Initial Medications for Treating Hypertension
For most adults with hypertension, initial treatment should include a combination of an ACE inhibitor or ARB with either a thiazide/thiazide-like diuretic or a dihydropyridine calcium channel blocker. 1
First-Line Medication Classes
Both the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend the following drug classes as first-line treatments for hypertension:
- ACE inhibitors (e.g., lisinopril)
- ARBs (e.g., losartan)
- Thiazide/thiazide-like diuretics (e.g., chlorthalidone, indapamide, hydrochlorothiazide)
- Dihydropyridine calcium channel blockers (e.g., amlodipine)
These four classes have demonstrated the most effective reduction in blood pressure and cardiovascular disease events 1.
Initial Treatment Algorithm
Step 1: Assess Severity of Hypertension
- For BP 130-139/80-89 mmHg: Start with lifestyle modifications for up to 3 months before considering medication 1
- For BP 140-159/90-99 mmHg: Start with single agent or combination therapy 1
- For BP ≥160/100 mmHg or BP >20/10 mmHg above target: Start with combination therapy 1
Step 2: Select Initial Medication Based on Patient Characteristics
| Patient Characteristic | Recommended Initial Treatment |
|---|---|
| Most patients | ACE inhibitor/ARB + diuretic or CCB [1] |
| Black patients | Thiazide diuretic or CCB [1] |
| Patients with albuminuria/CKD | ACE inhibitor or ARB [1] |
| Patients with diabetes | ACE inhibitor or ARB [1,2] |
| Patients with heart failure | ACE inhibitor or ARB [1] |
Medication Specifics
Thiazide/Thiazide-like Diuretics
- Preferred agent: Chlorthalidone (12.5-25 mg daily) due to longer duration of action and stronger evidence in landmark trials 1, 2
- Alternative: Hydrochlorothiazide (12.5-25 mg daily) 3, 4
- Benefits: Low-dose thiazides effectively reduce BP while minimizing metabolic side effects 4, 5
ACE Inhibitors
- Example: Lisinopril starting at 10 mg daily, usual range 20-40 mg 6
- Benefits: Particularly beneficial in patients with diabetes, albuminuria, heart failure 1
ARBs
- When to use: Alternative to ACE inhibitors when not tolerated (e.g., cough) 1
Calcium Channel Blockers
- When to use: Particularly effective in black patients and elderly patients 1
Combination Therapy Approach
The 2024 ESC guidelines strongly recommend:
- Initial combination therapy for most patients with confirmed hypertension (BP ≥140/90 mmHg)
- Preferred combinations: ACE inhibitor/ARB + dihydropyridine CCB or diuretic 1
- Single-pill combinations to improve adherence 1
Special Considerations
Compelling Contraindications
- Avoid ACE inhibitors/ARBs in pregnancy or women planning pregnancy 2
- Avoid combining ACE inhibitors with ARBs 1
Monitoring
- For patients on ACE inhibitors, ARBs, or diuretics, monitor serum creatinine, eGFR, and potassium at least annually 1, 7
- Monitor for electrolyte disturbances, particularly with diuretics (hypokalemia, hypomagnesemia) 7
Resistant Hypertension
If BP not controlled on three medications including a diuretic, consider adding spironolactone as fourth-line therapy 1.
Treatment Targets
- General target: <130/80 mmHg for most patients 1, 2
- Elderly patients (65-79 years): 130-139/80 mmHg 2
- Very elderly (≥80 years): 140-150/<80 mmHg 2
The choice of initial antihypertensive medication should be guided by efficacy, tolerability, and specific patient characteristics, with the ultimate goal of reducing morbidity, mortality, and improving quality of life.