What is the approach to managing resistant hypertension?

Management of Resistant Hypertension

The management of resistant hypertension requires a stepwise approach starting with confirmation of true resistance, optimization of lifestyle factors, evaluation for secondary causes, and sequential medication adjustments following the American Heart Association's algorithm, with spironolactone being the preferred fourth-line agent for most patients. 1, 2

Definition and Confirmation

Resistant hypertension is defined as:

• Blood pressure remaining above goal (>140/90 mmHg) despite concurrent use of 3 antihypertensive agents of different classes at optimal doses, including a diuretic
• OR blood pressure at goal but requiring 4 or more medications

Before proceeding with treatment intensification:

1. Rule out pseudoresistance:

   • Confirm with out-of-office measurements (24-hour ambulatory monitoring)
   • Assess medication adherence (approximately 50% of apparent resistance)
   • Ensure proper BP measurement technique
   • Evaluate for white coat effect

2. Identify contributing factors:

   • Interfering substances (NSAIDs, stimulants, decongestants)
   • Excessive sodium intake
   • Alcohol consumption
   • Obesity
   • Physical inactivity

Evaluation for Secondary Causes

Investigate for secondary causes, particularly:

• Primary aldosteronism
• Obstructive sleep apnea
• Chronic kidney disease
• Renovascular disease
• Pheochromocytoma
• Thyroid disorders
• Hyperparathyroidism

Treatment Algorithm

Step 1: Optimize Lifestyle Interventions

• Sodium restriction (<2400 mg/day)
• DASH diet implementation
• Weight loss if overweight/obese
• Regular physical activity
• Alcohol limitation
• Adequate sleep (≥6 hours uninterrupted)

Step 2: Optimize 3-Drug Regimen

Ensure patient is on optimal doses of:

• RAS blocker (ACE inhibitor or ARB)
• Long-acting calcium channel blocker
• Appropriate diuretic for kidney function

Step 3: Substitute Thiazide-Like Diuretic

• Replace hydrochlorothiazide with chlorthalidone or indapamide
• These maintain efficacy down to eGFR of 30 mL/min/1.73m²

Step 4: Add Mineralocorticoid Receptor Antagonist

• Spironolactone is the preferred 4th agent (12.5-25 mg daily)
• Particularly effective in patients with serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m²
• Eplerenone (50 mg daily) is an alternative with fewer anti-androgenic side effects 3
• Monitor potassium and renal function closely after initiation

Step 5: Add Beta-Blocker or Combined Alpha-Beta Blocker

• If heart rate >70 bpm, add metoprolol succinate, bisoprolol, labetalol, or carvedilol
• If beta-blocker contraindicated, consider central α-agonist (clonidine patch weekly or guanfacine)
• Alternative: once-daily diltiazem

Step 6: Add Vasodilator

• Add hydralazine 25 mg three times daily and titrate upward
• In heart failure with reduced ejection fraction, combine with isosorbide mononitrate

Step 7: Consider Minoxidil

• Substitute minoxidil 2.5 mg two to three times daily for hydralazine and titrate upward
• If BP still not at target, consider referral to hypertension specialist

Monitoring and Follow-up

• Use ambulatory or home BP monitoring to assess treatment response
• Monitor serum creatinine/eGFR and potassium levels after medication changes
• Schedule more frequent clinic visits to enhance adherence
• Consider single-pill combinations to improve compliance

Common Pitfalls to Avoid

1. Inadequate diuretic therapy for volume status
2. Overlooking medication non-adherence
3. Neglecting to screen for secondary causes
4. Inappropriate medication timing
5. Failing to address interfering substances
6. Not maximizing lifestyle modifications
7. Therapeutic inertia (not intensifying treatment despite persistently elevated BP)

By following this structured approach, most patients with resistant hypertension can achieve blood pressure control, reducing their risk of cardiovascular events and mortality 1, 2, 4.