Severe intestinal malabsorption associated with ACE inhibitor or angiotensin receptor blocker treatment. An observational cohort study in Germany and Italy.

PURPOSE: The angiotensin II receptor blocker (ARB) olmesartan has been recently associated with sprue-like enteropathy (SLE), a gastrointestinal condition characterized by intestinal malabsorption (IM) and severe diarrhea. Whether the increased risk of SLE is substance-specific or a class effect involving all ARBs is uncertain. The aim of this study is to assess the risk of enteropathy associated with ARBs and angiotensin converting enzyme inhibitors (ACE-i) by using data from large administrative and claim databases.

METHODS: We obtained data from Italian local health-care units and a large German claim database and included patients treated with olmesartan, other ARBs, and ACE-i. In the absence of a specific diagnosis code for SLE, International Classification of Diseases codes for IM were used. Analysis implemented a Poisson regression with robust error variance procedure, which allowed accounting for different clusters (local health-care units and countries) and correctly estimating the standard error for the relative risk of rare event occurrence.

RESULTS: Patients were divided into 3 groups: olmesartan (25.591, 5.5%), other ARBs (104.901, 22.5%), and ACE-i patients (334.951, 72.0%). Baseline characteristics were similar overall. The incidence of unspecified IM in ACE-i patients was not different compared with that of olmesartan, whereas a higher rate ratio was observed when comparing ARB patients with the olmesartan group (RR: 2.50, 95% CI 1.21 to 5.19, P .01). When International Classification of Diseases codes for coeliac disease were included, no differences were observed.

CONCLUSIONS: We could not confirm previous findings of a higher risk of malabsorption in olmesartan-only patients, and drug-induced enteropathy should be considered the result of exposure to the class of ARBs rather than a specific drug-related effect.