Skip to main content

Development and validation of a Clinical prediction rule for angiotensin-converting enzyme inhibitor-induced cough

Journal of General Internal Medicine volume 19, pages 684–691 (2004)Cite this article

Abstract

BACKGROUND: Angiotensin-converting enzyme inhibitors are effective for many cardiovascular diseases and are widely prescribed, but cough sometimes necessitates their withdrawal.

OBJECTIVE: To develop and validate a model that predicts, by using information available at first prescription, whether a patient will develop cough within 6 months.

DESIGN: Retrospective cohort study with derivation and validation sets.

SETTING: Outpatient clinics affiliated with an urban tertiary care hospital.

PATIENTS: Clinical data were collected from electronic charts. The derivation set included 1,125 patients and the validation set included 567 patients.

INTERVENTIONS: None.

MEASUREMENTS: Angiotensin-converting enzyme inhibitor-induced cough assessed by predetermined criteria.

RESULTS: In the total cohort, 12% of patients developed angiotensin-converting enzyme inhibitor-induced cough. Independent multivariate predictors of cough were older age, female gender, non-African American (with East Asian having highest risk), no history of previous angiotensin-converting enzyme inhibitor use, and history of cough due to another angiotensin-converting enzyme inhibitor. Patients with a history of angiotensin-converting enzyme inhibitor-induced cough were 29 times more likely to develop a cough than those without this history. These factors were used to develop a model stratifying patients into 4 risk groups. In the derivation set, low-risk, average-risk, intermediate-risk, and high-risk groups had a 6%, 9%, 22%, and 55% probability of cough, respectively. In the validation set, 4%, 14%, 20%, and 60% of patients in these 4 groups developed cough, respectively.

CONCLUSIONS: This model may help clinicians predict the likelihood of a particular patient developing cough from an angiotensin-converting enzyme inhibitor at the time of prescribing, and may also assist with subsequent clinical decisions.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

References

  1. Khalil ME, Basher AW, Brown EJ Jr., Alhaddad IA. A remarkable medical story: benefits of angiotensin-converting enzyme inhibitors in cardiac patients. J Am Coll Cardiol. 2001;37:1757–64.

    PubMed  Article  CAS  Google Scholar 

  2. Halkin A, Keren G. Potential indications for angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease. Am J Med. 2002;112:126–34.

    PubMed  Article  CAS  Google Scholar 

  3. Cherry DK, Woodwell DA. National Ambulatory Medical Care Survey: 2000 Summary. Advance Data from Vital and Health Statistics; No. 328. Hyattsville, Md: National Center for Health Statistics; 2002.

    Google Scholar 

  4. Sebastian JL, McKinney WP, Kaufman J, Young MJ. Angiotensin-converting enzyme inhibitors and cough. Prevalence in an outpatient medical clinic population. Chest. 1991;99:36–9.

    PubMed  CAS  Google Scholar 

  5. Simon SR, Black HR, Moser M, Berland WE. Cough and ACE inhibitors. Arch Intern Med. 1992;152:1698–700.

    PubMed  Article  CAS  Google Scholar 

  6. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med. 1992;117:234–42.

    PubMed  CAS  Google Scholar 

  7. Smyrnios NA, Irwin RS, Curley FJ, French CL. From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults. Arch Intern Med. 1998;158:1222–8.

    PubMed  Article  CAS  Google Scholar 

  8. Gandhi TK, Burstin HR, Cook EF, et al. Drug complications in outpatients. J Gen Intern Med. 2000;15:149–54.

    PubMed  Article  CAS  Google Scholar 

  9. Grossman E, Messerli FH, Neutel JM. Angiotensin II receptor blockers: equal or preferred substitutes for ACE inhibitors? Arch Intern Med. 2000;160:1905–11.

    PubMed  Article  CAS  Google Scholar 

  10. Speirs C, Wagniart F, Poggi L. Perindopril postmarketing surveillance: a 12 month study in 47,351 hypertensive patients. Br J Clin Pharmacol. 1998;46:63–70.

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  12. Os I, Bratland B, Dahlof B, Gisholt K, Syvertseri JO, Tretli S. Female preponderance for lisinopril-induced cough in hypertension. Am J Hypertens. 1994;7:1012–5.

    PubMed  CAS  Google Scholar 

  13. Elliott WJ. Higher incidence of discontinuation of angiotensin converting enzyme inhibitors due to cough in black subjects. Clin Pharmacol Ther. 1996;60:582–8.

    PubMed  Article  CAS  Google Scholar 

  14. Kostis JB, Shelton B, Gosselin G, et al. Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). SOLVD Investigators. Am Heart J. 1996;131:350–5.

    PubMed  Article  CAS  Google Scholar 

  15. Woo KS, Norris RM, Nicholls G. Racial difference in incidence of cough with angiotensin-converting enzyme inhibitors (a tale of two cities). Am J Cardiol. 1995;75:967–8.

    PubMed  Article  CAS  Google Scholar 

  16. Ishimitsu T, Yagi S, Ebihara A, et al. Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension. Jpn Heart J. 1997;38:831–40.

    PubMed  CAS  Google Scholar 

  17. Ajayi AA, Adigun AQ. Angioedema and cough in Nigerian patients receiving ACE inhibitors. Br J Clin Pharmacol. 2000;50:81–2.

    PubMed  Article  CAS  Google Scholar 

  18. Malini PL, Strocchi E, Fiumi N, Ambrosioni E, Ciavarella A. ACE inhibitor-induced cough in hypertensive type 2 diabetic patients. Diabetes Care. 1999;22:1586–7.

