What are the first-line medications for managing hypertension?

First-Line Medications for Hypertension Management

The first-line medications for managing hypertension include thiazide or thiazide-like diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and dihydropyridine calcium channel blockers (CCBs). 1, 2

Initial Treatment Approach

Medication Selection

• For most patients with uncomplicated hypertension: Any of the four major drug classes can be used as first-line therapy:
  • Thiazide or thiazide-like diuretics (e.g., hydrochlorothiazide, chlorthalidone)
  • ACE inhibitors (e.g., lisinopril)
  • ARBs (e.g., losartan)
  • Dihydropyridine CCBs (e.g., amlodipine)

Special Populations

• For patients with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g): ACE inhibitors or ARBs should be the initial treatment to reduce the risk of progressive kidney disease 1
• For patients with established coronary artery disease: ACE inhibitors or ARBs are recommended first-line 1
• For Black patients: Thiazide diuretics or CCBs may be more effective as initial therapy compared to ACE inhibitors 1
• For patients with diabetes and albuminuria: ACE inhibitors or ARBs are preferred first-line agents 2

Combination Therapy Considerations

For many patients, combination therapy will be necessary to achieve blood pressure goals:

• For blood pressure between 130/80 mmHg and 160/100 mmHg: Starting with a single agent may be appropriate 1

• For blood pressure ≥160/100 mmHg: Initial treatment with two antihypertensive medications is recommended 1

• Preferred combinations:

  • ACE inhibitor or ARB + thiazide diuretic
  • ACE inhibitor or ARB + CCB
  • CCB + thiazide diuretic

• Combinations to avoid:

  • ACE inhibitor + ARB (increases risk of adverse effects without additional benefit) 1, 2
  • ACE inhibitor or ARB + direct renin inhibitor 1

Dosing and Monitoring

• Start with lower doses and titrate based on blood pressure response
• Monitor blood pressure within 1-2 weeks of starting or adjusting medication 2
• For patients on ACE inhibitors, ARBs, or diuretics, monitor serum creatinine/estimated glomerular filtration rate and potassium levels at least annually 1

Resistant Hypertension Management

If blood pressure remains uncontrolled on three classes of antihypertensive medications (including a diuretic):

• Consider adding a mineralocorticoid receptor antagonist (e.g., spironolactone) 1
• Evaluate for secondary causes of hypertension
• Assess medication adherence and address barriers to treatment

Clinical Evidence Strength

The recommendations for first-line agents are strongly supported by multiple guidelines. The European Society of Cardiology (2024) 1, American College of Cardiology/American Heart Association (2018) 1, and American Diabetes Association (2019,2023) 1 all consistently recommend the same four major drug classes as first-line therapy.

The most recent evidence from the European Society of Cardiology (2024) supports upfront combination therapy for most patients with confirmed hypertension, preferably as single-pill combinations to improve adherence 1.

Common Pitfalls to Avoid

• Inadequate initial therapy: For patients with significantly elevated blood pressure (≥160/100 mmHg), starting with a single agent is often insufficient
• Inappropriate combinations: Combining ACE inhibitors with ARBs increases adverse effects without additional benefit
• Overlooking comorbidities: Failing to consider conditions like diabetes, chronic kidney disease, or coronary artery disease when selecting initial therapy
• Insufficient monitoring: Not checking electrolytes and renal function in patients on RAS blockers or diuretics
• Neglecting lifestyle modifications: Diet, exercise, sodium restriction, and weight management remain important adjuncts to pharmacological therapy

By following these evidence-based recommendations and considering patient-specific factors, hypertension can be effectively managed to reduce cardiovascular morbidity and mortality.