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

First-Line Treatment for Hypertension

For most patients with hypertension, first-line pharmacological therapy should include one of four medication classes: thiazide or thiazide-like diuretics, ACE inhibitors, ARBs, or dihydropyridine calcium channel blockers, combined with lifestyle modifications. 1, 2, 3

Initial Treatment Algorithm

Step 1: Lifestyle Modifications (All Patients)

• Sodium restriction to <2,300 mg/day (approximately 2g/day) is recommended for all patients with elevated blood pressure 1, 3
• Weight loss targeting BMI 20-25 kg/m² and waist circumference <94 cm (men) or <80 cm (women) if overweight 1
• Moderate-intensity aerobic exercise ≥150 minutes/week plus resistance training 2-3 times/week 1
• Adopt Mediterranean or DASH dietary patterns with increased potassium intake 1, 2
• Alcohol limitation to <100g/week of pure alcohol (complete avoidance preferred) 1
• Smoking cessation 1

Step 2: Determine Need for Pharmacological Therapy

For BP ≥140/90 mmHg: Initiate both lifestyle modifications and pharmacological treatment immediately 1, 2

For BP 130-139/80-89 mmHg with high cardiovascular risk (established CVD, diabetes, CKD, or ≥10% 10-year ASCVD risk): Initiate pharmacological treatment after 3 months of lifestyle intervention 1, 2

For BP ≥150/90 mmHg: Start with two antihypertensive medications from different classes immediately 4

Step 3: Select First-Line Medication Based on Patient Characteristics

General Population (No Comorbidities)

Combination therapy with a RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker or thiazide-like diuretic is recommended as initial therapy for most patients with confirmed hypertension 1

The four equally effective first-line classes are 1, 2, 3:

• Thiazide-like diuretics (chlorthalidone and indapamide preferred over hydrochlorothiazide due to superior cardiovascular event reduction) 4
• ACE inhibitors (e.g., enalapril, lisinopril)
• ARBs (e.g., candesartan, losartan)
• Dihydropyridine calcium channel blockers (e.g., amlodipine)

Special Populations Requiring Specific First-Line Agents

Patients with albuminuria (UACR ≥30 mg/g): ACE inhibitor or ARB is mandatory first-line therapy to reduce proteinuria and slow kidney disease progression 4, 1, 2

Patients with coronary artery disease: ACE inhibitor or ARB is recommended as first-line therapy 4, 1, 2

Patients with diabetes and albuminuria (UACR ≥300 mg/g): ACE inhibitor or ARB is strongly recommended 4

Black patients: Calcium channel blockers or thiazide diuretics are more effective than ACE inhibitors or ARBs when used as monotherapy 1, 2

Patients with prior MI, active angina, or heart failure with reduced ejection fraction: Beta-blockers are indicated in addition to other first-line agents 4

Step 4: Titration and Escalation

If BP not controlled with two-drug combination: Progress to three-drug combination (RAS blocker + calcium channel blocker + thiazide-like diuretic) 1

If BP not controlled with three drugs from different classes: Consider adding a mineralocorticoid receptor antagonist and refer to specialist with expertise in BP management 4

Use fixed-dose single-pill combinations to improve medication adherence 1

Blood Pressure Targets

• Target <130/80 mmHg for most adults <65 years 2
• Target systolic BP 120-129 mmHg in most adults if well tolerated 1
• Target systolic BP <130 mmHg for adults ≥65 years 2, 3

Critical Monitoring Requirements

Monitor serum creatinine and potassium within 7-14 days after initiation of ACE inhibitors, ARBs, or diuretics, then at least annually 4, 2

Follow-up within 7-14 days after medication initiation or dose changes, with goal of achieving BP target within 3 months 2

Essential Caveats and Contraindications

Never combine ACE inhibitors with ARBs due to increased risk of hyperkalemia, syncope, and acute kidney injury without added cardiovascular benefit 4, 1, 2

Never combine ACE inhibitor or ARB with direct renin inhibitor due to lack of benefit and increased adverse events 4

ACE inhibitors and ARBs are contraindicated in pregnancy and should be avoided in sexually active individuals of childbearing potential not using reliable contraception 2

Adding mineralocorticoid receptor antagonists to ACE inhibitor or ARB increases hyperkalemia risk, requiring regular monitoring of serum creatinine and potassium 4

Continue ACE inhibitor or ARB therapy even as kidney function declines to eGFR <30 mL/min/1.73 m² for cardiovascular benefit without significantly increasing end-stage kidney disease risk 4

Bedtime dosing of antihypertensives is not recommended as prior benefits have not been reproduced in subsequent trials 4

Evidence Quality Note

The recommendation for combination therapy as initial treatment represents the most recent guideline consensus from the European Society of Cardiology (2025) 1, which differs slightly from earlier approaches that favored monotherapy initiation in some patients. A 10 mmHg reduction in systolic BP decreases cardiovascular events by 20-30%, emphasizing the importance of achieving target BP promptly 3.