What is the recommended treatment for uncontrolled hypertension?

Treatment for Uncontrolled Hypertension

For uncontrolled hypertension, a stepwise approach is recommended, starting with combination therapy of ACE inhibitor/ARB plus a calcium channel blocker or thiazide-like diuretic, with the addition of spironolactone as a fourth-line agent if blood pressure remains uncontrolled. 1, 2

Initial Assessment and Diagnosis

• Confirm hypertension diagnosis with proper measurement:

  • Use validated automated upper arm cuff with appropriate size
  • Measure BP in both arms at first visit (use arm with higher reading)
  • Office BP ≥140/90 mmHg requires confirmation with home or ambulatory monitoring
  • Home BP threshold: ≥135/85 mmHg
  • 24-hour ambulatory BP threshold: ≥130/80 mmHg 1, 2

• Target blood pressure:

  • General population: <130/80 mmHg
  • Elderly patients (≥80 years): <150/90 mmHg
  • Goal: Achieve target within 3 months 2

Stepwise Treatment Algorithm

Step 1: Lifestyle Modifications

• DASH diet (fruits, vegetables, low-fat dairy, reduced sodium)
• Sodium restriction (<2,300 mg/day)
• Regular physical activity (90-150 minutes/week)
• Weight management
• Limited alcohol consumption (≤2 drinks/day for men, ≤1 drink/day for women)
• Smoking cessation 1, 2, 3

Step 2: Initial Pharmacological Therapy

• For non-Black patients:

  1. Start with low-dose ACE inhibitor/ARB (e.g., lisinopril)
  2. Add dihydropyridine calcium channel blocker (e.g., amlodipine)
  3. Increase to full doses 1

• For Black patients:

  1. Start with low-dose ARB + dihydropyridine calcium channel blocker OR
  2. Dihydropyridine calcium channel blocker + thiazide-like diuretic
  3. Increase to full doses 1, 4

Step 3: Add Third Agent

• Add thiazide-like diuretic (e.g., chlorthalidone, indapamide) if not already included
• For Black patients who started with CCB + diuretic, add ACE inhibitor/ARB 1

Step 4: Resistant Hypertension Management

• Add spironolactone (mineralocorticoid receptor antagonist) if BP remains uncontrolled on full doses of three agents
• If spironolactone is contraindicated or not tolerated, consider:
  • Amiloride
  • Doxazosin
  • Eplerenone
  • Clonidine
  • Beta-blocker 1

Special Considerations

• Heart failure with reduced ejection fraction:

  • Start with beta-blocker + ACE inhibitor/ARB
  • Add mineralocorticoid receptor antagonist
  • Add diuretic based on volume status 4

• Chronic kidney disease with proteinuria:

  • Include ACE inhibitor/ARB in regimen
  • Add thiazide diuretic or calcium channel blocker 4

• Diabetes mellitus:

  • Similar approach to general population
  • If proteinuria present, include ACE inhibitor/ARB 4

Monitoring and Follow-up

• Check BP control within 2-4 weeks after medication changes

• Monitor serum creatinine, eGFR, and potassium annually for patients on ACE inhibitors, ARBs, or diuretics

• Monitor more frequently (within 2-4 weeks) after adding a thiazide diuretic 1, 2

• If BP remains uncontrolled despite adherence to the above regimen, refer to a hypertension specialist 1, 2

Common Pitfalls to Avoid

• Do not combine ACE inhibitors with ARBs - increases risk of hyperkalemia without additional benefit 1, 2
• Do not use immediate-release nifedipine in hypertensive crisis - can cause unpredictable drops in BP 5
• Do not delay treatment in patients with BP ≥160/100 mmHg - prompt initiation of combination therapy is recommended 1
• Do not neglect medication adherence assessment - a common cause of uncontrolled hypertension 1, 2
• Do not underestimate the impact of lifestyle modifications - DASH diet alone can have effects equivalent to single drug therapy 3