What is the first-line treatment for Hypertension (High Blood Pressure)?

First-Line Treatment for Hypertension

For most adults with confirmed hypertension (BP ≥140/90 mmHg), first-line pharmacological treatment should be initiated with one of four equally effective medication classes: thiazide or thiazide-like diuretics (chlorthalidone or indapamide preferred), ACE inhibitors, ARBs, or dihydropyridine calcium channel blockers, combined with lifestyle modifications. 1, 2

Treatment Initiation Based on Blood Pressure Level and Risk

Stage 1 Hypertension (130-139/80-89 mmHg)

• Low cardiovascular risk (<10% 10-year ASCVD risk): Start with lifestyle modifications alone for 3-6 months before considering pharmacotherapy 1
• High cardiovascular risk (≥10% 10-year ASCVD risk, diabetes, CKD, or established CVD): Initiate both lifestyle modifications AND pharmacological therapy immediately 1, 2

Stage 2 Hypertension (≥140/90 mmHg)

• Initiate combination therapy with two antihypertensive agents from different classes immediately, preferably as a single-pill combination 1, 3
• The preferred combination is a RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic 1, 2

Hypertensive Urgency (≥180/110 mmHg)

• Prompt antihypertensive drug treatment is required, with evaluation and treatment initiation within 1 week 1

First-Line Medication Classes

The four primary medication classes have equivalent efficacy in reducing cardiovascular events and mortality 1, 2, 4:

1. Thiazide or thiazide-like diuretics: Chlorthalidone (12.5-25 mg daily) or indapamide (1.25-2.5 mg daily) are preferred over hydrochlorothiazide due to longer half-life and superior cardiovascular outcome data 1, 2, 5

2. ACE inhibitors: Such as lisinopril (10-40 mg daily), enalapril, or ramipril 1, 6

3. ARBs: Such as losartan (50-100 mg daily), candesartan, or olmesartan 1

4. Dihydropyridine calcium channel blockers: Such as amlodipine (5-10 mg daily) 1, 4

Special Population Considerations

Black Patients

• Calcium channel blockers or thiazide diuretics are more effective than ACE inhibitors or ARBs as monotherapy and should be selected as first-line agents 2, 3

Patients with Albuminuria (UACR ≥30 mg/g)

• ACE inhibitor or ARB is mandatory as first-line therapy because these agents reduce albuminuria and slow progression of kidney disease beyond their blood pressure-lowering effects 1, 2
• Continue these medications even as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit 1

Patients with Coronary Artery Disease

• ACE inhibitor or ARB should be selected as first-line therapy 1, 2

Patients with Diabetes

• Treatment is similar to non-diabetic patients unless albuminuria is present, in which case an ACE inhibitor or ARB must be included 1, 3
• Target BP <130/80 mmHg 1

Patients with Heart Failure with Reduced Ejection Fraction

• Beta-blocker plus ACE inhibitor or ARB should be initiated first, followed by mineralocorticoid receptor antagonist and diuretic based on volume status 1, 3

Essential Lifestyle Modifications

All patients with BP >120/80 mmHg should implement 1, 2, 7, 4:

• Sodium restriction to approximately 2 g/day (equivalent to 5 g salt/day) 1, 4
• Weight loss if BMI >25 kg/m², targeting BMI 20-25 kg/m² and waist circumference <94 cm (men) or <80 cm (women) 1, 4
• DASH or Mediterranean diet with increased potassium intake 1, 2, 7, 4
• Moderate-intensity aerobic exercise ≥150 minutes/week (30 minutes, 5-7 days/week) plus resistance training 2-3 times/week 1, 4
• Alcohol restriction to <100 g/week (preferably complete avoidance) 1, 4
• Smoking cessation 1, 7

Critical Monitoring and Safety Considerations

Monitoring Requirements

• Monitor serum creatinine and potassium within 7-14 days after initiating ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists 1, 2
• Repeat BP evaluation in 1 month after medication initiation, with goal of achieving target within 3 months 1, 2

Absolute Contraindications

• Never combine ACE inhibitor with ARB or direct renin inhibitor - this increases adverse events (hyperkalemia, syncope, acute kidney injury) without additional cardiovascular benefit 1, 3
• ACE inhibitors and ARBs are contraindicated in pregnancy and should be avoided in individuals of childbearing potential not using reliable contraception 1, 2

Common Pitfalls

• Beta-blockers are NOT first-line agents for hypertension unless there are compelling indications (prior MI, active angina, heart failure with reduced ejection fraction, or rate control) 1
• Bedtime dosing of antihypertensives is not superior to morning dosing and should not be preferentially recommended 1
• Therapeutic inertia is common - medications should be titrated promptly if BP targets are not achieved 1

Blood Pressure Targets

• <130/80 mmHg for most adults <65 years 2, 4
• SBP <130 mmHg for adults ≥65 years (or <140/80 mmHg based on frailty considerations) 1, 2