What are the first-line medications and their dosages for the initial management of hypertension?

First-Line Antihypertensive Medications and Dosages

For most adults with hypertension, initiate treatment with a thiazide-type diuretic, specifically chlorthalidone 12.5-25 mg daily, as it has the strongest evidence for reducing cardiovascular events and mortality. 1, 2

Initial Drug Selection by Stage

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

• Start with a single antihypertensive agent and titrate upward before adding additional medications 1
• The preferred first-line agent is a thiazide-type diuretic 3, 1

Stage 2 Hypertension (≥140/90 mmHg or ≥160/100 mmHg)

• Initiate with two first-line agents of different classes, either as separate prescriptions or as a fixed-dose combination 1, 4
• For blood pressure ≥20/10 mmHg above goal, strongly consider starting dual therapy immediately 3

First-Line Medication Classes and Dosages

Thiazide and Thiazide-Like Diuretics (Preferred)

Chlorthalidone (strongest evidence):

• Initial dose: 12.5-25 mg once daily 2
• Maximum dose: 50-100 mg once daily 2
• Superior to hydrochlorothiazide for blood pressure reduction, particularly at night, with longer half-life 3
• Proven superior to lisinopril for stroke prevention and to amlodipine for heart failure prevention 1, 5

Hydrochlorothiazide:

• Initial dose: 12.5-25 mg once daily 3
• Maximum dose: 50 mg once daily 3
• Less potent than chlorthalidone but acceptable alternative when chlorthalidone unavailable 3, 5

ACE Inhibitors

Lisinopril:

• Initial dose: 10 mg once daily 6
• Usual range: 20-40 mg once daily 6
• Maximum dose: 80 mg once daily 6
• For patients on diuretics, start with 5 mg once daily 6

Angiotensin Receptor Blockers (ARBs)

Losartan:

• Initial dose: 50 mg once daily 7
• Maximum dose: 100 mg once daily 7
• For volume-depleted patients (e.g., on diuretics), start with 25 mg once daily 7

Calcium Channel Blockers

Amlodipine:

• Initial dose: 5 mg once daily 8
• Maximum dose: 10 mg once daily 8

Special Population Considerations

Black Patients Without CKD or Heart Failure

• Initiate with thiazide diuretic or calcium channel blocker as first-line therapy 1
• ACE inhibitors are less effective than thiazides and calcium channel blockers for stroke and heart failure prevention in this population 1

Patients with Diabetes and Albuminuria

• Start with ACE inhibitor or ARB to reduce progressive kidney disease risk 1, 4
• Monitor serum creatinine, eGFR, and potassium within 7-14 days after initiation 1, 4

Patients with Coronary Artery Disease

• ACE inhibitors or ARBs are preferred first-line agents 4

Patients with Chronic Kidney Disease and Albuminuria (UACR ≥30 mg/g)

• ACE inhibitors or ARBs strongly recommended 4

Pediatric Patients (≥6 years)

• Lisinopril: 0.07 mg/kg once daily (up to 5 mg), maximum 0.61 mg/kg (up to 40 mg) once daily 3
• Losartan: 0.7 mg/kg once daily (up to 50 mg), maximum 1.4 mg/kg (up to 100 mg) once daily 7

Critical Pitfalls to Avoid

Medication Selection Errors

• Do not use beta-blockers as first-line therapy for uncomplicated hypertension—they are less effective, particularly for stroke prevention in older adults 1, 4
• Do not use alpha-blockers as first-line therapy—they are inferior to other agents for cardiovascular disease prevention 1
• Never combine ACE inhibitors with ARBs—this increases adverse events without additional benefit 4

Monitoring Failures

• Always monitor potassium and renal function within 7-14 days after starting ACE inhibitors, ARBs, or diuretics 1, 4
• Continue monitoring at least annually thereafter 4
• Thiazide diuretics can cause hypokalemia; maintain potassium >3.5 mmol/L to avoid increased ventricular ectopy 3

Dosing Errors

• Avoid high-dose thiazide diuretics—use low doses (chlorthalidone 12.5-25 mg, hydrochlorothiazide 12.5-25 mg) to minimize metabolic side effects while maintaining efficacy 3, 2
• For patients with hepatic impairment, start losartan at 25 mg once daily 7
• For patients with low systolic blood pressure (100-120 mmHg), start lisinopril at 2.5-5 mg once daily 6

Pregnancy Considerations

• ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists are contraindicated in pregnancy and should be avoided in women of childbearing potential without reliable contraception 4

Practical Treatment Algorithm

1. Assess for compelling indications (diabetes with albuminuria, CKD, CAD, heart failure) 1, 4
2. If compelling indications present: Use indicated agent (ACE inhibitor/ARB for diabetes with albuminuria, CKD with albuminuria, or CAD) 1, 4
3. If no compelling indications and non-Black: Start chlorthalidone 12.5-25 mg daily 1, 2
4. If no compelling indications and Black: Start chlorthalidone 12.5-25 mg daily or calcium channel blocker 1
5. Titrate to maximum tolerated dose before adding second agent 1
6. If blood pressure remains uncontrolled: Add second agent from different class (ACE inhibitor/ARB, calcium channel blocker, or additional thiazide if not already using) 3, 1