Can losartan (angiotensin II receptor antagonist) cause angioedema?

Losartan Can Cause Angioedema, Though Less Frequently Than ACE Inhibitors

Yes, losartan and other angiotensin II receptor blockers (ARBs) can cause angioedema, though the risk is significantly lower than with ACE inhibitors.

Risk of Angioedema with ARBs vs ACE Inhibitors

• ACE inhibitors cause angioedema in approximately 0.3% of patients (95% CI: 0.28-0.32) 1
• ARBs like losartan have a much lower incidence of angioedema:
  • Incidence with ARBs is 0.11% (95% CI: 0.09-0.13), which is not significantly different from placebo (0.07%; 95% CI: 0.05-0.09) 1
  • The FDA label for losartan specifically lists angioedema as a reported postmarketing adverse reaction 2

Mechanism of Action and Angioedema Risk

• ACE inhibitors vs ARBs mechanism difference:
  • ACE inhibitors block bradykinin degradation (primary mechanism of angioedema)
  • ARBs block angiotensin II receptors without directly affecting bradykinin 3
• This mechanistic difference explains why ARBs have a lower risk of angioedema

Cross-Reactivity Risk

• Patients with previous ACE inhibitor-induced angioedema have a 2-17% risk of recurrent angioedema when switched to an ARB 3
• Multiple case reports document angioedema occurring with losartan in patients with and without prior ACE inhibitor-induced angioedema 4, 5, 6
• Some cases occurred within 24 hours of starting losartan, while others developed up to 16 months after initiation 5

Clinical Implications and Management

• For patients with a history of ACE inhibitor-induced angioedema who require RAAS blockade:

  • Wait at least 6 weeks after discontinuing the ACE inhibitor before starting an ARB 3
  • Start with the lowest effective dose of losartan (25-50 mg daily) and titrate cautiously 3
  • Monitor closely during initial dosing and educate patients about early signs of angioedema

• Never rechallenge with an ACE inhibitor after angioedema, as this is potentially life-threatening 3

Special Considerations

• Case reports suggest women may be more susceptible to losartan-induced angioedema (11 of 13 cases in one series were women) 5
• Patients with renal compromise may be at higher risk for ARB-induced angioedema 7
• Angioedema can affect the face, lips, tongue, and larynx, potentially causing airway obstruction 2

Documentation and Monitoring

• Document any angioedema reaction prominently in the patient's medical record 3
• Patients experiencing angioedema with losartan should discontinue the medication immediately and seek medical attention
• Alternative antihypertensive classes with no known cross-reactivity include calcium channel blockers, thiazide diuretics, and beta-blockers 3

While losartan is generally considered safer than ACE inhibitors regarding angioedema risk, clinicians should remain vigilant about this potentially life-threatening adverse effect, especially in patients with a history of ACE inhibitor-induced angioedema.