Why are Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) less effective in treating hypertension in African Americans?

Why ACE Inhibitors and ARBs Are Less Effective in African Americans

In African Americans with hypertension but without heart failure or chronic kidney disease, ACE inhibitors and ARBs are less effective as monotherapy and should not be used as first-line treatment; instead, a thiazide-type diuretic or calcium channel blocker should be initiated. 1

Physiological Basis for Reduced Efficacy

The reduced efficacy of ACE inhibitors and ARBs in African Americans is primarily due to:

• Lower baseline renin-angiotensin system activity - African Americans typically have lower plasma renin activity compared to non-African Americans 2
• Different pathophysiology of hypertension - African American hypertension is often characterized by:
  • Greater salt sensitivity
  • Volume expansion
  • Lower renin levels
  • Different vascular reactivity 1, 2

Evidence from Major Clinical Trials

The ALLHAT trial, which included more than 15,000 Black participants, demonstrated that:

• ACE inhibitors were less effective in lowering blood pressure than either thiazide-type diuretics or calcium channel blockers 1
• This reduced efficacy was associated with:
  • 40% greater risk of stroke
  • 32% greater risk of heart failure
  • 19% greater risk of cardiovascular disease in those randomized to ACE inhibitors versus diuretics 1

Increased Risk of Side Effects

African Americans experience higher rates of adverse effects with ACE inhibitors:

• 3-4 fold higher risk of angioedema compared to white patients 1, 2
• More frequent ACE inhibitor-induced cough 1, 2

Effective Treatment Approaches

First-Line Treatment

• Thiazide-type diuretics (particularly chlorthalidone) or calcium channel blockers are recommended as initial therapy for African Americans without complicating conditions 1, 2

Combination Therapy

• The addition of a thiazide diuretic to an ACE inhibitor or ARB eliminates the racial differences in blood pressure response 1, 2
• Two or more antihypertensive medications are often needed to achieve BP target of less than 130/80 mm Hg in African Americans 1

Special Circumstances

• In African Americans with chronic kidney disease and proteinuria, an ACE inhibitor or ARB should be included in the treatment regimen 2
• For those with heart failure, standard guideline-directed therapy including ACE inhibitors or ARBs is appropriate 1, 2

Practical Recommendations

1. Start with a thiazide diuretic or calcium channel blocker as first-line therapy for African American patients with uncomplicated hypertension
2. If using an ACE inhibitor or ARB is necessary (due to comorbid conditions):
   • Always combine with a thiazide diuretic
   • Monitor closely for side effects, particularly angioedema
   • Consider higher doses may be needed for efficacy 2, 3
3. For resistant hypertension, consider triple therapy with ACE inhibitor/ARB + CCB + diuretic 2

Common Pitfalls to Avoid

• Starting with ACE inhibitors or ARBs as monotherapy in African Americans
• Underdosing thiazide diuretics (doses lower than 12.5-25 mg/day of chlorthalidone may reduce efficacy)
• Simultaneous use of ACE inhibitors and ARBs (not recommended and potentially harmful)
• Failing to intensify therapy when needed (most patients will require multiple agents)

By understanding these racial differences in drug response and following evidence-based treatment algorithms, clinicians can optimize blood pressure control and reduce the disproportionate burden of hypertension-related complications in African American patients.