What is the first line treatment for hypertension (HTN)?

First-Line Treatment for Hypertension

The first-line treatment for hypertension should include thiazide diuretics, ACE inhibitors, ARBs, or calcium channel blockers, with thiazide-like diuretics being preferred due to their proven efficacy in reducing cardiovascular events. 1, 2

Initial Medication Selection Algorithm

Step 1: Assess Patient Characteristics

• For patients without comorbidities: Thiazide-like diuretics (chlorthalidone preferred over hydrochlorothiazide) 1, 3
• For patients with albuminuria (UACR ≥30 mg/g): ACE inhibitor or ARB 1
• For patients with diabetes and albuminuria: ACE inhibitor or ARB 1
• For patients with coronary artery disease: ACE inhibitor or ARB 1, 2

Step 2: Consider Severity of Hypertension

• BP 140/90-159/99 mmHg: Start with single agent 1
• BP ≥160/100 mmHg: Start with two-drug combination 1

Medication Options and Evidence

Thiazide Diuretics

• Preferred first-line agent with strongest evidence for reducing cardiovascular events 1, 3
• Chlorthalidone is preferred over hydrochlorothiazide due to superior efficacy and outcomes 4, 3
• Dosing: Chlorthalidone 12.5-25 mg daily 2

ACE Inhibitors

• Effective for reducing cardiovascular events and mortality 1, 5
• Particularly beneficial for patients with albuminuria, diabetes, or heart failure 1
• Example: Lisinopril 10-40 mg daily 5

Angiotensin Receptor Blockers (ARBs)

• Alternative to ACE inhibitors when not tolerated (less cough and angioedema) 1, 2
• Equally effective for patients with albuminuria 1

Calcium Channel Blockers

• Dihydropyridine type (e.g., amlodipine) is preferred 1, 6
• Particularly effective in black patients 1
• Dosing: Amlodipine 2.5-10 mg daily 6

Combination Therapy Considerations

For patients requiring multiple medications:

• Effective combinations 1, 2:

  • Thiazide diuretic + ACE inhibitor or ARB
  • Calcium channel blocker + ACE inhibitor or ARB
  • Calcium channel blocker + thiazide diuretic

• Avoid these combinations 1:

  • ACE inhibitor + ARB (increased adverse effects without additional benefit)
  • ACE inhibitor or ARB + direct renin inhibitor

Special Populations

Black Patients

• Thiazide diuretics or calcium channel blockers are more effective than ACE inhibitors 1

Elderly Patients (≥65 years)

• Start with lower doses and titrate carefully 2
• Target BP <130 mmHg if tolerated 2

Resistant Hypertension

• Add mineralocorticoid receptor antagonist (spironolactone 25-50 mg) when three-drug regimen including a diuretic fails 1, 2

Monitoring

• For patients on ACE inhibitors, ARBs, or diuretics: Monitor serum creatinine/eGFR and potassium at least annually 1
• Monitor for orthostatic hypotension, especially in elderly patients 2

Common Pitfalls to Avoid

1. Using beta-blockers as first-line therapy (less effective than other classes for primary prevention) 1
2. Using hydrochlorothiazide instead of chlorthalidone (chlorthalidone has better evidence) 3
3. Combining ACE inhibitors with ARBs (increases adverse effects without additional benefit) 1
4. Delaying combination therapy in patients with stage 2 hypertension (BP ≥160/100 mmHg) 1
5. Not considering drug interactions (e.g., NSAIDs can reduce effectiveness of ACE inhibitors) 2

By following this evidence-based approach to selecting first-line antihypertensive therapy, clinicians can optimize blood pressure control and reduce cardiovascular morbidity and mortality in patients with hypertension.