How to manage severe resistant hypertension in a patient on multiple antihypertensive medications?

Management of Severe Resistant Hypertension in a 77-Year-Old Patient

For this 77-year-old patient with severe resistant hypertension despite 5 antihypertensive medications, with hypokalemia (K 3.05) and preserved renal function, spironolactone should be added as the next agent at a low dose (12.5-25 mg daily). 1, 2, 3

Initial Assessment

Before adding additional medication, confirm true resistant hypertension by:

• Verifying proper BP measurement technique (patient seated quietly for 5 minutes, correct cuff size)
• Considering 24-hour ambulatory BP monitoring to exclude white coat effect
• Assessing medication adherence
• Reviewing for interfering substances (NSAIDs, cold preparations, excessive sodium)
• Evaluating for secondary causes of hypertension

Medication Optimization

1. Review current regimen:

   • Ensure optimal dosing of current medications
   • Verify inclusion of a long-acting thiazide-like diuretic, RAS blocker, and calcium channel blocker
   • Consider switching to single-pill combinations when available to improve adherence

2. Add spironolactone:

   • Start at 12.5-25 mg daily 1, 2
   • Patient's laboratory values make them an ideal candidate:
     • Potassium 3.05 mmol/L (hypokalemia)
     • Creatinine 0.86 mg/dL with eGFR >60 ml/min/1.73m²
   • The International Society of Hypertension specifically recommends spironolactone as the preferred 4th line agent in those with serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 1

3. Monitor:

   • Check potassium and renal function within 1-2 weeks of initiating spironolactone
   • Titrate dose up to 50 mg daily if needed and tolerated 2, 4
   • Studies show spironolactone can provide significant BP reduction (21-25/10-12 mmHg) when added to multidrug regimens 4

Alternative Options if Spironolactone is Contraindicated or Not Tolerated

In order of preference:

1. Eplerenone 25-50 mg daily (alternative MRA with fewer anti-androgenic side effects) 2
2. Amiloride (potassium-sparing diuretic) 1, 5
3. Doxazosin (alpha-1 blocker) 1, 2
4. Clonidine (central alpha-2 agonist) 1, 2
5. Beta-blockers (if heart rate ≥70 bpm) 2
6. Hydralazine (direct vasodilator) 2

Lifestyle Modifications

Emphasize:

• Sodium restriction (<2400 mg/day)
• Weight loss if indicated
• Regular physical activity
• DASH diet
• Limited alcohol intake

Monitoring and Follow-up

• Use ambulatory or home BP monitoring to confirm diagnosis and track treatment response
• Monitor serum creatinine/eGFR and potassium levels closely, especially after adding spironolactone
• Consider referral to a hypertension specialist if BP remains uncontrolled despite these interventions

Common Pitfalls to Avoid

• Failing to confirm true resistant hypertension
• Inadequate diuretic therapy
• Overlooking medication adherence
• Neglecting secondary causes (primary aldosteronism, sleep apnea, renal artery stenosis)
• Inappropriate medication timing
• Overlooking interfering substances

The addition of spironolactone is particularly appropriate for this patient given their hypokalemia (K 3.05), which suggests possible secondary hyperaldosteronism, and preserved renal function (eGFR >60). Multiple guidelines and studies support spironolactone as the most effective fourth-line agent for resistant hypertension 1, 2, 4, 5.