An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors

J Eval Clin Pract. 2004 Nov;10(4):499-509. doi: 10.1111/j.1365-2753.2003.00484.x.


Rationale, aims and objectives: To identify potential factors leading to discontinuation of angiotensin-converting enzyme (ACE) inhibitors because of adverse drug events.

Methods: Retrospective cohort study was conducted at outpatient clinics affiliated with an urban tertiary care hospital. ACE inhibitors were administered to 2225 consecutive outpatients.

Results: In 19% of the total cohort, ACE inhibitors were discontinued because of adverse drug events. Cox proportional hazard model identified the following independent risk factors for discontinuation because of adverse drug events: age, female gender, ethnicity other than African American or Latino, no history of previous ACE inhibitor use, history of cough caused by another ACE inhibitor, hypertension, anxiety or depression, no hemodialysis, and elevated creatinine. History of smoking was shown to be a risk factor for cough [hazard ratio (HR): 2.5; 95% confidence interval (CI): 1.1-5.7], angioedema (HR: 2.7; 95% CI: 1.1-7.0), and hyperkalaemia (HR: 5.4; 95% CI: 1.3-23.2). History of ACE inhibitor-induced cough was not only a risk factor for cough (HR: 12.9; 95% CI: 7.5-22.3) but also for angioedema (HR: 9.1; 95% CI: 2.1-39.9). Patients with creatinine > or = 1.6 mg dL(-1) were likely to discontinue ACE inhibitors because of renal dysfunction (HR: 4.7; 95% CI: 1.5-12.7) and hyperkalaemia (HR: 10.9; 95% CI: 3.1-39.0). East Asians were more likely to develop cough (HR: 2.5; 95% CI: 1.1-5.7) and hyperkalaemia (HR: 80.3; 95% CI: 5.4-1190) and African Americans to develop angioedema (HR: 3.5; 95% CI: 1.3-8.9).

Conclusions: Although further validation is necessary, these risk factors should help doctors identify patients with elevated risk for adverse drug events because of ACE inhibitors.

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*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Boston
  • Cohort Studies
  • Cough / chemically induced
  • Female
  • Hospitals, Urban
  • Humans
  • Male
  • Middle Aged
  • Outpatient Clinics, Hospital
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors


  • Angiotensin-Converting Enzyme Inhibitors