What are the first-line treatments for hypertension?

First-Line Treatments for Hypertension

For most patients with hypertension, first-line pharmacologic therapy should include ACE inhibitors, ARBs, thiazide or thiazide-like diuretics (preferably chlorthalidone or indapamide), or dihydropyridine calcium channel blockers, initiated as combination therapy for blood pressure ≥140/90 mmHg. 1, 2

Initial Treatment Strategy

Lifestyle Modifications (All Patients)

Before or alongside pharmacologic therapy, implement:

• Sodium restriction to approximately 2g per day 2
• Regular physical activity: ≥150 minutes/week of moderate-intensity aerobic exercise plus resistance training 2-3 times/week 2
• Weight management targeting BMI 20-25 kg/m² and waist circumference <94 cm (men) or <80 cm (women) 2
• Adoption of Mediterranean or DASH dietary patterns 2
• Alcohol limitation to <100g/week of pure alcohol, with complete avoidance preferred 2
• Smoking cessation 2
• Restriction of sugar-sweetened beverages 2

Pharmacologic Therapy Algorithm

Blood Pressure 130-139/80-89 mmHg

• High cardiovascular risk patients: Initiate pharmacologic therapy after 3 months of lifestyle intervention 2
• Lower risk patients: Continue lifestyle modifications and reassess 2

Blood Pressure ≥140/90 mmHg

• Initiate both lifestyle measures and pharmacologic treatment promptly 1, 2
• For BP ≥150/90 mmHg: Start with two antihypertensive medications or single-pill combination immediately 1

First-Line Drug Classes (Equal Efficacy)

The following four classes are proven to reduce cardiovascular events in hypertensive patients:

• ACE inhibitors 1, 2
• Angiotensin receptor blockers (ARBs) 1, 2
• Thiazide-like diuretics (chlorthalidone and indapamide preferred over hydrochlorothiazide) 1, 2
• Dihydropyridine calcium channel blockers 1, 2

Recommended Initial Combination Therapy

For most patients, start with a RAS blocker (ACE inhibitor or ARB) combined with either a dihydropyridine calcium channel blocker OR a thiazide-like diuretic 2

Single-pill fixed-dose combinations are strongly recommended to improve adherence 2

Special Populations Requiring Specific First-Line Agents

Diabetes with Albuminuria (UACR ≥300 mg/g)

ACE inhibitor or ARB at maximum tolerated dose is mandatory as first-line therapy to reduce progressive kidney disease 1

Diabetes with Moderate Albuminuria (UACR 30-299 mg/g)

ACE inhibitor or ARB is suggested as first-line therapy 1

Coronary Artery Disease

ACE inhibitor or ARB is recommended as first-line therapy 1

Heart Failure with Reduced Ejection Fraction

RAS blockers, beta-blockers, and mineralocorticoid receptor antagonists are all first-line agents 1

• Calcium channel blockers should only be added if BP remains uncontrolled 1

Black Patients

Calcium channel blockers or thiazide diuretics may be more effective than ACE inhibitors or ARBs when used as monotherapy 1, 2, 3

• However, combination therapy with a RAS blocker can still be used 1
• Black patients have higher rates of angioedema with ACE inhibitors 3

Prior Myocardial Infarction

Beta-blockers are indicated in addition to standard antihypertensive therapy 1

Treatment Titration

If BP Not Controlled on Two-Drug Combination

Progress to three-drug combination: RAS blocker + calcium channel blocker + thiazide-like diuretic 1, 2

If BP Not Controlled on Three-Drug Combination (Resistant Hypertension)

Add mineralocorticoid receptor antagonist (spironolactone) as fourth-line agent 1

• Monitor serum creatinine and potassium closely due to hyperkalemia risk 1
• Consider referral to hypertension specialist 1

Critical Contraindications and Caveats

Never Combine Two RAS Blockers

Do not use ACE inhibitor + ARB combination, or ACE inhibitor/ARB + direct renin inhibitor combination 1, 2

• This increases adverse events (hyperkalemia, syncope, acute kidney injury) without added cardiovascular benefit 1

ACE Inhibitors/ARBs in Pregnancy

ACE inhibitors, ARBs, direct renin inhibitors, and spironolactone are absolutely contraindicated in pregnancy due to fetal harm 1, 3

• Switch to pregnancy-safe alternatives (methyldopa, labetalol, nifedipine) before conception in women of childbearing potential 1

Monitoring Requirements

Monitor serum creatinine and potassium within 7-14 days after initiating ACE inhibitor/ARB therapy and at least annually 1

• Continue ACE inhibitor/ARB even as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit, unless contraindicated 1

Beta-Blockers Are NOT First-Line

Beta-blockers have not been shown to reduce mortality as blood pressure-lowering agents in the absence of MI, angina, or heart failure with reduced ejection fraction 1

Medication Timing

Take antihypertensive medications at the most convenient time of day to establish a habitual pattern 2

• Bedtime dosing is NOT preferentially recommended 1

Blood Pressure Targets

Target treated systolic BP of 120-129 mmHg in most adults if well tolerated, with general target <130/80 mmHg 2

• For adults ≥65 years: Target SBP <130 mmHg if tolerated 4
• Achieve target within 3 months of treatment initiation 1