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

J Gen Intern Med. 2004 Jun;19(6):684-91. doi: 10.1111/j.1525-1497.2004.30016.x.


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 1125 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Cardiovascular Diseases / drug therapy*
  • Cohort Studies
  • Cough / chemically induced
  • Cough / etiology*
  • Decision Making
  • Female
  • Forecasting*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Reproducibility of Results
  • Risk Factors
  • Time Factors


  • Angiotensin-Converting Enzyme Inhibitors