What are the first‑line medications used in the United States to treat essential hypertension?

First-Line Medications for Essential Hypertension in the United States

Thiazide diuretics (especially chlorthalidone) and calcium channel blockers are the preferred first-line medications for treating essential hypertension in most U.S. adults, with ACE inhibitors and ARBs serving as equally acceptable alternatives. 1

Primary First-Line Options

The 2017 ACC/AHA guidelines establish four drug classes as appropriate first-line agents for essential hypertension 1:

• Thiazide-type diuretics (particularly chlorthalidone 12.5-25 mg daily) are preferred due to superior efficacy in preventing heart failure and stroke compared to other agents 1, 2
• Calcium channel blockers (dihydropyridine type like amlodipine 5-10 mg daily) are equally effective as thiazides for all cardiovascular events except heart failure 1, 2
• ACE inhibitors (such as lisinopril 10-40 mg daily) are appropriate first-line options, particularly effective in preventing cardiovascular disease 1
• Angiotensin receptor blockers (ARBs) (such as losartan 50-100 mg daily) are equivalent alternatives to ACE inhibitors with better tolerability 1

Why Thiazides and Calcium Channel Blockers Are Preferred

The evidence strongly favors thiazide diuretics and calcium channel blockers over other first-line agents 1:

• Chlorthalidone demonstrated superiority in the ALLHAT trial with 38% lower heart failure rates versus amlodipine and 19% lower heart failure rates versus lisinopril 2, 3
• Stroke prevention favors thiazides and CCBs: ACE inhibitors showed 15% higher stroke rates compared to chlorthalidone 1, 3
• Chlorthalidone is more potent than hydrochlorothiazide at equivalent doses, with better overnight blood pressure control 3

Treatment Initiation Strategy Based on Hypertension Stage

Stage 1 Hypertension (130-139/80-89 mm Hg)

• Start with single-agent therapy using one of the four first-line drug classes 1
• Titrate dosage monthly until blood pressure target <130/80 mm Hg is achieved 1

Stage 2 Hypertension (≥140/90 mm Hg)

• Initiate with two first-line agents from different classes when blood pressure is >20/10 mm Hg above target 1, 2
• Fixed-dose combinations may improve medication adherence 1
• Patients with BP ≥160/100 mm Hg require prompt treatment and careful monitoring 1

Population-Specific Considerations

Black Patients

• Thiazide diuretics and calcium channel blockers are specifically recommended as first-line agents 1
• Beta-blockers and renin-angiotensin system inhibitors (ACE inhibitors/ARBs) are less effective at lowering blood pressure in this population 1
• ACE inhibitors showed 15% higher stroke rates in black patients compared to chlorthalidone 1

Patients with Diabetes

• Any of the four first-line drug classes are appropriate initial therapy 1
• ACE inhibitors or ARBs become preferred if albuminuria (UACR ≥30 mg/g) is present to reduce progressive kidney disease 1
• Treatment threshold is BP ≥130/80 mm Hg with target <130/80 mm Hg 1

Patients with Chronic Kidney Disease

• ACE inhibitors or ARBs are first-line for those with albuminuria to prevent kidney disease progression 1
• Without albuminuria, standard first-line agents (thiazides, CCBs, ACE inhibitors, ARBs) are appropriate 1

Patients with Coronary Artery Disease

• ACE inhibitors or ARBs are recommended as first-line therapy 1
• Beta-blockers are indicated post-myocardial infarction as part of guideline-directed medical therapy 1

Agents to Avoid as First-Line Therapy

Beta-Blockers

• Not recommended as first-line therapy for uncomplicated hypertension 1, 2
• Significantly less effective than diuretics for stroke prevention (30-36% higher stroke risk) 1
• Less effective than CCBs and thiazides for preventing cardiovascular events 1

Alpha-Blockers

• Should not be used as first-line therapy due to inferior cardiovascular disease prevention compared to thiazides 1, 2
• The ALLHAT trial showed 80% higher heart failure rates and 20% higher stroke rates with doxazosin versus chlorthalidone 3

Critical Monitoring Requirements

Initial Monitoring (7-14 days after initiation or dose change)

• Monitor serum creatinine and potassium when using ACE inhibitors, ARBs, or thiazide diuretics 1
• Watch for hypokalemia with diuretics (maintain potassium >3.5 mmol/L to avoid ventricular ectopy) 2
• Monitor for hyperkalemia with ACE inhibitors and ARBs 1

Ongoing Monitoring

• Monthly evaluation of adherence and therapeutic response until blood pressure control is achieved 1
• Annual monitoring of electrolytes and renal function once stable 1

Common Pitfalls to Avoid

Drug Combination Errors

• Never combine ACE inhibitors with ARBs - this increases adverse events including hyperkalemia and acute kidney injury without added benefit 2
• Avoid combining beta-blockers with thiazides when possible, as this may increase fatigue and glucose intolerance 3

Medication Selection Errors

• Use chlorthalidone instead of hydrochlorothiazide when possible - chlorthalidone has superior outcomes data and longer duration of action 2, 3
• Do not use loop diuretics (furosemide) as first-line therapy - they lack outcome data and should be reserved for heart failure or advanced renal failure 3

Dosing Errors

• Avoid using hydrochlorothiazide doses <25 mg daily as monotherapy - the ACCOMPLISH trial used only 12.5-25 mg, which is lower than doses proven effective in placebo-controlled trials 3
• NSAIDs can blunt thiazide effectiveness - consider alternative pain management strategies 3

Contraindications to Remember

• ACE inhibitors, ARBs, and direct renin inhibitors are contraindicated in pregnancy and should be avoided in sexually active individuals of childbearing potential not using reliable contraception 1

Blood Pressure Target

The recommended blood pressure target is <130/80 mm Hg for all patients regardless of ASCVD risk after initiating antihypertensive therapy 1. The evidence supporting this target is strongest for patients with known cardiovascular disease or 10-year ASCVD risk ≥10%, but the same target applies to lower-risk patients 1.