What is the protocol for managing resistant hypertension?

Management Protocol for Resistant Hypertension

For resistant hypertension, implement a stepwise approach starting with confirmation of true resistance, followed by optimization of a multi-drug regimen including an ACE inhibitor/ARB, calcium channel blocker, and thiazide-like diuretic, then adding spironolactone as a fourth agent if blood pressure remains uncontrolled. 1

Definition and Confirmation of True Resistant Hypertension

Resistant hypertension is defined as blood pressure ≥140/90 mmHg despite:

• Appropriate lifestyle management
• Concurrent use of 3 antihypertensive medications from different classes at optimal doses
• Including a diuretic in the regimen 1

Before proceeding with treatment intensification, exclude pseudoresistance:

• Medication nonadherence
• White coat hypertension (confirm with out-of-office BP measurements)
• Improper BP measurement technique
• Interfering substances (especially NSAIDs)
• Secondary causes of hypertension 1, 2

Screening for Secondary Causes

Common secondary causes to screen for include:

• Obstructive sleep apnea
• Primary aldosteronism
• Chronic kidney disease
• Renal artery stenosis
• Pheochromocytoma
• Cushing's syndrome
• Thyroid disorders 1

Treatment Algorithm

Step 1: Optimize Lifestyle Modifications

• Dietary sodium restriction (<2,300 mg/day)
• Implement DASH diet
• Weight loss if overweight/obese
• Regular physical activity
• Alcohol limitation
• Adequate sleep (≥6 hours uninterrupted)
• Discontinuation of interfering substances 1

Step 2: Optimize Initial Triple Therapy

Ensure optimal dosing of the three-drug regimen:

• ACE inhibitor or ARB
• Long-acting calcium channel blocker (e.g., amlodipine)
• Thiazide-like diuretic 1, 2

Step 3: Add Fourth Agent

If BP remains uncontrolled after optimizing triple therapy:

• Add spironolactone as the preferred fourth agent (most effective option based on evidence) 1, 2, 3
• Start at 25 mg daily and titrate as needed
• Monitor serum potassium and renal function within 1-2 weeks of initiation 1

Step 4: Alternative Fourth Agents

If spironolactone is not tolerated or contraindicated:

• Amiloride
• Beta-blocker (not metoprolol if already used)
• Alpha-blocker (e.g., doxazosin)
• Eplerenone
• Clonidine 1, 2

Step 5: Consider Referral

• If BP remains uncontrolled after adding spironolactone or alternative fourth agent, consider referral to a hypertension specialist 1

Monitoring and Follow-up

• Check BP within 1 month of medication changes
• Monitor electrolytes and renal function 1-2 weeks after initiation of RAS blockers, diuretics, or spironolactone
• Schedule follow-up at least every 3-6 months once BP is controlled
• Pay special attention to potassium levels when adding spironolactone to ARB therapy due to increased risk of hyperkalemia 1

Special Considerations

• In patients with heart failure and hypertension, consider hydralazine combined with isosorbide dinitrate, particularly in African American patients 1
• For patients requiring additional agents, hydralazine can be considered as a third-line agent at 100-200 mg/day divided into 2-3 doses, always in combination with a beta-blocker to prevent reflex tachycardia 1
• For hypertensive emergencies with end-organ damage, parenteral agents are required with BP reduction within hours; for hypertensive urgency, oral agents with BP reduction over days is appropriate 4

Common Pitfalls to Avoid

1. Failing to confirm true resistance by excluding pseudoresistance
2. Not screening for secondary causes before intensifying therapy
3. Inadequate dosing of the initial three-drug regimen
4. Adding a fourth agent before optimizing the initial three-drug regimen
5. Not monitoring electrolytes and renal function after adding spironolactone
6. Overlooking medication adherence issues or the need for single-pill combinations to improve compliance 1, 2