Why are Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) less effective in individuals with dark skin?

Why ACE Inhibitors and ARBs Are Less Effective in Individuals with Dark Skin

ACE inhibitors and ARBs are less effective as monotherapy in Black patients due to lower baseline renin-angiotensin system activity, requiring combination with diuretics for optimal efficacy. 1, 2

Physiological Basis for Reduced Efficacy

The reduced effectiveness of ACE inhibitors and ARBs in Black patients is primarily due to:

1. Lower baseline renin-angiotensin system activity:

   • Black patients typically have lower plasma renin activity compared to non-Black patients
   • This results in a blunted response to medications that target this system 1

2. Differences in blood pressure regulation:

   • Black patients often have more volume-dependent hypertension
   • Salt sensitivity is more prevalent in this population 1, 2

Clinical Evidence

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) provides clear evidence:

• Monotherapy with beta-blockers, ACE inhibitors, or ARBs lowers blood pressure to a lesser degree in Black patients than in white patients 1
• In the ALLHAT trial with over 15,000 Black participants, 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 Black patients randomized to ACE inhibitors versus diuretics 1

Overcoming Reduced Efficacy

The racial differences in blood pressure-lowering efficacy can be effectively addressed by:

• Combination therapy: Adding a thiazide diuretic to an ACE inhibitor or ARB eliminates the interracial differences in blood pressure response 1, 2
• First-line recommendations: For Black patients with hypertension, guidelines recommend starting with:
  • Thiazide-type diuretics (particularly chlorthalidone)
  • Calcium channel blockers 2

Additional Considerations

Side Effect Profile

Black patients also experience different side effect profiles with these medications:

• Higher risk of angioedema: Black patients have a 3-4 fold higher risk of angioedema with ACE inhibitors compared to white patients 1, 2
• Increased cough: Black patients may experience more cough attributed to ACE inhibitors 1
• ARBs as alternatives: ARBs may be preferred over ACE inhibitors in Black patients due to lower risk of angioedema 2

Special Populations

Despite reduced efficacy as monotherapy, ACE inhibitors and ARBs still have important roles in specific Black patient populations:

• Chronic kidney disease with proteinuria: Adding an ACE inhibitor or ARB to the regimen is recommended 2
• Diabetic nephropathy: Greater preservation of renal function was observed in Black patients with hypertensive nephrosclerosis treated with ACE inhibitor-containing regimens compared to beta-blockers or calcium antagonists 1

Practical Recommendations

For optimal management of hypertension in Black patients:

1. Initial therapy:

   • Start with thiazide diuretics or calcium channel blockers
   • Consider chlorthalidone 12.5 mg daily or amlodipine 5 mg daily 2

2. When ACE inhibitors/ARBs are needed:

   • Always combine with a thiazide diuretic
   • Monitor closely for side effects, particularly angioedema
   • Consider ARBs over ACE inhibitors if angioedema is a concern 2

3. For resistant hypertension:

   • Triple therapy with ACE inhibitor/ARB + CCB + diuretic may be needed 2

4. Target blood pressure:

   • Aim for <130/80 mmHg in most Black patients with hypertension 2

By understanding these racial differences in drug response and implementing appropriate treatment strategies, clinicians can optimize blood pressure control and reduce cardiovascular risk in Black patients.