What is the initial medication of choice for treating hypertension?

Initial Medication of Choice for Hypertension

For most patients with hypertension, first-line therapy should include any of the following drug classes: ACE inhibitors, angiotensin receptor blockers (ARBs), thiazide or thiazide-like diuretics, or dihydropyridine calcium channel blockers. 1, 2, 3

Treatment Algorithm Based on Patient Characteristics

1. Initial Selection Based on Patient Demographics:

   • Younger white patients (<55 years): ACE inhibitors or ARBs are generally more effective as first-line agents 1
   • Older white patients (≥55 years) or black patients of any age: Calcium channel blockers or thiazide diuretics are more effective 1, 2
   • Patients with diabetes and albuminuria: ACE inhibitors or ARBs are recommended first-line 1, 2

2. Dosing Considerations:

   • Start with lower doses and titrate up based on blood pressure response
   • For example, with lisinopril, the recommended initial dose is 10 mg once daily, with usual dosage range of 20-40 mg per day 4
   • Allow at least 4 weeks to observe full response before adjusting dosage 1

3. Combination Therapy:

   • For patients with BP ≥160/100 mmHg, consider initiating treatment with two antihypertensive medications 1
   • Logical combinations follow the AB/CD rule: (ACE inhibitor or ARB) + (Calcium channel blocker or Diuretic) 1, 2
   • Fixed-dose combinations may improve medication adherence 1, 2

Special Considerations

• Compelling Indications for Specific Drug Classes:

  • Heart Failure: ACE inhibitors, ARBs, beta-blockers, mineralocorticoid receptor antagonists 2
  • Chronic Kidney Disease: ACE inhibitors or ARBs, especially with albuminuria 1, 2
  • Post-Myocardial Infarction: ACE inhibitors (e.g., lisinopril) 4
  • Benign Prostatic Hyperplasia: Alpha-blockers 1

• Contraindications:

  • Pregnancy: Avoid ACE inhibitors and ARBs due to teratogenic potential 2
  • Renovascular Disease: Caution with ACE inhibitors and ARBs 1
  • Hyperkalemia Risk: Monitor potassium levels with ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists 1

Target Blood Pressure Goals

• General Population: <130/80 mmHg 2, 3
• Older Adults (≥65 years): <130 mmHg systolic 3
• Patients with Diabetes, CKD, or Established CVD: <130/80 mmHg 1, 2

Monitoring and Follow-up

• Monitor blood pressure, renal function, and electrolytes within 2-4 weeks after starting or changing medications 2
• For patients treated with ACE inhibitors, ARBs, or diuretics, check serum creatinine/eGFR and potassium at least annually 1
• Consider resistant hypertension (BP ≥140/90 mmHg despite three medications including a diuretic) if targets not achieved 1

Common Pitfalls to Avoid

1. Inappropriate Drug Selection: Not considering patient demographics and comorbidities when selecting initial therapy
2. Inadequate Dosing: Failing to titrate medication to effective doses
3. Overlooking Lifestyle Modifications: Diet, exercise, and sodium restriction remain fundamental and should accompany pharmacologic therapy 2, 3
4. Medication Combinations: Avoid combining ACE inhibitors with ARBs due to increased adverse effects without additional benefit 2
5. Inadequate Monitoring: Failing to monitor for electrolyte abnormalities, especially with diuretics, ACE inhibitors, or ARBs

The ALLHAT trial, one of the largest hypertension studies, demonstrated that thiazide diuretics were superior to ACE inhibitors and calcium channel blockers in preventing cardiovascular disease and were less expensive, suggesting they should be preferred for first-step therapy in many patients 5. However, more recent guidelines emphasize individualized selection among the four major drug classes based on patient characteristics and comorbidities.