November 1st, 2010

Mind the Gap: Real-World ACE Inhibitor Cough Much More Common Than Listed on Labels

The real-world incidence of ACE inhibitor-associated cough is much higher than the reported rate on drug labels and printed in the Physicians’ Desk Reference, according to a study published in the American Journal of Medicine. Sripal Bangalore and colleagues analyzed data from 125 published studies with ACE inhibitors including almost 200,000 patients. They found that the pooled weighted incidence of cough for enalapril was 11.48%, compared with the 1.3% rate reported on the drug’s label. The pooled weighted withdrawal rate due to cough was 2.57% in the trials compared with 0.1% on the label. They also found that although the reported cough rates of different ACE inhibitors vary widely on the labels, in trials the incidence of cough is similar across all the ACE inhibitors.

The authors conclude: “Action must be taken to ensure that the drug labeling is regularly updated both for safety and for medication-specific adverse effects.”

6 Responses to “Mind the Gap: Real-World ACE Inhibitor Cough Much More Common Than Listed on Labels”

  1. As a pulmonologist with special interest in cough I can confirm the data. 1992 Israili published a metaanalysis in Ann Int Med with remarkably similar frequencies. Moreover, ACEI withdrawals could be even more common in routine care as compared with trials. Routine patients use the drug much longer, hence they get a chronic cough more frequently, often after years of use. The ratio female/male is at least 2:1.

    Competing interests pertaining specifically to this post, comment, or both:

  2. Victor I Galvez, MD says:

    My experince show that Captopril has the the more frecuently cough problem

  3. thomas augustine, MD says:

    interesting the way the cough sometimes has a longer lag period from beginning the drug in some folks than in other folks

  4. David Powell , md, facc says:

    More common in African Americans and females and? Asians? Why?

  5. Howard Holtz, MD says:

    Switching to AT blocker is usual practice for ACE cough but occasional patients cough with AT blockers as well. Had a patient recently who coughed on ACEinh as well as AT blocker. Did not cough when I made the second switch to aliskiren (Tekturna).

    Competing interests pertaining specifically to this post, comment, or both:

  6. Estimated incidence of cough with ACE inhibitors varies greatly (5-20%), which means that from one in twenty to one in five patients would have this kind of cough. Every physician may have one´s own experience. My experience of seeing about 1300 patients at internal dpt. yearly for five consecutive years with great proportion of them being on ACE inhibitors is that the incidence is not as high as about 15% incidence (this number was mostly promoted by ARB companies). Had every fifth patient to switch to ARB, I would prefer administering ARB right from the start. Not every cough is truly ACE-inhibitor associated. (In Slovakia, there was a period when patients had to pay much money for ARBs and G.P.s switched them back to ACE-inhibitors and when these pts. later had no cough on ACE-inhibitors, therefore probably quite different reason for their cough back in the history.)
    I agree with the above mentioned time-lag for occurrence of ACE-inhibitor induced cough.
    With regards,
    Milan Kostek, MD
    One of the numerous papers covering this topic as well:
    David B. Matchar et al.: Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension
    Ann Intern Med. 2008;148:16-29.
    The observed rates of cough were much higher in randomized, controlled trials, in which patients were queried systematically for the symptom, than those in cohort studies. The rates of cough in randomized, controlled trials were 9.9% for the ACE inhibitor group and 3.2% for the ARB group (absolute risk difference, 6.7 percentage points), whereas the rates of cough in cohort studies were 1.7% for the ACE inhibitor group and 0.6% for the ARB group (absolute risk difference, 1.1 percentage points).

    Competing interests pertaining specifically to this post, comment, or both:
    none, solely my personal experience