Skip to main content
SpringerLink
Log in

Cough due to ace inhibitors: a case-control study using automated general practice data

  • Pharmacoepidemiology And Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objectives: To determine the risk of coughing as an adverse reaction to ACE inhibitors under everyday circumstances in a large population, and to study whether this adverse effect was duration or dose dependent.

Design: A population-based case-control study.

Setting: Ten general practices of 14 Dutch general practitioners (GP), in which all consultations, morbidity and medical interventions, including drugs prescribed, were registered over the 18 month period from 1st September, 1992 to 1st March, 1994.

Subjects: 1458 patients with incident coughing and up to four controls per case were obtained (total 4182 controls), matched for GP. All cases and controls were 20 years or older and had no record of respiratory infection, influenza, tuberculosis, asthma, chronic bronchitis, emphysema, congestive heart failure, sinusitis, laryngitis, haemoptysis or respiratory neoplasms during the study period.

Results: Cases were 2.1-times more likely than controls to have been exposed to ACE inhibitors (95% CI 1.5–3.1), but after adjustment the odds ratio was 1.4 (95% CI 0.9–2.1). The crude odds ratio for captopril was 1.3 (95% CI 0.7–2.5), for enalapril 2.6 (95% CI 1.6–4.2) and for lisinopril 2.0 (95% CI 0.5–9.3). The adjusted odds ratio for captopril was 0.9 (95% CI 0.4–1.7), for enalapril 1.7 (95% CI 1.03–2.8) and for lisinopril 1.7 (95% CI 0.4–7.9). For patients who had been on ACE inhibitor treatment for no longer than 2 months the odds ratio was 4.8 (95% CI 1.7–13.3). The odds ratio declined to 2.0 (95% CI 1.1–3.8) for those who had taken an ACE inhibitor for 2–6 months, and to 1.6 (95% CI 0.9–2.7) for those on ACE-inhibitors for more than 6 months.

Conclusion: The risk of coughing was increased twofold among ACE inhibitor users, but the odds ratios were no longer significant after controlling for several confounding factors. The risk of developing cough due to ACE-inhibitors declines with the duration of treatment, possibly due to depletion of susceptible persons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Havelka J, Vetter H, Studer A, Greminger P, Luscher T, Wollnik S, Siegenthaler W, Vetter W (1982) Acute and chronic effects of Angiotensin-Converting Enzyme Inhibitor Captopril in Severe Hypertension. Am J Cardiol 49:1467–1474

    Google Scholar 

  2. Sesoko S, Kaneko Y (1985) Cough associated with the use of captopril. Arch Intern Med 145:1524

    Google Scholar 

  3. Israili ZH, Hall WD (1992) Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med 117:234–242

    CAS  PubMed  Google Scholar 

  4. Inman WHW (1986) Enalapril-induced cough Lancet 2:1218

    Google Scholar 

  5. Coulter DM, Edwards IR (1987) Cough associated with captopril and enalapril. BMJ 294:1521–1523

    Google Scholar 

  6. Yeo WW, Ramsey LE (1990) Persistent dry cough with enalapril: incidence depends on method used. J Hum Hypertens 4:517–520

    Google Scholar 

  7. Stoller JK, Elghazawi A, Mehta AC, Vidt DG (1988) Captopril-induced cough. Chest 93:659–661

    Google Scholar 

  8. Webb D, Benjamin N, Collier J, Robinson B (1986) Enalapril-induced cough. Lancet 2:1094

    Google Scholar 

  9. Kaufman J, Casanova JE, Riendl P, Schlueter DP (1989) Bronchial hyperreactivity and cough due to angiotensin-converting enzyme inhibitors. Chest 95:544–548

    Google Scholar 

  10. Hume AL, Murphy JL, Lauerman SE (1989) Angiotensin-converting enzyme inhibitor-induced cough. Pharmacotherapy 9:88–90

    Google Scholar 

  11. Morice AH, Brown MJ, Higenbottam T (1989) Cough Associated with Angiotensin Converting Enzyme Inhibition. J Cardiovasc Pharmacol 13 [Suppl 3]:S59-S62

    Google Scholar 

  12. McEwan JR, Choudry N, Street R, Fuller RW (1989) Change in cough reflex after treatment with enalapril and ramipril. BMJ 299:13–16

    Google Scholar 

  13. Yeo WW, Foster G, Ramsay LE (1991) Prevalence of persistent cough during long-term enalapril treatment: controlled study versus nifedipine. Q J Med 80: 763–770

    Google Scholar 

  14. Poole MD, Postma DS (1991) Characterization of cough associated with angiotensin converting enzyme inhibitors. Otolaryngol Head Neck Surg 105:714–716

    Google Scholar 

  15. Yeo WW, Maclean D, Richardson PJ, Ramsey LE (1991) Cough and enalapril: assessment by spontaneous reporting and visual analogue scale under double-blind conditions. Br J Clin Pharmacol 31:356–359

