Journal of General Internal Medicine

, Volume 19, Issue 6, pp 684–691

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

  • Takeshi Morimoto
  • Tejal K. Gandhi
  • Julie M. Fiskio
  • Andrew C. Seger
  • Joseph W. So
  • E. Francis Cook
  • Tsuguya Fukui
  • David W. Bates
Original Articles


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.


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.

Key words

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


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Copyright information

© Society of General Internal Medicine 2004

Authors and Affiliations

  • Takeshi Morimoto
    • 1
    • 2
    • 3
  • Tejal K. Gandhi
    • 1
    • 4
  • Julie M. Fiskio
    • 1
  • Andrew C. Seger
    • 1
  • Joseph W. So
    • 1
  • E. Francis Cook
    • 1
    • 2
  • Tsuguya Fukui
    • 3
  • David W. Bates
    • 1
    • 2
    • 4
  1. 1.Division of General Internal Medicine and Primary CareBrigham and Women’s HospitalBoston
  2. 2.Harvard School of Public HealthBoston
  3. 3.Department of Clinical EpidemiologyKyoto University Graduate School of MedicineKyotoJapan
  4. 4.Harvard Medical SchoolBoston

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