Is lisinopril a better first-line antihypertensive than amlodipine?

Lisinopril vs. Amlodipine as First-Line Antihypertensive Therapy

Neither lisinopril nor amlodipine is clearly superior as a first-line antihypertensive agent, as both medications have similar efficacy for the primary outcome of reducing cardiovascular morbidity and mortality, though they have different strengths in specific patient populations.

Comparative Efficacy

• The ALLHAT trial, one of the largest hypertension trials to date, demonstrated no significant difference between lisinopril and amlodipine in the primary outcome of fatal coronary heart disease or nonfatal myocardial infarction 1
• Amlodipine showed better systolic and diastolic blood pressure reduction compared to lisinopril in some studies, particularly at 24 hours post-dose (-20/-14 mmHg vs -11/-7 mmHg) 2
• Amlodipine provides more consistent 24-hour blood pressure control compared to lisinopril, which shows greater effect during daytime hours 2

Patient-Specific Considerations

Race

• Lisinopril is less effective than diuretics or calcium channel blockers in Black patients for reducing combined cardiovascular endpoints and stroke 1
• Amlodipine is particularly effective in Black patients for preventing heart failure and stroke compared to ACE inhibitors 3

Comorbid Conditions

• Diabetes and Kidney Disease:

  • ACE inhibitors like lisinopril are renoprotective in patients with type 2 diabetes mellitus 1, 4
  • In patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the development of end-stage renal disease 5
  • Lisinopril reduces urinary albumin excretion more effectively than calcium channel blockers, suggesting additional renoprotective benefits 6

• Heart Failure:

  • Amlodipine had a higher risk for heart failure than chlorthalidone in the ALLHAT study (RR 1.38; 95% CI 1.25 to 1.52) 1
  • Lisinopril also showed increased risk of heart failure compared to chlorthalidone, but to a lesser degree than amlodipine (RR 1.19; 95% CI 1.07 to 1.31) 1

Mechanism of Action and Pharmacology

• Lisinopril inhibits angiotensin-converting enzyme (ACE), reducing angiotensin II and aldosterone levels, leading to vasodilation 7
• Amlodipine blocks calcium influx into vascular smooth muscle cells, causing vasodilation 3
• Lisinopril is excreted unchanged in urine and requires dosage adjustment in renal impairment 8
• Lisinopril bioavailability is approximately 25% and is not significantly affected by food or age 8

Side Effect Profiles

• Lisinopril may cause dry cough, angioedema, and hyperkalemia 7
• Amlodipine's most common side effects include peripheral edema and headache 9
• In patients with hypertension and normal renal function treated with lisinopril alone, the mean increase in serum potassium was approximately 0.1 mEq/L 7

Clinical Recommendations

Based on the evidence reviewed, the following approach is recommended:

1. For general hypertensive population: Either medication is appropriate as first-line therapy based on similar cardiovascular outcomes 1

2. For specific populations:

   • Black patients: Amlodipine is preferred over lisinopril due to better efficacy 1, 3
   • Diabetic patients with proteinuria: Lisinopril is preferred due to renoprotective effects 1, 4
   • Patients with heart failure: Lisinopril is preferred over amlodipine 1

Common Pitfalls and Caveats

• Monotherapy with either agent is often insufficient to reach blood pressure goals; the ALLHAT study showed that on average, patients required two antihypertensive drugs 1
• Blood pressure response to lisinopril varies by race, with Black patients typically showing less response to ACE inhibitors when used as monotherapy 7
• The renoprotective effects of lisinopril may be independent of its blood pressure-lowering effects 4
• While amlodipine may show better 24-hour blood pressure control in some studies, this doesn't necessarily translate to better cardiovascular outcomes 2

In conclusion, the choice between lisinopril and amlodipine should be guided by patient characteristics including race, comorbidities, and potential side effects, as neither medication has demonstrated clear superiority for reducing overall cardiovascular morbidity and mortality as a first-line agent.