How to manage a patient with resistant hypertension on hydralazine, Losartan, and amlodipine?

Management of Resistant Hypertension

For a patient with resistant hypertension on hydralazine 25 mg TID, losartan 50 mg BID, and amlodipine 10 mg daily, the most effective next step is to add spironolactone 25 mg daily as a fourth agent to the regimen. 1, 2

Confirming True Resistant Hypertension

Before adding additional medications, confirm this is true resistant hypertension:

1. Verify proper BP measurement technique (patient seated quietly for 5 minutes, correct cuff size)
2. Assess medication adherence through direct questioning
3. Consider 24-hour ambulatory BP monitoring to exclude white-coat effect
4. Review for interfering substances (NSAIDs, cold preparations, excessive sodium intake)

Optimization of Current Regimen

The current regimen has several issues that should be addressed:

• Diuretic selection: The patient is on losartan (RAS blocker) and amlodipine (CCB) but using hydralazine as the third agent instead of a diuretic
• Dosing optimization:
  • Hydralazine 25 mg TID is not at maximum dose (can be increased to 50 mg QID) 3
  • Losartan 50 mg BID could be optimized to 100 mg daily (once-daily dosing may improve adherence)

Step-by-Step Management Algorithm

Step 1: Optimize the three-drug regimen

1. Add appropriate diuretic: Replace hydralazine with a thiazide-like diuretic (chlorthalidone 12.5-25 mg daily or indapamide 1.25-2.5 mg daily) 1
2. Maximize lifestyle interventions:
   • Sodium restriction (<2400 mg/day)
   • Weight loss if overweight/obese
   • Regular physical activity
   • DASH diet
   • Limit alcohol intake

Step 2: If BP remains uncontrolled after optimizing the three-drug regimen

Add spironolactone 25 mg daily as the fourth agent 1, 2

• Start at 12.5-25 mg daily
• Monitor potassium and renal function
• Can titrate up to 50 mg daily if needed and tolerated

Step 3: If BP remains uncontrolled or spironolactone is not tolerated

Consider these options in sequence:

1. Eplerenone 25-50 mg daily (alternative MRA) 1, 2
2. Add a beta-blocker (if heart rate ≥70 bpm) 1, 2
   • Preferred options: metoprolol succinate, bisoprolol, or combined α-β-blocker (labetalol, carvedilol)
3. If beta-blocker contraindicated, consider central α-agonist (clonidine patch weekly or guanfacine at bedtime) 1

Step 4: If BP still not controlled

1. Increase hydralazine to maximum dose (50 mg QID) 1, 3
2. Consider minoxidil as a last resort for truly refractory cases 1

Special Considerations

• Medication timing: Consider evening dosing of at least one antihypertensive agent
• Single-pill combinations: Use when available to improve adherence
• Secondary causes: Consider screening for primary aldosteronism, chronic kidney disease, sleep apnea, and renal artery stenosis if BP remains difficult to control 2

Common Pitfalls to Avoid

• Failing to confirm true resistant hypertension before adding medications
• Inadequate diuretic therapy (inappropriate type or dose)
• Not addressing medication adherence issues
• Using suboptimal medication dosing schedules
• Overlooking secondary causes of hypertension

By following this systematic approach, blood pressure control can be achieved in most patients with resistant hypertension, reducing their cardiovascular risk and improving outcomes.