (8-20% in resistant hypertension): Check aldosterone-to-renin ratio. 1
• Obstructive sleep apnea: Assess for snoring, daytime somnolence. 5

If screening is positive, refer to a specialist with expertise in that form of secondary hypertension. 1

Step 6: Reinforce Lifestyle Modifications

Lifestyle changes are additive to pharmacologic therapy and must be maintained:

• Sodium restriction to <2,000 mg/day (ideally <1,500 mg/day) reduces BP by 5-6 mm Hg. 2, 4
• Weight loss of 1 kg reduces BP by approximately 1 mm Hg in overweight patients (BMI ≥25 kg/m²). 4
• Regular aerobic exercise. 2
• Limit alcohol to ≤2 drinks/day for men, ≤1 drink/day for women; reducing intake by 50% in heavy drinkers lowers SBP/DBP by ~5.5/4.0 mm Hg. 2

Step 7: Implement Team-Based Care and Close Monitoring

Use a team-based approach involving physicians, pharmacists, nurses, and health coaches – this improves BP control rates from 44% to 80%. 4

• Schedule follow-up within 1 month after medication changes to assess response and tolerability. 2
• Once stable control is achieved, schedule annual visits for BP reassessment. 2
• Use once-daily dosing and fixed-dose combination pills to improve adherence. 2
• Implement telehealth strategies and electronic health records to guide quality improvement. 1

Step 8: Consider Specialist Referral

Refer to a hypertension specialist if BP remains uncontrolled despite:

• Confirmed adherence to 4+ medications at optimal doses
• Exclusion of white coat effect
• Addressing interfering substances
• Appropriate screening for secondary causes 1

Common Pitfalls to Avoid

• Failing to confirm diagnosis with out-of-office monitoring leads to overtreatment of white coat effect and undertreatment of masked uncontrolled hypertension. 1
• Using hydrochlorothiazide instead of chlorthalidone or indapamide yields inferior BP control. 2
• Underestimating medication non-adherence – routinely assess missed doses, side effects, and cost barriers. 2
• Ignoring interfering substances (NSAIDs, decongestants, stimulants, oral contraceptives) that raise BP. 2
• Not screening for secondary causes in young patients (<30 years) or those with resistant hypertension. 3
• Rapid BP reduction in hypertensive urgency – BP should be reduced gradually over days with oral agents, not hours. 6, 5