What is the first-line treatment for hypertension?

First-Line Treatment for Hypertension

The first-line treatment for hypertension includes thiazide diuretics, ACE inhibitors, ARBs, or calcium channel blockers, with selection based on patient-specific factors such as comorbidities. 1, 2

Initial Approach to Hypertension Treatment

Lifestyle Modifications

• All patients with blood pressure >120/80 mmHg should begin with lifestyle modifications including weight loss when indicated, DASH diet, sodium restriction (<2,300 mg/day), increased potassium intake, physical activity, smoking cessation, and limited alcohol consumption 1
• These interventions can lower blood pressure and enhance the effectiveness of pharmacological therapy 1

Pharmacological Therapy Initiation

• For patients with blood pressure 130/80-159/99 mmHg, begin with a single antihypertensive agent 1
• For patients with blood pressure ≥160/100 mmHg, initiate treatment with two antihypertensive medications or a single-pill combination 1
• Prompt initiation and timely titration of medications is essential to achieve blood pressure goals 1

First-Line Medication Classes

Recommended First-Line Agents

• Thiazide and thiazide-like diuretics (e.g., chlorthalidone, hydrochlorothiazide) 1, 3
• ACE inhibitors (e.g., lisinopril) 4, 5
• ARBs (e.g., losartan) 6, 5
• Calcium channel blockers (dihydropyridine type, e.g., amlodipine) 1, 2

Medication Selection Based on Comorbidities

• Diabetes with albuminuria: ACE inhibitors or ARBs are recommended as first-line therapy 1
• Coronary artery disease: ACE inhibitors or ARBs are preferred first-line agents 1
• Chronic kidney disease with albuminuria (UACR ≥30 mg/g): ACE inhibitors or ARBs are strongly recommended 1
• Left ventricular hypertrophy: ARBs (such as losartan) have shown benefit in reducing stroke risk 6

Comparative Effectiveness of First-Line Agents

• Thiazide diuretics: Strong evidence for reducing mortality, stroke, coronary heart disease, and cardiovascular events 7, 3
• ACE inhibitors: Effective in reducing mortality, stroke, coronary heart disease, and cardiovascular events 7, 5
• ARBs: Similar effectiveness to ACE inhibitors but with better tolerability and fewer side effects like cough and angioedema 5
• Calcium channel blockers: Effective in reducing stroke and cardiovascular events 7

Special Considerations

Monitoring

• For patients on ACE inhibitors, ARBs, or diuretics: Monitor serum creatinine/eGFR and potassium levels at least annually 1
• More frequent monitoring (7-14 days) is recommended after initiation or dose changes of these medications 1

Combination Therapy

• Multiple-drug therapy is often required to achieve blood pressure targets 1
• Avoid combinations of ACE inhibitors with ARBs due to increased risk of adverse effects without additional benefit 1
• For resistant hypertension (BP ≥140/90 mmHg despite three medications including a diuretic), consider adding a mineralocorticoid receptor antagonist 1

Cautions

• ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, direct renin inhibitors, and neprilysin inhibitors are contraindicated in pregnancy and should be avoided in women of childbearing potential who aren't using reliable contraception 1
• Beta-blockers are not recommended as first-line therapy for uncomplicated hypertension but are indicated for patients with prior MI, active angina, or heart failure 1

Common Pitfalls to Avoid

• Delaying initiation of pharmacological therapy in patients with significantly elevated blood pressure 1
• Using beta-blockers as first-line therapy in uncomplicated hypertension 1
• Combining ACE inhibitors with ARBs 1
• Inadequate monitoring of renal function and electrolytes in patients on ACE inhibitors, ARBs, or diuretics 1
• Failing to recognize and address medication adherence issues in patients with uncontrolled hypertension 1

The most recent evidence supports using any of the four major classes (thiazide diuretics, ACE inhibitors, ARBs, or calcium channel blockers) as first-line therapy, with selection guided by patient-specific factors such as comorbidities, tolerability, and cost considerations 1, 2.