title: The differential effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers with respect to foot ulcer and limb amputation in those with diabetes.
abstract: Diabetic foot ulcers (DFU) or lower extremity amputation (LEA) are complications of diabetes. In those with diabetes, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are commonly used to prevent the progression of kidney disease. Recent studies have indicated that angiotensin may affect angiogenesis and wound repair. Our goal was to evaluate in those with diabetes the likelihood of developing a DFU or LEA among users of ACEi or ARB using a retrospective cohort design of general practices in the United Kingdom. We studied 40,342 individuals at least 35 years of age with diabetes who were first prescribed ACEi or ARB between 1995 and 2006. A total of 35,153 individuals were treated with ACEi, 12,437 individuals with ARB, and 7,310 both. The hazard ratio for DFU was 0.50 (95% confidence intervals: 0.43, 0.59), showing an increased risk of DFU for those using ACEi vs. ARB. The hazard ratio for LEA was 0.72 (0.48, 1.01). However, among those with lower extremity peripheral arterial disease the hazard ratio was 0.45 (0.22, 0.91) for the new onset of a LEA. In conclusion, among those with diabetes, exposure to ACEi as compared with ARB increases the risk of developing a DFU or LEA.
authors.affiliation: Department of Dermatology and Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. margo@mail.med.upenn.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Margolis
authors.forename: Ole
authors.initials: O
authors.lastname: Hoffstad
authors.forename: Stephen
authors.initials: S
authors.lastname: Thom
authors.forename: Warren
authors.initials: W
authors.lastname: Bilker
authors.forename: Arturo R
authors.initials: AR
authors.lastname: Maldonado
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cohen
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Timothy
authors.initials: T
authors.lastname: Crombleholme
mesh_terms: D000328:Adult; D000368:Aged; D000671:Amputation, Surgical / Q000639:trends*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D004739:England; D005260:Female; D005500:Follow-Up Studies; D016523:Foot Ulcer / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007866:Leg / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014852:Wales
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors