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PHARMACOEPIDEMIOLOGY

Association Between ACE Inhibitors and Acute Pancreatitis in the Elderly

Staff Pharmacist, Princess Margaret Hospital, Toronto, Ontario, Canada

Muhammad Mamdani, PharmD MA MPH

Scientist, Institute for Clinical Evaluative Sciences, Toronto; Assistant Professor, Faculty of Pharmacy, University of Toronto, Toronto

Cynthia A Jackevicius, BScPharm MSc FCSHP

Pharmacy Practice Leader, Associate — Women's Health Program, University Health Network; Assistant Professor, Faculty of Medicine and Faculty of Pharmacy, University of Toronto; Adjunct Scientist, Institute for Clinical Evaluative Sciences, Toronto

Karen Tu, MD MSc

Associate Scientist, Institute for Clinical Evaluative Sciences; Assistant Professor, Faculty of Medicine, University of Toronto; Staff Physician, University Health Network — Toron- to Western Hospital

Reprints: Muhammad Mamdani PharmD MA MPH, Institute for Clinical Evaluative Sciences, 2075 Bayview Ave. — G215, Toronto, Ontario M4N 3M5, Canada, FAX 416/480-6048, E-mail muhammad.mamdani{at}ices.on.ca

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor–induced acute pancreatitis has been described in various case reports and drug surveillance databases. At present, no epidemiologic studies examining the potential association between ACE inhibitors and acute pancreatitis have been identified.

OBJECTIVE: To determine whether there is an association between ACE inhibitor use and pancreatic events (acute pancreatitis, pancreatic surgery).

METHODS: A retrospective cohort of Ontario residents aged 66 years was created using population-based administrative databases from January 1, 1994, through March 31, 2000. We compared the incidence of pancreatic events among new users of ACE inhibitors (study group), warfarin (null baseline group), and dihydropyridine calcium-channel antagonists (DCCAs; disease control group) using multivariate Cox proportional hazard models.

OUTCOME MEASURES: The primary outcome measure was hospitalization with acute pancreatitis; the secondary outcome measure was incidence of pancreatic surgery.

RESULTS: For acute pancreatitis, the crude incidence rates per 10 000 person-years were 9.0 for the ACE inhibitor group (n = 174 824); 7.1 for the DCCA group (n = 73 719), and 7.6 for the warfarin group (n = 40 057). Relative to warfarin users, neither ACE inhibitor users (adjusted rate ratio [aRR] = 1.35; 95% CI 0.94 to 1.93) nor DCCA users (aRR = 1.09; 95% CI 0.72 to 1.62) were at significantly higher risk of hospitalization for acute pancreatitis. For pancreatic surgery in the same population, the crude incidence rates per 10 000 person-years were 10.5 for the ACE inhibitor group, 10.6 for the DCCA group, and 10.7 for the warfarin group. Relative to subjects taking warfarin, neither ACE inhibitor users (aRR = 1.09; 95% CI 0.80 to 4.49) nor DCCA users (aRR = 1.11; 95% CI 0.79 to 1.56) were at significantly higher risk for pancreatic surgery.

CONCLUSIONS: The use of ACE inhibitors does not appear to be associated with significant risk of acute pancreatitis among the elderly.

Key Words: acute pancreatitis, angiotensin-converting enzyme inhibitors, elderly, pharmacoepidemiology

Published Online, June 10, 2003. www.theannals.com, DOI 10.1345/aph.1C270