What are the first-line treatments for Hypertension (HTN)?

First-Line Treatments for Hypertension

For hypertension treatment, initiate lifestyle modifications for all patients with BP >120/80 mmHg, and start pharmacological therapy with one of four first-line medication classes—ACE inhibitors, ARBs, thiazide/thiazide-like diuretics, or dihydropyridine calcium channel blockers—when BP reaches ≥140/90 mmHg in most patients or ≥130/80 mmHg in high-risk patients (those with diabetes, chronic kidney disease, or established cardiovascular disease). 1, 2, 3

Lifestyle Modifications (Foundation for All Patients)

Lifestyle interventions should be implemented immediately for all patients with BP >120/80 mmHg and continued alongside pharmacological therapy when medications are required. 1, 2, 3

Core lifestyle interventions include:

• Weight management: Achieve and maintain BMI 20-25 kg/m² through caloric restriction if overweight or obese 1, 2
• DASH dietary pattern: Emphasize fruits, vegetables, whole grains, lean proteins, and low-fat dairy 1, 3
• Sodium restriction: Limit intake to <2,300 mg/day (approximately 2g sodium) 1, 2
• Potassium supplementation: Increase dietary potassium intake 1, 3
• Physical activity: Minimum 150 minutes of moderate-intensity aerobic exercise weekly, plus resistance training 2-3 times per week 1, 2
• Alcohol limitation: ≤2 drinks/day for men, ≤1 drink/day for women (or <100g/week total, with complete avoidance preferred) 1, 2
• Smoking cessation: Mandatory for all patients 1, 2

Pharmacological Therapy: The Four First-Line Classes

The American Diabetes Association, American College of Cardiology, American Heart Association, and European Society of Cardiology all designate four medication classes as equally effective first-line options, supported by robust evidence demonstrating reduction in cardiovascular morbidity and mortality. 1, 2, 3, 4, 5, 6

The four first-line classes are:

1. ACE inhibitors (e.g., lisinopril) 1, 2, 3, 4
2. Angiotensin Receptor Blockers (ARBs) (e.g., losartan, candesartan) 1, 2, 3
3. Thiazide or thiazide-like diuretics (preferably long-acting agents like chlorthalidone or indapamide over hydrochlorothiazide) 1, 2, 3, 6
4. Dihydropyridine calcium channel blockers (e.g., amlodipine) 1, 2, 3, 5

A 10 mmHg reduction in systolic BP decreases cardiovascular events by 20-30%, underscoring the critical importance of achieving BP control regardless of which first-line agent is selected. 3, 6

Treatment Algorithm Based on BP Severity

BP 130/80-150/90 mmHg (Stage 1 Hypertension)

• Start with a single agent from one of the four first-line classes 1, 3
• Combine with intensive lifestyle modifications 1, 2
• For patients with low cardiovascular risk, consider lifestyle modifications alone for 3-6 months before initiating medication 3, 7
• For patients with high cardiovascular risk (≥10% 10-year ASCVD risk, diabetes, CKD, or established CVD), initiate pharmacological therapy immediately alongside lifestyle modifications 3

BP ≥150/90 mmHg or ≥160/100 mmHg (Stage 2 Hypertension)

• Start with two antihypertensive medications from different classes immediately 1, 2, 3
• Strongly consider single-pill combination formulations to improve adherence 1, 2
• Recommended combinations: RAS blocker (ACE inhibitor or ARB) + dihydropyridine calcium channel blocker OR RAS blocker + thiazide/thiazide-like diuretic 2

Hypertensive Crisis

• Initiate prompt antihypertensive treatment within 1 week maximum, with rapidity dependent on presence of target organ damage 3

Special Population Considerations for Medication Selection

These patient-specific factors should guide your choice among the four first-line classes:

Patients with Albuminuria (UACR ≥30 mg/g)

• Mandatory first-line choice: ACE inhibitor or ARB at maximum tolerated doses 1, 2, 3
• These agents reduce proteinuria and slow progression of kidney disease beyond their BP-lowering effects 1, 3

Patients with Established Coronary Artery Disease

• Preferred first-line choice: ACE inhibitor or ARB 1, 2, 3

Patients with Chronic Kidney Disease

• Preferred first-line choice: ACE inhibitor or ARB to reduce albuminuria and slow CKD progression 3

Black Patients

• Calcium channel blockers or thiazide diuretics are more effective than ACE inhibitors or ARBs when used as monotherapy 1, 2, 3
• If albuminuria or other compelling indication exists, ACE inhibitor or ARB should still be used, potentially in combination with CCB or diuretic 1, 2

Blood Pressure Targets

• Target BP <130/80 mmHg for most adults <65 years 1, 3
• Target systolic BP 120-129 mmHg (or <130 mmHg) for adults ≥65 years if well tolerated 2, 3
• Individualize targets in elderly patients based on frailty, with <140/80 mmHg acceptable in very frail individuals 1, 3
• Achieve BP target within 3 months of treatment initiation 3

Critical Monitoring Requirements

When initiating or adjusting antihypertensive therapy:

• Monitor serum creatinine and potassium levels 7-14 days after initiation or dose changes when using ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists 1, 2, 3
• Monitor for hypokalemia when using diuretics 1
• Watch for hyperkalemia and worsening renal function, particularly in patients with pre-existing renal dysfunction 3
• Follow-up visits should occur 7-14 days after medication initiation or dose changes 1, 3

Critical Caveats and Contraindications

Never combine ACE inhibitors with ARBs—this increases adverse effects (hyperkalemia, acute kidney injury) without additional cardiovascular or renal benefit. 1, 2, 3

ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, direct renin inhibitors, and neprilysin inhibitors are absolutely contraindicated in pregnancy and should be avoided in sexually active individuals of childbearing potential who are not using reliable contraception. 1

Single-pill combination formulations improve medication adherence and should be strongly considered when initiating two-drug therapy. 1, 2

Lifelong treatment is recommended, even beyond age 85 if well tolerated. 2

Escalation Strategy for Uncontrolled BP

• If BP remains uncontrolled on single-agent therapy, add a second medication from a different first-line class 2, 3
• If BP remains uncontrolled on two-drug combination, progress to three-drug combination: RAS blocker + calcium channel blocker + thiazide/thiazide-like diuretic 2
• For patients requiring beta-blockers (for other indications like heart failure or coronary disease), combine with any of the other major BP-lowering drug classes 2