What are the initial and subsequent treatment recommendations for managing hypertension?

Hypertension Management

Initial Treatment Strategy

For most adults with confirmed hypertension (BP ≥140/90 mmHg), initiate both lifestyle modifications AND pharmacological therapy simultaneously—do not delay medication while attempting lifestyle changes alone. 1, 2

Confirming the Diagnosis

Before starting treatment, confirm hypertension using out-of-office measurements: 3

• Home BP monitoring: ≥135/85 mmHg
• 24-hour ambulatory BP monitoring: ≥130/80 mmHg

Initial Pharmacological Approach

The choice of initial therapy depends on baseline BP level:

For BP 140-159/90-99 mmHg (Grade 1):

• Consider starting with a single agent (ACE inhibitor, ARB, thiazide-like diuretic, or calcium channel blocker) 2, 3
• However, the 2024 ESC guidelines favor starting with two-drug combination therapy even at this level for faster BP control 2

For BP ≥160/100 mmHg (Grade 2) or BP ≥150/90 mmHg:

• Start with two-drug combination therapy from different classes 1, 2, 4
• Preferred combinations: 1, 2
  • RAS blocker (ACE inhibitor or ARB) + calcium channel blocker, OR
  • RAS blocker + thiazide/thiazide-like diuretic
• Use single-pill combinations when possible to improve adherence 2, 3

Specific First-Line Medication Recommendations

Standard initial regimen for non-Black patients: 2

• Lisinopril 10 mg daily (ACE inhibitor) PLUS
• Amlodipine 5 mg daily (calcium channel blocker), OR
• Chlorthalidone 12.5-25 mg daily (thiazide-like diuretic)

Note: Chlorthalidone is strongly preferred over hydrochlorothiazide due to longer half-life and superior cardiovascular outcomes data 2, 4

For Black patients: 1, 2

• Initial therapy should include a diuretic or calcium channel blocker, either alone or combined with a RAS blocker
• Preferred: ARB + calcium channel blocker OR calcium channel blocker + thiazide-like diuretic
• Black patients have reduced response to ACE inhibitors as monotherapy

Lifestyle Modifications (Implement Simultaneously with Medications)

All patients with BP >120/80 mmHg should receive comprehensive lifestyle counseling: 2, 4, 5

• Weight loss: For overweight individuals through caloric restriction 2
• DASH diet: Emphasizing 8-10 servings/day of fruits and vegetables, 2-3 servings/day of low-fat dairy 2, 4
• Sodium restriction: <2,300 mg/day 2, 5
• Increased potassium intake: Through dietary sources 2
• Physical activity: At least 150 minutes of moderate-intensity aerobic exercise per week 2, 5
• Alcohol moderation: ≤2 drinks/day for men, ≤1 drink/day for women 2, 5
• Smoking cessation: For all patients 2

The BP-lowering effects of lifestyle modifications are additive and enhance pharmacologic therapy efficacy 4

Target Blood Pressure Goals

For most adults <65 years: 1, 2, 3

• Target systolic BP: 120-129 mmHg
• Target diastolic BP: <80 mmHg
• Provided treatment is well tolerated

For adults ≥65 years: 2, 3

• Target systolic BP: 130-139 mmHg (more conservative due to tolerability)

Special populations:

• Diabetes: 130-139 mmHg systolic 3
• CKD with eGFR >30 mL/min/1.73m²: 120-129 mmHg systolic 1, 3
• History of stroke/TIA: 120-130 mmHg systolic 1

Medication Titration and Escalation

Step 2: If BP Not Controlled on Two Drugs

Increase to full doses before adding third agent: 2

• Lisinopril can be titrated from 10 mg to 20-40 mg daily 2, 6
• Amlodipine can be increased to 10 mg daily
• Chlorthalidone can be increased to 25 mg daily

Step 3: Add Third Drug (Three-Drug Combination)

Standard three-drug regimen: 2

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

Step 4: Resistant Hypertension Management

Definition: BP ≥140/90 mmHg despite appropriate lifestyle management plus three antihypertensive drugs (including a diuretic) at adequate doses 3

Before diagnosing resistant hypertension, rule out: 3

• White coat hypertension
• Medication nonadherence
• Secondary causes of hypertension

Treatment algorithm for resistant hypertension: 1, 2

1. First-line addition: Spironolactone 25 mg daily (mineralocorticoid receptor antagonist) 1, 2

   • Most effective fourth-line agent
   • Monitor serum creatinine and potassium closely 3

2. If spironolactone not tolerated or contraindicated: 1

   • Eplerenone (alternative MRA), OR
   • Amiloride (potassium-sparing diuretic), OR
   • Higher-dose thiazide/thiazide-like diuretic, OR
   • Loop diuretic

3. Fifth-line options: 1

   • Bisoprolol (beta-blocker), OR
   • Doxazosin (alpha-blocker)

4. Additional options if still uncontrolled: 1

   • Centrally acting agents
   • Hydralazine (direct vasodilator)

5. Renal denervation: May be considered in high-volume centers after multidisciplinary assessment for patients uncontrolled on three-drug combination 1

Special Population Considerations

Coronary Artery Disease

• ACE inhibitors or ARBs are recommended as first-line therapy 2

Albuminuria (UACR ≥30 mg/g)

• ACE inhibitor or ARB must be included in initial treatment to reduce progressive kidney disease 2, 3
• RAS blockers are more effective at reducing albuminuria than other agents 1

Heart Failure with Reduced Ejection Fraction (HFrEF)

• ACE inhibitor (or ARB if ACE inhibitor not tolerated) + beta-blocker + MRA + SGLT2 inhibitor 1
• Diuretics as needed for volume management

Heart Failure with Preserved Ejection Fraction (HFpEF)

• SGLT2 inhibitors are recommended to improve outcomes 1
• ARBs and/or MRAs may be considered if BP above target 1

Pregnancy or Planning Pregnancy

• Absolute contraindications: ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, direct renin inhibitors 2, 3
• Use methyldopa, nifedipine, or labetalol instead 1

Monitoring and Follow-Up

Initial follow-up: 2

• Recheck BP in 1 month after initiating or changing therapy
• Goal: Achieve BP control within 3 months 2

Laboratory monitoring when using RAS blockers or MRAs: 2, 3

• Check serum creatinine and potassium 7-14 days after initiation or dose changes
• Increased hyperkalemia risk when combining MRAs with ACE inhibitors/ARBs 3

When using diuretics: 2

• Monitor for hypokalemia

Common Pitfalls to Avoid

• Do NOT delay pharmacotherapy for a trial of lifestyle modification alone in patients with BP ≥140/90 mmHg 2
• Avoid hydrochlorothiazide when chlorthalidone or indapamide are available (inferior outcomes data) 2
• Do NOT use beta-blockers as initial therapy unless specific indication exists (heart failure, coronary disease, post-MI) 2
• Never combine ACE inhibitor + ARB together—increases adverse effects without additional benefit 3
• Avoid ACE inhibitors/ARBs in severe bilateral renal artery stenosis (risk of acute renal failure) 2
• Use thiazides cautiously in patients with gout unless on uric acid-lowering therapy 2