Cough associated with the use of ACE inhibitors

This is a dry, irritating cough that is associated with the use of ACE inhibitors. There is no specific treatment.

• the mechanism of the cough associated with ACE-I is unrelated to the inhibition of the renin-angiotensin system because treatment with either angiotensin receptor blockers or renin inhibitors does not cause similar problems (1)
  • a possible mechanism is the accumulation of bradykinins or tachykinins in the airways with consequent stimulation of vagal afferents that subserve the cough reflex, particularly the nonmyelinated or C fibers
    • this theory is supported by Lalloo et al. (2) who postulated that ACE-I-related cough probably results from inhibition of the degradation of kinins, particularly bradykinin in the airways

Data about the incidence of cough associated with ACE inhibitors are conflicting (1)

• has been reported to be as low as 1-2% in retrospective or postmarketing studies. Highs of 37-39% have been reported in controlled trials
• in a study using a dechallenge and rechallenge method, the incidence of cough was compared for four different ACE inhibitors (1)
  • the cough incidence were as follows:
    • (1) Cilazapril 22.86%
    • (2) Enalapril 21.95%
    • (3) Perindopril 10.96%
    • (4) Imidapril 13.16% .

With respect to resolution of the cough and continuation of ACEI treatment, a lower dose may be tolerated but it may be necessary to withdraw the drug; switching to another ACE inhibitor is unlikely to help.

Notes:

• asthma
  • ACEIs - symptoms of airway obstruction in relation to treatment with angiotensin converting enzyme inhibitors seem to be a rare but potentially serious reaction generally occurring within the first few weeks of treatment (3,4)

Reference:

• 1) Tumanan-Mendoza BA et al. Dechallenge and rechallenge method showed different incidences of cough among four ACE-Is. J Clin Epidemiol. 2007 Jun;60(6):547-53. Epub 2006 Oct 25.
• 2) Lalloo UG et al. Pathophysiology and clinical presentation of cough. J Allergy Clin Immunol 1996; S91-S96.
• 3) John Rees, Dipak Kanabar, Shriti Pattani. ABC of Asthma, 6th Edition
• 4) Lunde H et al. Dyspnoea, asthma, and bronchospasm in relation to treatment with angiotensin converting enzyme inhibitors. BMJ. 1994 Jan 1;308(6920):18-21.
• 5) Drug & Therapeutic Bulletin 1995; 33(1):1-3.