Aren't Angiotensin Receptor Blockers (ARBs) less likely to cause skin adverse side effects than Angiotensin-Converting Enzyme (ACE) inhibitors?

ARBs Have Fewer Skin-Related Adverse Effects Than ACE Inhibitors

Yes, Angiotensin Receptor Blockers (ARBs) are less likely to cause skin adverse side effects than Angiotensin-Converting Enzyme (ACE) inhibitors. 1

Mechanism Behind the Difference

The difference in skin-related adverse effects between these two medication classes can be explained by their distinct mechanisms of action:

• ACE Inhibitors:

  • Block the conversion of angiotensin I to angiotensin II
  • Also inhibit the breakdown of bradykinin
  • The accumulation of bradykinin is responsible for many of the skin-related adverse effects 1
  • Up to 20% of patients experience ACE inhibitor-induced cough 1
  • Angioedema occurs in <1% of patients (more frequently in Black patients) 1
  • Other skin reactions include rash and taste disturbances 1

• ARBs:

  • Block angiotensin II receptors directly
  • Do not inhibit kininase and therefore have minimal effect on bradykinin levels 1
  • Associated with much lower incidence of cough and angioedema 1, 2

Comparative Risk Data

• A large retrospective cohort study found that compared to β-blockers:

  • ACE inhibitors had a hazard ratio of 3.04 for angioedema
  • ARBs had a hazard ratio of only 1.16 for angioedema 3

• The cumulative incidence of angioedema per 1000 persons was:

  • 1.79 cases for ACE inhibitors
  • 0.62 cases for ARBs 3

• Overall withdrawal rates due to adverse events are lower with ARBs than with ACE inhibitors 4, 5

Clinical Recommendations

1. For patients with history of ACE inhibitor-induced skin reactions:

   • ARBs are recommended as an alternative therapy 1
   • The American College of Cardiology/American Heart Association guidelines specifically recommend ARBs for patients who are ACE inhibitor intolerant due to cough or angioedema 1

2. For patients with history of angioedema:

   • While ARBs are generally safer, there is still a modest risk (2-17%) of recurrent angioedema in patients who experienced angioedema with ACE inhibitors 1
   • Caution is advised when substituting an ARB in patients with previous ACE inhibitor-induced angioedema 1

3. Monitoring considerations:

   • Both medication classes require monitoring of blood pressure, renal function, and potassium levels 1
   • When initiating ARBs, blood pressure (including postural changes), renal function, and potassium should be reassessed within 1-2 weeks 1

Important Caveats

• Despite fewer skin-related adverse effects, ARBs can still cause:

  • Hypotension
  • Renal dysfunction
  • Hyperkalemia 1
  • Rare cases of angioedema 1

• The decision to use an ARB instead of an ACE inhibitor should consider:

  • Patient's risk factors for skin reactions
  • Previous adverse reactions to ACE inhibitors
  • Potential benefit vs. harm in the context of the patient's cardiovascular condition 1

• ARBs are contraindicated in pregnancy (category D) 6

• Combination therapy with both an ACE inhibitor and an ARB is generally not recommended due to increased risk of adverse effects without significant additional benefits 6