What are the preferred initial antihypertensive medications, including Angiotensin-Converting Enzyme (ACE) inhibitors, Angiotensin Receptor Blockers (ARBs), Calcium Channel Blockers (CCBs), and beta blockers?

Preferred Antihypertensive Medications: Latest Guidelines

For initial antihypertensive therapy, first-line agents include thiazide-like diuretics, ACE inhibitors, ARBs, and calcium channel blockers, with specific choices based on patient characteristics and comorbidities. 1

First-Line Antihypertensive Medications

• Thiazide-like diuretics (especially chlorthalidone and indapamide) are preferred due to their proven efficacy in reducing cardiovascular events 1
• ACE inhibitors (e.g., ramipril, enalapril) are effective in blood pressure reduction and have shown benefits in preventing cardiovascular outcomes 2, 3
• ARBs provide similar benefits to ACE inhibitors with fewer side effects such as cough, making them particularly valuable in patients who cannot tolerate ACE inhibitors 1
• Dihydropyridine calcium channel blockers (e.g., amlodipine) are effective first-line agents, especially in older patients and Black patients 1

Special Population Considerations

• For patients with diabetes and albuminuria (UACR ≥30 mg/g), an ACE inhibitor or ARB should be the first-line treatment to reduce the risk of progressive kidney disease 1
• For patients with established coronary artery disease, ACE inhibitors or ARBs are recommended as first-line therapy 1
• For Black patients, calcium channel blockers and thiazide diuretics are generally more effective than ACE inhibitors 1
• For patients ≥60 years old, calcium channel blockers or thiazide diuretics are often preferred 1

Combination Therapy Approach

• For patients with blood pressure ≥150/90 mmHg (or ≥160/100 mmHg per some guidelines), initial therapy with two antihypertensive medications is recommended 1
• Preferred combinations include:
  • ACE inhibitor or ARB + calcium channel blocker 1, 4
  • ACE inhibitor or ARB + thiazide-like diuretic 1
• Combinations to avoid:
  • ACE inhibitor + ARB (increases risk of hyperkalemia without additional benefit) 1
  • ACE inhibitor or ARB + direct renin inhibitor 1

Newer Molecules and Considerations

• While there are no truly "new" classes of antihypertensives that have emerged recently as first-line agents, newer formulations of established medications focus on:
  • Single-pill combinations to improve adherence 1
  • Long-acting formulations to provide 24-hour coverage with once-daily dosing 2
  • Mineralocorticoid receptor antagonists (e.g., spironolactone) are increasingly recommended for resistant hypertension when three first-line agents (including a diuretic) fail to control blood pressure 1

Beta Blockers

• Beta blockers are no longer considered preferred first-line agents for uncomplicated hypertension due to less favorable outcomes compared to other classes 1
• They remain indicated for specific conditions:
  • Post-myocardial infarction 2
  • Active angina 1
  • Heart failure with reduced ejection fraction 1

Monitoring and Follow-up

• Monitor serum creatinine and potassium within 7-14 days after initiating ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists, and at least annually thereafter 1
• Watch for hyperkalemia when using ACE inhibitors or ARBs, especially in combination with mineralocorticoid receptor antagonists 1
• ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, direct renin inhibitors, and neprilysin inhibitors are contraindicated in pregnancy and should be avoided in women of childbearing potential who are not using reliable contraception 1

Common Pitfalls to Avoid

• Underdosing medications before adding additional agents 1
• Failing to consider ethnicity in medication selection (ACE inhibitors and ARBs are less effective in Black patients) 1
• Using ACE inhibitor + ARB combinations (increased adverse effects without additional benefit) 1
• Overlooking the need for more aggressive initial therapy (two-drug combinations) in patients with markedly elevated blood pressure 1
• Discontinuing ACE inhibitors or ARBs when GFR declines to <30 mL/min/1.73m² (may still provide cardiovascular benefit) 1