What is the first line of antihypertension treatment and its dosages?

First-Line Antihypertensive Treatment and Dosages

For most patients with hypertension, initiate treatment with a thiazide-like diuretic (chlorthalidone 12.5-25 mg once daily), which has the strongest evidence for reducing cardiovascular mortality, heart failure, and stroke compared to other drug classes. 1, 2

Treatment Initiation Strategy by Blood Pressure Stage

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

• Start with single-agent therapy and titrate dosage before adding sequential agents to reach BP target <130/80 mmHg 1, 2
• Monotherapy is appropriate for patients with lower cardiovascular risk 3

Stage 2 Hypertension (≥140/90 mmHg or ≥20/10 mmHg above target)

• Initiate with two first-line agents of different classes, either as separate medications or fixed-dose combination 1, 2
• This approach accelerates BP control in patients requiring more aggressive treatment 2

First-Line Medication Classes and Specific Dosing

Thiazide-Like Diuretics (Preferred)

Chlorthalidone is the optimal thiazide diuretic based on superior cardiovascular outcomes data and longer duration of action 1, 2, 4:

• Initial dose: 12.5-25 mg once daily 2, 4
• Maximum dose: 100 mg once daily (though doses >50 mg rarely provide additional benefit) 4
• Superior to hydrochlorothiazide for 24-hour BP control, particularly overnight 1, 5
• Demonstrated superiority over amlodipine for heart failure prevention and over lisinopril for stroke prevention 1

Hydrochlorothiazide (acceptable alternative):

• Initial dose: 12.5-25 mg once daily 2, 6
• Maximum dose: 50 mg once daily 2
• Less potent than chlorthalidone 25 mg at equivalent doses 5

Calcium Channel Blockers (Alternative First-Line)

• Amlodipine is the most studied CCB in cardiovascular outcomes trials 1
• CCBs are as effective as diuretics for all cardiovascular events except heart failure 1
• Preferred alternative when thiazide diuretics are not tolerated 1

ACE Inhibitors (Alternative First-Line)

Lisinopril dosing 6:

• Initial dose: 10 mg once daily (5 mg if on concurrent diuretic) 6
• Usual maintenance: 20-40 mg once daily 6
• Maximum dose: 80 mg once daily 6
• Pediatric patients ≥6 years: 0.07 mg/kg once daily (up to 5 mg), maximum 0.61 mg/kg (up to 40 mg) once daily 2, 6

ARBs (Alternative First-Line)

• Equivalent efficacy to ACE inhibitors but better tolerated (less cough and angioedema) 1
• Particularly useful in Black patients who experience ACE inhibitor side effects 1

Population-Specific Recommendations

Black Patients Without Comorbidities

Initiate with thiazide diuretic (especially chlorthalidone) or calcium channel blocker 1, 2:

• ACE inhibitors are notably less effective than CCBs and thiazides for stroke and heart failure prevention in this population 1, 2
• ARBs may be better tolerated than ACE inhibitors but offer no proven advantage over them 1

Patients with Specific Comorbidities

Chronic kidney disease with albuminuria (UACR ≥30 mg/g):

• Start with ACE inhibitor or ARB to reduce progressive kidney disease 2, 3

Diabetes with established coronary artery disease:

• Initiate with ACE inhibitor or ARB 2, 3

Heart failure with reduced ejection fraction:

• Use ACE inhibitor, ARB, or beta-blocker (not thiazide as monotherapy) 3

Medications to Avoid as First-Line

Beta-Blockers

• Not recommended for uncomplicated hypertension due to inferior efficacy 1, 3
• 36% less effective than CCBs and 30% less effective than thiazides for stroke prevention 1
• Reserve for patients with specific indications (coronary disease, heart failure) 3

Alpha-Blockers

• Not used as first-line therapy due to inferior cardiovascular disease prevention compared to thiazides 1

Critical Monitoring and Safety Considerations

Laboratory Monitoring

• Check serum creatinine, eGFR, and potassium within 7-14 days after initiating ACE inhibitors, ARBs, or diuretics 2
• Monitor at least annually thereafter 2
• Maintain potassium >3.5 mmol/L when using thiazide diuretics to avoid ventricular ectopy 2, 5

Common Pitfalls to Avoid

• Never combine ACE inhibitors with ARBs due to lack of added benefit and increased adverse events 2
• Thiazide-induced hypokalemia is associated with glucose intolerance; treating hypokalemia may reverse this effect 5
• NSAIDs blunt thiazide effectiveness 5
• Use lowest effective diuretic dose in patients at high risk for diabetes, preferably combined with renin-angiotensin system blockers 7

Dosing Principles

• Start with low doses to minimize adverse effects 3
• Use once-daily dosing to improve adherence 3
• Titrate to full dose before adding a second agent 3
• Doses above recommended maximums rarely provide additional benefit and increase side effects 4, 7