Published Online
on April 14, 2008

A more recent version of this article appeared on June 1, 2008

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Submitted on January 13, 2008
Revised on January 28, 2008

Angioedema Incidence in US Veterans Initiating Angiotensin-Converting Enzyme Inhibitors

Donald R. Miller^*; Susan A. Oliveria; Dan R. Berlowitz; Benjamin G. Fincke; Paul Stang; and David E. Lillienfeld

From the Center for Health Quality, Outcomes, and Economic Research (D.R.M., D.R.B., B.G.F.), Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Mass; the Department of Health Policy and Management (D.R.M., D.R.B., B.G.F.), Boston University School of Public Health, Mass; EpiSource LLC (S.A.O.), New York; the Department of Public Health (S.A.O.), Weill Medical College of Cornell University, New York; the Department of Medicine (S.A.O.), Memorial Sloan-Kettering Cancer Center, New York; Johnson & Johnson Pharmaceutical Research and Development (P.S.), Titusville, NJ; and Health Research and Policy (D.E.L.), Stanford University, Palo Alto, Calif.

^* To whom correspondence should be addressed. E-mail: drmiller{at}bu.edu.

Abstract—Angioedema is a rare but potentially serious complication of angiotensin-converting enzyme inhibitor (ACE) use. We conducted a study to estimate incidence of ACE-related angioedema and explore its determinants in a large racially diverse patient population. We used linked medical and pharmacy records to identify all patients in the US Veterans Affairs Health Care System from April 1999 through December 2000 who received first prescriptions for antihypertensive medications. We studied 195 192 ACE initiators and 399 889 patients initiating other antihypertensive medications (OAH). New angioedema was identified by diagnosis codes using methods validated in a national sample of 869 angioedema cases with confirmation for over 95% of cases. Overall, 0.20% of ACE initiators developed angioedema while on the medication and the incidence rate was 1.97 (1.77 to 2.18) cases per 1000 person years. This compares with a rate of 0.51 (0.43 to 0.59) in OAH initiators and the adjusted relative risk estimate was 3.56 (2.82 to 4.44). Fifty five percent of cases occurred within 90 days of first ACE use but risk remained elevated with prolonged use, even beyond 1 year. We estimate that 58.3% of angioedema in patients starting antihypertensives was related to ACE. We also found that angioedema rates were nearly 4-fold higher in blacks, 50% higher in women, and 12% lower in those with diabetes. This study provides a reliable estimate of angioedema incidence associated with ACE use in a diverse nontrial patient population, confirming that the incidence is low, but finding substantial variation by race, sex, and diabetes status.

Key words: angioedema • angiotensin-converting enzyme inhibitors • antihypertensive agents • adverse effects • pharmacoepidemiology • drug toxicity

Related Article:

Angiotensin-Converting Enzyme Inhibitors and Angioedema: Estimating the Risk

Michael A. Weber and Franz H. Messerli
Hypertension 2008 51: 1465-1467. [Full Text] [PDF]

This article has been cited by other articles:

				M. A. Weber and F. H. Messerli Angiotensin-Converting Enzyme Inhibitors and Angioedema: Estimating the Risk Hypertension, June 1, 2008; 51(6): 1465 - 1467. [Full Text] [PDF]