First-Line Treatment for Hypertension
For most patients with hypertension, first-line treatment should include one of the four major drug classes: thiazide or thiazide-like diuretics, ACE inhibitors, ARBs, or dihydropyridine calcium channel blockers, with initial low-dose combination therapy recommended for most patients with confirmed hypertension. 1
Initial Pharmacological Approach
Blood Pressure Thresholds for Treatment
- For BP 130/80-150/90 mmHg: Consider starting with a single agent
- For BP ≥150/90 mmHg: Start with two-drug combination therapy 1
First-Line Medication Selection
Major drug classes (all equally effective as first-line options):
- Thiazide or thiazide-like diuretics (e.g., chlorthalidone, hydrochlorothiazide)
- ACE inhibitors (e.g., lisinopril, ramipril)
- ARBs (e.g., losartan, valsartan)
- Dihydropyridine calcium channel blockers (e.g., amlodipine) 1
Special populations with specific first-line recommendations:
Combination Therapy Approach
The 2024 European Society of Cardiology guidelines strongly recommend upfront low-dose combination therapy for most patients with confirmed hypertension, preferably as single-pill combinations 1. This approach:
- Targets multiple pathophysiological pathways
- Allows lower doses of individual medications
- May reduce side effects
- Improves adherence
- Achieves faster blood pressure control 1
Evidence Supporting First-Line Choices
The ALLHAT trial, one of the largest hypertension trials, demonstrated that chlorthalidone (a thiazide-like diuretic) was as effective as amlodipine (CCB) and lisinopril (ACE inhibitor) for the primary outcome of fatal CHD or nonfatal MI 2. However, chlorthalidone was superior to:
- Amlodipine in preventing heart failure
- Lisinopril in preventing stroke and combined cardiovascular disease 2
Lifestyle Modifications
Alongside pharmacological therapy, recommend these lifestyle modifications:
- Weight loss if overweight/obese
- DASH-style dietary pattern
- Sodium reduction (<2,300 mg/day)
- Increased potassium intake
- Physical activity (≥150 min/week)
- Limited alcohol consumption
- Smoking cessation 1, 3
Monitoring and Follow-up
- For patients on ACE inhibitors, ARBs, or diuretics: Monitor serum creatinine/eGFR and potassium levels at baseline, 2-4 weeks after initiation or dose changes, and at least annually 1
- Schedule follow-up BP checks within 2-4 weeks of medication adjustment 3
Common Pitfalls to Avoid
- Inappropriate combinations: Never combine two RAS blockers (ACE inhibitor + ARB) 1
- Inadequate monitoring: Failure to check electrolytes and renal function after starting ACE inhibitors, ARBs, or diuretics
- Underdosing: Not titrating medications to effective doses
- Overlooking resistant hypertension: If BP remains uncontrolled on three medications, consider adding spironolactone 1
- Pregnancy concerns: ACE inhibitors, ARBs, direct renin inhibitors, and neprilysin inhibitors are contraindicated in pregnancy 1
Algorithmic Approach to First-Line Treatment
- Confirm hypertension diagnosis (BP ≥130/80 mmHg)
- Assess for specific indications:
- If albuminuria or CAD present → ACE inhibitor or ARB
- If Black patient without these conditions → Thiazide diuretic or CCB
- Determine initial therapy based on BP level:
- BP 130/80-150/90 mmHg → Consider single agent
- BP ≥150/90 mmHg → Two-drug combination (preferably single-pill)
- Select optimal combination if needed:
- Preferred: RAS blocker (ACE inhibitor or ARB) + CCB or thiazide diuretic
- Monitor and titrate within 2-4 weeks
- Add third agent if needed (from remaining major class)
- Consider spironolactone for resistant hypertension
By following this evidence-based approach, you can optimize blood pressure control and reduce cardiovascular risk in patients with hypertension.