What are alternative medications to thiazides (thiazide diuretics) for hypertension management?

Alternative Medications to Thiazide Diuretics for Hypertension Management

Calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) are the primary alternative medications to thiazide diuretics for hypertension management. These drug classes have demonstrated effectiveness in blood pressure control and cardiovascular risk reduction, making them suitable alternatives when thiazides are not appropriate 1.

First-Line Alternative Options

Calcium Channel Blockers (CCBs)

• Dihydropyridines:

  • Amlodipine (2.5-10 mg daily)
  • Felodipine (2.5-10 mg daily)
  • Nifedipine LA (30-90 mg daily)
  • Isradipine (5-10 mg twice daily)
  • Nicardipine SR (60-120 mg twice daily)

• Non-dihydropyridines:

  • Diltiazem ER (120-360 mg daily)
  • Verapamil SR (120-360 mg once or twice daily)

• Considerations:

  • Preferred first-line agents for Black patients 1
  • Associated with dose-related pedal edema, more common in women 1
  • Avoid in heart failure with reduced ejection fraction (HFrEF) 1

ACE Inhibitors

• Options:

  • Lisinopril (10-40 mg daily)
  • Ramipril (2.5-20 mg daily or twice daily)
  • Benazepril (10-40 mg daily)
  • Fosinopril (10-40 mg daily)
  • Perindopril (4-16 mg daily)

• Considerations:

  • Preferred for non-Black patients 2
  • Reduce mortality and cardiovascular events 3
  • Contraindicated in pregnancy 1
  • Risk of angioedema and hyperkalemia 1
  • Beneficial in patients with proteinuria or diabetic nephropathy 4

Angiotensin Receptor Blockers (ARBs)

• Options:

  • Losartan (50-100 mg daily or twice daily)
  • Valsartan (80-320 mg daily)
  • Olmesartan (20-40 mg daily)
  • Candesartan (8-32 mg daily)
  • Irbesartan (150-300 mg daily)

• Considerations:

  • Alternative for patients who develop ACE inhibitor-induced cough 1
  • Similar efficacy to ACE inhibitors 1
  • Contraindicated in pregnancy 1
  • Risk of hyperkalemia in chronic kidney disease 1
  • Beneficial in diabetic nephropathy 4

Second-Line Alternative Options

Beta-Blockers

• Cardioselective:

  • Metoprolol succinate (50-200 mg daily)
  • Bisoprolol (2.5-10 mg daily)
  • Atenolol (25-100 mg twice daily)

• With Vasodilatory Properties:

  • Nebivolol (5-40 mg daily)
  • Carvedilol (12.5-50 mg twice daily)

• Considerations:

  • Not recommended as first-line unless patient has ischemic heart disease or heart failure 1
  • Less effective in reducing stroke compared to other agents 5
  • May cause fatigue, sexual dysfunction, and mask hypoglycemia symptoms 1

Aldosterone Antagonists

• Options:

  • Spironolactone (25-100 mg daily)
  • Eplerenone (50-100 mg daily or twice daily)

• Considerations:

  • Effective add-on therapy for resistant hypertension 2
  • Preferred in primary aldosteronism 1
  • Risk of hyperkalemia, especially with renal dysfunction 1
  • Spironolactone associated with gynecomastia and impotence 1

Special Populations and Considerations

Chronic Kidney Disease

• Preferred agents: ACE inhibitors or ARBs 2
• For GFR <30 mL/min: Loop diuretics preferred over thiazides 1

Heart Failure

• Preferred agents:
  • ACE inhibitors or ARBs
  • Beta-blockers (specifically bisoprolol, metoprolol succinate, carvedilol)
  • Aldosterone antagonists 1

Elderly Patients

• Preferred agents: CCBs or ARBs due to better tolerability 1
• Caution with: Alpha-blockers due to orthostatic hypotension risk 1

Metabolic Syndrome/Diabetes

• Preferred agents: ACE inhibitors or ARBs 1
• Avoid: Combination of beta-blockers and thiazides due to increased risk of new-onset diabetes 1

Combination Therapy

When monotherapy is insufficient, these effective combinations should be considered 1:

• CCB + ACE inhibitor
• CCB + ARB
• CCB + thiazide diuretic
• ACE inhibitor + thiazide diuretic
• ARB + thiazide diuretic

Clinical Pearls

• The choice of antihypertensive should be guided by comorbidities, demographic factors, and potential side effects 1
• Most patients will require more than one drug to achieve blood pressure goals 4
• Fixed-dose combinations can improve adherence by reducing pill burden 1
• Monitoring for adverse effects is essential, particularly electrolyte abnormalities with diuretics and hyperkalemia with ACE inhibitors/ARBs 1
• The primary goal is blood pressure reduction rather than the specific agent used, as this is what drives cardiovascular risk reduction 4

Common Pitfalls to Avoid

• Underutilizing CCBs in Black patients, where they are more effective than ACE inhibitors or ARBs 1
• Combining ACE inhibitors with ARBs, which increases adverse effects without additional benefit 1
• Using beta-blockers as first-line therapy in uncomplicated hypertension 3
• Failing to adjust therapy based on patient response and tolerability 2
• Neglecting to monitor renal function and electrolytes when using ACE inhibitors, ARBs, or diuretics 1