What is the first-line treatment for Hypertension (HTN)?

First-Line Treatment for Hypertension

The first-line treatment for hypertension should be a thiazide or thiazide-like diuretic, an ACE inhibitor/ARB, or a calcium channel blocker, with specific agent selection based on patient characteristics. 1, 2

Initial Pharmacologic Therapy Selection

General Population

• Thiazide or thiazide-like diuretics (particularly chlorthalidone 12.5-25 mg daily) are preferred first-line agents due to their proven efficacy in reducing cardiovascular events 1, 3
• ACE inhibitors (e.g., lisinopril) or ARBs (e.g., losartan) are equally effective first-line options 1, 2
• Calcium channel blockers (e.g., amlodipine) are also appropriate first-line agents 2, 4

Special Populations

• Black patients: Thiazide diuretics or calcium channel blockers are more effective as initial therapy 1, 5
• Patients with diabetes: ACE inhibitor or ARB is recommended first-line, especially with albuminuria 5
• Patients with coronary artery disease: ACE inhibitor or ARB is recommended first-line 5
• Patients with chronic kidney disease and albuminuria: ACE inhibitor or ARB is strongly recommended 5

Initial Monotherapy vs. Combination Therapy

• For BP 130/80-160/100 mmHg: Start with a single agent 5
• For BP ≥160/100 mmHg: Start with two-drug combination therapy 5
  • Fixed-dose combinations improve adherence 5
  • Common effective combinations: ACE inhibitor/ARB + thiazide diuretic or calcium channel blocker 1

Dosing and Titration

• Begin with standard starting doses and titrate every 2-4 weeks until target BP is achieved 1
• Monitor serum potassium, sodium, and renal function within 1 month of starting therapy, especially with ACE inhibitors, ARBs, or diuretics 1

Target Blood Pressure Goals

• Most adults: <130/80 mmHg 1, 2
• Adults 65-79 years: 130-139/80 mmHg 1
• Adults ≥80 years: 140-150/<80 mmHg 1

Management of Resistant Hypertension

• Resistant hypertension is defined as BP ≥140/90 mmHg despite therapy with three antihypertensive drugs including a diuretic 5
• Consider adding a mineralocorticoid receptor antagonist (spironolactone) as fourth-line therapy 5, 1

Important Considerations and Pitfalls

Common Pitfalls

1. Inadequate initial dosing: Starting with doses that are too low may delay achieving BP control
2. Therapeutic inertia: Failure to titrate or add medications when BP targets are not met
3. Not accounting for patient characteristics: Failing to consider age, race, and comorbidities when selecting therapy
4. Poor adherence monitoring: Not addressing medication adherence issues

Medication Monitoring

• Monitor for electrolyte disturbances with diuretics (hypokalemia, hyponatremia)
• Watch for cough with ACE inhibitors
• Check for edema with calcium channel blockers
• Monitor renal function with ACE inhibitors and ARBs, especially in patients with CKD 1

Lifestyle Modifications

Always recommend concurrent lifestyle modifications:

• Sodium restriction (<2400 mg/day)
• DASH diet (rich in fruits, vegetables, low-fat dairy; low in red meat and fats)
• Regular physical activity
• Weight management
• Alcohol moderation (≤2 drinks/day for men, ≤1 drink/day for women) 1, 2

The evidence strongly supports that proper selection of first-line antihypertensive therapy based on patient characteristics, along with appropriate dosing and monitoring, leads to significant reductions in cardiovascular morbidity and mortality. Thiazide diuretics have particularly strong evidence for reducing all-cause mortality and cardiovascular events 6, 3.