    PubMed  Article  CAS  Google Scholar 

  19. Lee YJ, Chiang YF, Tsai JC. Severe nonproductive cough and cough-induced stress urinary incontinence in diabetic postmenopausal women treated with ACE inhibitor. Diabetes Care. 2000;23:427–8.

    PubMed  Article  CAS  Google Scholar 

  20. Keane WF, Polis A, Wolf D, Faison E, Shahinfar S. The long-term tolerability of enalapril in hypertensive patients with renal impairment. Nephrol Dial Transplant. 1997;12(suppl 2):75–81.

    PubMed  Google Scholar 

  21. Gilchrist NL, Richards AM, March R, Nicholls MG. Effect of sulindac on angiotensin converting enzyme inhibitor-induced cough: randomised placebo-controlled double-blind cross-over study. J Hum Hypertens. 1989;3:451–5.

    PubMed  CAS  Google Scholar 

  22. Fogari R, Zoppi A, Tettamanti F, Malamani GD, Tinelli C, Salvetti A. Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study. J Cardiovasc Pharmacol. 1992;19:670–3.

    PubMed  Article  CAS  Google Scholar 

  23. Tenenbaum A, Grossman E, Shemesh J, Fisman EZ, Nosrati I, Motro M. Intermediate but not low doses of aspirin can suppress angiotensin-converting enzyme inhibitor-induced cough. Am J Hypertens. 2000;13:776–82.

    PubMed  Article  CAS  Google Scholar 

  24. Knox AJ, Pang L. Tackling ACE inhibitor cough. Lancet. 1997;350:814.

    PubMed  Article  CAS  Google Scholar 

  25. Tu JV, Naylor CD. Clinical prediction rules. J Clin Epidemiol. 1997;50:743–4.

    PubMed  Article  CAS  Google Scholar 

  26. Metz CE. Basic principles of ROC analysis. Semin Nucl Med. 1978;8:283–98.

    PubMed  CAS  Google Scholar 

  27. Laupacis A, Sekar N, Stiell IG. Clinical prediction rules. A review and suggested modifications of methodological standards. JAMA. 1997;277:488–94.

    PubMed  Article  CAS  Google Scholar 

  28. Bates DW, Lee TH. Rapid classification of positive blood cultures. Prospective validation of a multivariate algorithm. JAMA. 1992;267:1962–6.

    PubMed  Article  CAS  Google Scholar 

  29. Bates DW, Leape LL, Cullen DJ, et al. Effect of computerized physician order entry and a team intervention on prevention of serious medication errors. JAMA. 1998;280:1311–6.

    PubMed  Article  CAS  Google Scholar 

  30. Raschke RA, Gollihare B, Wunderlich TA, et al. A computer alert system to prevent injury from adverse drug events: development and evaluation in a community teaching hospital. JAMA. 1998;280:1317–20.

    PubMed  Article  CAS  Google Scholar 

  31. Wang SJ, Kuperman GJ, Ohno-Machado L, Onderdonk A, Sandige H, Bates DW. Using electronic data to predict the probability of true bacteremia from positive blood cultures. Proc AMIA Symp. 2000:893–7.

  32. Goldman L, Cook EF, Brand DA, et al. A computer protocol to predict myocardial infarction in emergency department patients with chest pain. N Engl J Med. 1988;318:797–803.

    PubMed  CAS  Article  Google Scholar 

  33. Goldman L, Cook EF, Johnson PA, Brand DA, Rouan GW, Lee TH. Prediction of the need for intensive care in patients who come to the emergency departments with acute chest pain. N Engl J Med. 1996;334:1498–504.

    PubMed  Article  CAS  Google Scholar 

  34. Bates DW, Ebell M, Gotlieb E, Zapp J, Mullins HC. A proposal for electronic medical records in U.S. primary care. J Am Med Inform Assoc. 2003;10:1–10.

    PubMed  Article  Google Scholar 

  35. Randolph AG, Guyatt GH, Calvin JE, Doig G, Richardson WS. Understanding articles describing clinical prediction tools. Evidence Based Medicine in Critical Care Group. Crit Care Med. 1998;26:1603–12.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital, 75 Francis Street, 02115, Boston, MA

    Takeshi Morimoto MD, MPH, Tejal K. Gandhi MD, MPH, Julie M. Fiskio BS, Andrew C. Seger RPh, Joseph W. So BS, E. Francis Cook ScD &  David W. Bates MD, MSc

  2. Harvard School of Public Health, Boston, Mass

    Takeshi Morimoto MD, MPH, E. Francis Cook ScD &  David W. Bates MD, MSc

  3. Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Takeshi Morimoto MD, MPH & Tsuguya Fukui MD, MPH

  4. Harvard Medical School, Boston, Mass

    Tejal K. Gandhi MD, MPH &  David W. Bates MD, MSc

Authors
  1. Takeshi Morimoto MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tejal K. Gandhi MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julie M. Fiskio BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew C. Seger RPh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joseph W. So BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Francis Cook ScD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tsuguya Fukui MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David W. Bates MD, MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David W. Bates MD, MSc.

Additional information

This work was supported in part by grants from the Pfizer Health Research Foundation and the Health Care Science Institute and grant R01-HS11169 from the Agency for Healthcare Research and Quality.

Dr. Morimoto received fellowship grant support from the St. Luke’s Life Science Institute, Tokyo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Morimoto, T., Gandhi, T.K., Fiskio, J.M. et al. Development and validation of a Clinical prediction rule for angiotensin-converting enzyme inhibitor-induced cough. J GEN INTERN MED 19, 684–691 (2004). https://doi.org/10.1111/j.1525-1497.2004.30016.x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1111/j.1525-1497.2004.30016.x

Key words

  • adverse drug events
  • angiotensin-converting enzyme inhibitors
  • cough
  • clinical prediction rule