What are the latest first-line treatment options for managing hypertension?

Latest First-Line Antihypertensive Medications

The latest first-line treatment options for managing hypertension include thiazide or thiazide-like diuretics (particularly chlorthalidone), angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and dihydropyridine calcium channel blockers, with selection based on patient-specific factors and comorbidities. 1

Initial Approach to Hypertension Management

Blood Pressure Targets

• Most patients: <130/80 mmHg
• Patients 65-79 years: 130-139/80 mmHg
• Patients ≥80 years: 140-150/<80 mmHg 1

Lifestyle Modifications (First-Line for All Patients)

• Sodium restriction (<2,300 mg/day or reduction of at least 1,000 mg/day)
• Increased dietary potassium (3,500-5,000 mg/day)
• Weight loss if overweight/obese
• Physical activity (aerobic or dynamic resistance 90-150 min/week)
• Moderation of alcohol intake (≤2 drinks/day for men, ≤1 drink/day for women)
• DASH-like diet rich in fruits, vegetables, whole grains, and low-fat dairy products 2

Pharmacological Treatment Options

First-Line Medications

1. Thiazide or Thiazide-like Diuretics:

   • Chlorthalidone (12.5-25 mg daily) is preferred due to stronger evidence and longer duration of action 1, 3
   • Hydrochlorothiazide is an alternative but may be less effective 4

2. ACE Inhibitors:

   • Examples: Lisinopril, enalapril, ramipril 5, 6
   • Particularly beneficial for patients with diabetes with albuminuria, heart failure, or post-MI 2

3. Angiotensin Receptor Blockers (ARBs):

   • Examples: Losartan, candesartan, valsartan
   • Alternative to ACE inhibitors when not tolerated (e.g., due to cough) 2, 1
   • Preferred in patients with atrial fibrillation 2

4. Calcium Channel Blockers (Dihydropyridines):

   • Examples: Amlodipine, nifedipine (long-acting)
   • Particularly effective in Black patients 1, 7

Patient-Specific Considerations

Based on Race/Ethnicity:

• Black patients: Thiazide diuretics or calcium channel blockers are more effective as initial therapy 1, 7

Based on Comorbidities:

• Diabetes with albuminuria: ACE inhibitor or ARB is first-line 2
• Heart failure with reduced EF: GDMT beta-blockers, ACE inhibitors or ARBs 2
• Chronic kidney disease: ACE inhibitor or ARB 2
• Atrial fibrillation: ARBs may reduce recurrence 2
• Post-MI or ACS: GDMT beta-blockers 2

Combination Therapy Approach

Most patients with hypertension will require multiple medications to achieve target blood pressure 5, 7:

1. Initial Therapy:

   • For BP 140-159/90-99 mmHg: Start with a single agent
   • For BP ≥160/100 mmHg: Consider starting with two agents 2

2. Combination Recommendations:

   • ACE inhibitor or ARB + thiazide-like diuretic
   • ACE inhibitor or ARB + calcium channel blocker
   • Calcium channel blocker + thiazide-like diuretic 1

3. Combinations to Avoid:

   • ACE inhibitor + ARB
   • ACE inhibitor or ARB + direct renin inhibitor 2

Management of Resistant Hypertension

Resistant hypertension is defined as BP ≥140/90 mmHg despite therapy with three antihypertensive drugs including a diuretic 2.

• Consider adding a mineralocorticoid receptor antagonist (spironolactone) as fourth-line therapy 2, 1
• Triple therapy with ARB + diuretic + calcium channel blocker is recommended before adding a fourth agent 1

Monitoring and Follow-up

• Monitor serum potassium, sodium, and renal function within 1 month of starting therapy 1
• For patients on ACE inhibitors, ARBs, or diuretics: Check serum creatinine/eGFR and potassium at least annually 2
• Check blood pressure control within 3 months of medication changes 1

Important Considerations and Pitfalls

• Fixed-dose combinations improve medication adherence compared to separate pills 1
• Bedtime dosing of at least one antihypertensive medication may improve BP control 2
• Avoid immediate-release nifedipine and hydralazine for non-emergency hypertension management 8
• Be cautious with ACE inhibitors or ARBs in women of childbearing potential due to teratogenic risks 1
• In elderly patients, start with lower doses and titrate more cautiously to avoid adverse effects 1