    Google Scholar 

  16. Os I, Bratland B, Dahlof B, Gisholt K, Syvertsen JO, Tretli S (1992) Female sex as an important determinant of lisinopril-induced cough. Lancet 339:372

    Google Scholar 

  17. Strocchi E, Valtancoli, G, Ambrosioni E (1989) The incidence of cough during treatment with angiotensin converting enzyme inhibitors. J Hypertens 7 [Suppl 6]:S308-S309

    Google Scholar 

  18. Moore N, Noblet C, Joannides R, Ollagnier M, Imbs JL, Lagier G (1993) Cough and ACE inhibitors. Lancet 341:61

    Google Scholar 

  19. Lefebvre J, Poirier L, Lacourciere Y (1992) Prospective trial on captropril-related cough. Ann Pharmacother 26:161–164

    Google Scholar 

  20. Carre A, Vasmant D, Elmalem J, Thiery P (1991) Tolerability of ramipril in a multicenter study of mild-to-moderate hypertension in general practice. J Cardiovasc Pharmacol 18 [suppl 2]:S141-S143

    Google Scholar 

  21. Strocchi E, Valtancoli G, Ricci C, Malini PL, Bassein L, Ambrosioni E (1992) Postmarketing studies of subjective side effects; a case for strict methodological criteria and careful analysis of data. Pharmacol Res 25 [Suppl 1]:79–80

    Google Scholar 

  22. Visser LE, Stricker BHCh, Van der Velden J, Paes AHP, Bakker A (1995) ACE-inhibitor associated cough: a population-based case-control study. J Clin Epidemiol 48:851–857

    Google Scholar 

  23. Inman WHW, Rawson NSB, Wilton LV, Pearce GL, Speirs CJ (1988) Postmarketing Surveillance of enalapril. 1: Results of Prescription Event-Monitoring. BMJ 297:286–289

    Google Scholar 

  24. Cooper WD, Sheldon D, Brown D, Kimber GR, Isitt VL, Currie WJ (1987) Post-marketing surveillance of enalapril: experience in 11,710 hypertensive patients in general practice. J R Coll Gen Pract 37:346–349

    Google Scholar 

  25. Van der Lei J, Duisterhout JS, Westerhof HP, Van der Does E Cromme PVM, Boon WM, Van Bemmel JH (1993) The introduction of computer-based patient records in the Netherlands. Ann Int Med 119:1036–1041

    Google Scholar 

  26. Lamberts H, Woods M (1987) International classification of primary care. Oxford University Press, Oxford

    Google Scholar 

  27. Anonymous. (1987) Anatomical therapeutic chemical (ATC) index: Including defined daily doses (DDD) for plain substances. World Health Organization. Oslo

  28. Puolijoki HJ, Nieminen MM, Siitonen LO, Lahdensuo AH, Reinikainen PM (1989) Is a simultaneous beta-blocker therapy a risk factor for enalapril-induced cough? Respiration 55:127–128

    Google Scholar 

  29. Kamei J, Kasuya Y (1992) The effect of hydrochlorothiazide on the enhanced coughing associated with treatment with enalapril. Eur J Pharmacol 213:137–139

    Google Scholar 

  30. Fogari R, Zoppi A, Tettamanti F, Malamani GD, Tinelli C, Salvetti A (1992) Effects of nifedipine and indomethacin on cough induced by angtiotensin converting enzyme inhibitors: a double-blind radomized, cross-over study, J Cardiovasc Pharmacol 19:670–673

    Google Scholar 

  31. Kleinbaum DG, Kupper LL, Muller KE (1988) Applied regression analysis and other multivariate methods. PWS-Kent Publishing Company, Boston

    Google Scholar 

  32. Egret. ⊠ Statistics and Epidemiology Research Corporation, Seattle, WA.

  33. Just PM (1989) The positive association of cough with angiotensin-converting enzyme inhibitors. Pharmacotherapy 9:82–87

    Google Scholar 

  34. Sebastian JL, Mc Kinney WP, Kaufman J, Young MJ (1991) Angiotensin converting enzyme inhibitors and cough. Chest 99:36–39

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Erasmus University Medical School, room Ee 2126 Dr. Molewaterplein 50, NL-3015 GE, Rotterdam, The Netherlands

    L. E. Visser & B. H. Ch. Stricker

  2. Department of Medical Informatics, Erasmus University, Rotterdam, The Netherlands

    A. E. Vlug & J. van der Lei

Authors
  1. L. E. Visser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. H. Ch. Stricker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. E. Vlug
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. van der Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Visser, L.E., Stricker, B.H.C., Vlug, A.E. et al. Cough due to ace inhibitors: a case-control study using automated general practice data. Eur J Clin Pharmacol 49, 439–444 (1996). https://doi.org/10.1007/BF00195928

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00195928

Key words

Search

Navigation