What are the initial treatment recommendations for hypertension?

Initial Treatment Recommendations for Hypertension

For patients with blood pressure 140-159/90-99 mmHg, start with lifestyle modifications plus a single first-line antihypertensive agent (ACE inhibitor, ARB, thiazide-like diuretic, or calcium channel blocker); for blood pressure ≥160/100 mmHg, initiate two-drug combination therapy immediately, preferably as a single-pill combination. 1, 2, 3

Confirming the Diagnosis

Before initiating pharmacotherapy, confirm hypertension using out-of-office measurements rather than relying solely on office readings 2, 3:

• Home blood pressure monitoring: ≥135/85 mmHg 2, 3
• 24-hour ambulatory monitoring: ≥130/80 mmHg 2, 3

This step prevents overtreatment of white coat hypertension and ensures accurate diagnosis. 2

Lifestyle Modifications (Initiate Immediately for All Patients)

Implement these evidence-based interventions alongside pharmacotherapy, as they enhance drug efficacy and may reduce medication requirements 1, 3, 4:

• Dietary sodium restriction: <2,300 mg/day (ideally <1,500 mg/day) 1, 3
• DASH eating pattern: 8-10 servings/day of fruits and vegetables, 2-3 servings/day of low-fat dairy products 1, 3
• Potassium supplementation: Through dietary sources 1, 3
• Weight reduction: Target BMI 18.5-24.9 kg/m² if overweight 1, 3
• Physical activity: At least 150 minutes of moderate-intensity aerobic exercise per week 1, 3
• Alcohol moderation: ≤2 drinks/day for men, ≤1 drink/day for women 1, 3
• Smoking cessation: For all patients 1, 3

Pharmacological Therapy Algorithm

For Blood Pressure 130-150/80-90 mmHg (Stage 1):

Start with a single first-line agent if the patient has high cardiovascular risk (established CVD, chronic kidney disease, diabetes, or 10-year ASCVD risk ≥10%) 1, 3:

First-line drug classes (choose one): 1, 3, 4

• ACE inhibitors (e.g., lisinopril 10 mg daily) 5
• ARBs (angiotensin receptor blockers)
• Thiazide-like diuretics (chlorthalidone preferred over hydrochlorothiazide due to superior cardiovascular outcomes) 1, 3
• Dihydropyridine calcium channel blockers (e.g., amlodipine)

The European guidelines suggest considering a 3-6 month trial of lifestyle modifications alone for low-to-moderate risk patients with Grade 1 hypertension, but the 2024 ESC guidelines now recommend simultaneous lifestyle advice and pharmacotherapy for office BP ≥140/90 mmHg. 1 In clinical practice, do not delay pharmacotherapy if cardiovascular risk is elevated. 1, 3

For Blood Pressure ≥150/90 mmHg or ≥160/100 mmHg (Stage 2):

Initiate two-drug combination therapy immediately from different classes, preferably as a single-pill combination to improve adherence 1, 2, 3:

Preferred two-drug combinations: 1, 2, 3

• RAS blocker (ACE inhibitor or ARB) + dihydropyridine calcium channel blocker
• RAS blocker (ACE inhibitor or ARB) + thiazide/thiazide-like diuretic

Specific dosing example for Stage 2: 3

• Chlorthalidone 12.5-25 mg daily + lisinopril 10 mg daily, OR
• Chlorthalidone 12.5-25 mg daily + amlodipine 5 mg daily

Two-drug initiation achieves blood pressure control faster and reduces cardiovascular risk more rapidly than sequential monotherapy titration. 3

Special Population Considerations

Black Patients:

Initial therapy should include ARB + dihydropyridine calcium channel blocker OR calcium channel blocker + thiazide-like diuretic due to reduced response to ACE inhibitors as monotherapy. 1, 3

Patients with Diabetes:

Use ACE inhibitor or ARB as first-line therapy to reduce risk of progressive kidney disease. 1, 2, 3

Patients with Chronic Kidney Disease or Albuminuria (UACR ≥30 mg/g):

Initial treatment should include ACE inhibitor or ARB to reduce risk of progressive kidney disease. 1, 2, 3

Patients with Coronary Artery Disease:

Use ACE inhibitor or ARB as first-line therapy; add beta-blocker if history of myocardial infarction, active angina, or heart failure with reduced ejection fraction. 1, 3

Patients with Heart Failure:

Beta-blockers are indicated in addition to ACE inhibitors or ARBs. 1

Pregnant Women or Those Planning Pregnancy:

ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, and direct renin inhibitors are absolutely contraindicated due to fetal injury and death. 1, 3 Use calcium channel blockers or methyldopa instead. 3

Blood Pressure Targets

• Most adults <65 years: <130/80 mmHg 2, 3, 4
• Adults ≥65 years: Systolic <130 mmHg if well-tolerated (range 130-139 mmHg acceptable) 2, 3
• Patients with diabetes, CKD, or established CVD: <130/80 mmHg 2, 3

The ACC/AHA guidelines define hypertension as ≥130/80 mmHg with a treatment target <130/80 mmHg for all patients, while the ESC/ESH guidelines define hypertension as ≥140/90 mmHg with more flexible targets (120-129/<80 mmHg for most, but 130-139 mmHg acceptable in older adults). 6, 2 In practice, target systolic 120-129 mmHg for most adults when well-tolerated. 2

Monitoring and Follow-Up

• Recheck blood pressure in 1 month after initiating therapy 3
• Monitor serum creatinine and potassium 7-14 days after starting or adjusting doses of ACE inhibitors, ARBs, or diuretics 1, 3
• Watch for hyperkalemia with ACE inhibitors/ARBs (especially when combined with diuretics or in patients with CKD) 1, 2
• Watch for hypokalemia with thiazide diuretics 1
• Titrate to full dose of initial agent before adding a second drug if starting with monotherapy 1, 3

Common Pitfalls to Avoid

• Do not delay pharmacotherapy for a prolonged lifestyle modification trial in patients with BP ≥140/90 mmHg and high cardiovascular risk 1, 3
• Avoid hydrochlorothiazide when chlorthalidone or indapamide are available, as longer-acting thiazide-like diuretics have superior cardiovascular outcomes 1
• Do not use beta-blockers as initial therapy unless a specific indication exists (heart failure, coronary disease, recent MI) 6, 1
• Never combine ACE inhibitors and ARBs together, as this increases adverse effects without additional benefit 2
• Avoid ACE inhibitors in patients with history of angioedema or severe bilateral renal artery stenosis 3
• Use thiazides cautiously in patients with gout unless on uric acid-lowering therapy 3

Titration Strategy if Blood Pressure Not Controlled

1. Increase initial agent to full dose (e.g., lisinopril from 10 mg to 20-40 mg daily) 1, 5
2. Add a second agent from a different class if starting with monotherapy 1, 3
3. Escalate to three-drug combination (ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic) if BP remains uncontrolled 1
4. Add spironolactone 25 mg daily for resistant hypertension (BP ≥140/90 mmHg despite three optimized drugs including a diuretic) 1, 2