What is the recommended first-line monotherapy antihypertensive treatment for a patient with hypertension?

First-Line Monotherapy for Hypertension

For most patients with hypertension requiring monotherapy, a thiazide or thiazide-like diuretic (preferably chlorthalidone or hydrochlorothiazide) is the recommended first-line agent, as it has the strongest evidence for reducing mortality, cardiovascular events, and stroke compared to other drug classes. 1, 2

When to Use Monotherapy vs. Combination Therapy

Monotherapy is appropriate for:

• Stage 1 hypertension (140-159/90-99 mmHg) in low-to-moderate risk patients 1
• Patients aged >80 years or frail patients 1
• Elevated BP with specific indications for treatment 1

Combination therapy is preferred for:

• Stage 2 hypertension (≥160/100 mmHg) - start two drugs immediately 1
• BP >20/10 mmHg above target - initiate with two first-line agents 1
• Most confirmed hypertension cases - the 2024 ESC guidelines now recommend upfront low-dose combination therapy as Class I for swifter BP control and better adherence 1

First-Line Drug Class Selection Algorithm

For Non-Black Patients:

Start with low-dose ACE inhibitor or ARB 1

• These are the preferred initial agents for non-Black patients
• If monotherapy insufficient, add a dihydropyridine calcium channel blocker (CCB) 1
• Third step: add thiazide/thiazide-like diuretic 1

For Black Patients:

Start with either:

• Low-dose ARB plus dihydropyridine CCB, OR 1
• Dihydropyridine CCB plus thiazide/thiazide-like diuretic 1
• ACE inhibitors are notably less effective in Black patients for stroke and heart failure prevention 1

Special Populations Requiring Specific First-Line Agents:

Coronary artery disease: RAS blockers (ACE inhibitor/ARB) or beta-blockers 1

Heart failure with reduced ejection fraction: RAS blockers, beta-blockers, or mineralocorticoid receptor antagonists 1

Chronic kidney disease with albuminuria (UACR ≥30 mg/g): ACE inhibitor or ARB 1

Diabetes with hypertension: ACE inhibitor, ARB, thiazide-like diuretic, or dihydropyridine CCB 1

Previous stroke: RAS blockers, CCBs, or diuretics 1

Evidence Supporting Thiazide Diuretics as Optimal First Choice

The evidence hierarchy strongly favors thiazide diuretics when no compelling indications exist:

• Chlorthalidone has the highest-level evidence from three major trials involving >50,000 patients, showing superiority to ACE inhibitors for stroke prevention and to CCBs for heart failure prevention 3, 2

• Only thiazide diuretics and ACE inhibitors have demonstrated all-cause mortality reduction compared to placebo 3, 2

• Thiazides reduce cardiovascular events by 0.6-3.1% absolute risk reduction compared to beta-blockers, CCBs, ACE inhibitors, and alpha-blockers 2

• Thiazides reduce heart failure risk by 26-49% compared to CCBs and alpha-blockers 2

The Four Major First-Line Drug Classes

The 2024 ESC guidelines identify four major classes as first-line options 1:

1. ACE inhibitors
2. Angiotensin receptor blockers (ARBs)
3. Dihydropyridine calcium channel blockers
4. Thiazide or thiazide-like diuretics

Never combine two RAS blockers (ACE inhibitor + ARB) - this combination is not recommended 1

Practical Prescribing Considerations

Dosing Strategy:

• Start with low doses to minimize adverse effects 1
• Use once-daily dosing to improve adherence 1
• Titrate to full dose before adding second agent (in monotherapy approach) 1

Common Pitfalls to Avoid:

Beta-blockers are NOT first-line unless compelling indication exists (prior MI, active angina, heart failure) - they are significantly less effective than diuretics for stroke prevention 1, 2

Alpha-blockers are NOT first-line - they are less effective for CVD prevention than thiazide diuretics 1

Avoid rapid BP reduction in hypertensive urgencies - use oral agents and gradual reduction 1

Target Blood Pressure:

• <130/80 mmHg for most adults <65 years 1, 4
• SBP <130 mmHg for adults ≥65 years 4
• Individualize for elderly based on frailty (may accept <140/90 mmHg) 1

Sample Prescription for Standard Patient Without Compelling Indications

Chlorthalidone 12.5 mg once daily (if available) 3, 2

OR

Hydrochlorothiazide 12.5-25 mg once daily (if chlorthalidone unavailable) 3, 2, 4

Reassess BP in 2-4 weeks, titrate to chlorthalidone 25 mg or hydrochlorothiazide 50 mg if needed 1