What antihypertensive medication is recommended for the management of hypertension?

Antihypertensive Medication Management

For the management of hypertension, a combination therapy approach using ACE inhibitors or ARBs plus calcium channel blockers (CCBs) is recommended as first-line treatment, with thiazide-like diuretics added as needed for triple therapy. 1, 2

Initial Treatment Approach

Blood Pressure Classification and Initial Therapy

• Normal BP: <120/80 mmHg - No pharmacological intervention needed
• Elevated BP: 120-129/<80 mmHg - Lifestyle modifications
• Stage 1 Hypertension: 130-139/80-89 mmHg - Consider pharmacotherapy, especially with high CV risk
• Stage 2 Hypertension: ≥140/90 mmHg - Initiate combination therapy 1, 2

First-line Medication Selection

1. For most patients with confirmed hypertension:

   • Start with combination of two agents from the four major drug classes:
     • ACE inhibitors (e.g., lisinopril)
     • ARBs
     • Dihydropyridine CCBs
     • Thiazide or thiazide-like diuretics 1, 2
   • Single-pill combinations are preferred to improve adherence

2. For specific populations:

   • Patients with albuminuria or CKD: ACE inhibitor or ARB preferred 1, 2
   • Patients with coronary artery disease: ACE inhibitor or ARB preferred 1, 2
   • Black patients: CCB + thiazide diuretic combination may be more effective 1

Medication Escalation Algorithm

Step 1: Initial Therapy

• For BP 130-150/80-90 mmHg: Consider monotherapy (ACE inhibitor, ARB, CCB, or thiazide diuretic)
• For BP ≥150/90 mmHg: Start with two-drug combination at low doses 1
  • Preferred combinations:
    • ACE inhibitor + CCB
    • ARB + CCB
    • ACE inhibitor + thiazide diuretic
    • ARB + thiazide diuretic 1

Step 2: Inadequate Response

• If BP remains uncontrolled on dual therapy, increase to maximum tolerated doses
• Ensure medication adherence before escalating therapy 2

Step 3: Triple Therapy

• If BP remains uncontrolled on dual therapy, add a third agent:
  • RAS blocker (ACE inhibitor or ARB) + CCB + thiazide diuretic 1
• Use single-pill combinations when possible to improve adherence 1, 2

Step 4: Resistant Hypertension

• If BP remains uncontrolled on triple therapy:
  • Add spironolactone (most effective fourth-line agent)
  • If spironolactone is not tolerated, consider eplerenone, beta-blocker, or alpha-blocker 1

Specific Medication Considerations

ACE Inhibitors (e.g., Lisinopril)

• Benefits: Reduces mortality and CV events, especially beneficial in heart failure and CKD 3
• Dosing: Start at low dose (e.g., lisinopril 5-10 mg daily), titrate as needed
• Monitoring: Check serum creatinine and potassium within 2-4 weeks of initiation
• Cautions: Contraindicated in pregnancy, risk of angioedema, hyperkalemia 2, 3

ARBs

• Benefits: Similar efficacy to ACE inhibitors without cough side effect
• Use: Alternative for patients who develop ACE inhibitor-induced cough
• Cautions: Contraindicated in pregnancy, risk of hyperkalemia in CKD 2

Calcium Channel Blockers

• Benefits: Effective BP reduction, especially in Black patients
• Side effects: Dose-related pedal edema (more common in women)
• Cautions: Avoid in heart failure with reduced ejection fraction 2

Thiazide Diuretics

• Benefits: Proven CV outcome benefits
• Combinations: Effective when combined with ACE inhibitors or ARBs
• Caution: Avoid combining with beta-blockers due to increased risk of new-onset diabetes 1, 2

Monitoring and Follow-up

• Check BP within 2-4 weeks after medication initiation or adjustment
• Monitor serum potassium and renal function within 2-4 weeks after adding ACE inhibitors, ARBs, or diuretics
• Annual monitoring of microalbumin/creatinine ratio to detect early kidney damage 2

Important Considerations and Pitfalls

• Avoid these combinations:

  • Two RAS blockers together (ACE inhibitor + ARB)
  • Beta-blockers + thiazide diuretics (increases diabetes risk) 1

• Pregnancy considerations: ACE inhibitors, ARBs, direct renin inhibitors, and neprilysin inhibitors are contraindicated in pregnancy and in women planning pregnancy 1

• Medication adherence: Single-pill combinations improve adherence and should be preferred when possible 1, 2

• Lifestyle modifications: Always implement alongside pharmacotherapy:

  • Sodium restriction (<2,300 mg/day)
  • DASH or Mediterranean diet
  • Regular physical activity (150 min/week)
  • Weight management
  • Limited alcohol consumption
  • Smoking cessation 2

By following this algorithm-based approach to antihypertensive therapy, clinicians can effectively manage hypertension while minimizing adverse effects and optimizing cardiovascular outcomes.