Blockers of Angiotensin Other Than Olmesartan in Patients With Villous Atrophy: A Nationwide Case-Control Study

Abstract

Objective To examine the association between previous use of non-olmesartan angiotensin receptor blockers (ARBs) or any angiotensin-converting enzyme inhibitors (ACEIs) in patients with small-intestinal villous atrophy (VA) as compared with general population matched controls. Patients and methods A case-control study was used to link nationwide histopathology data on 2933 individuals with VA (Marsh grade 3) to the Swedish Prescribed Drug Register to examine the association between use of ACEIs as well as the specific use of ARBs other than olmesartan and subsequent VA. Olmesartan is not available in Sweden and so this exposure was not examined. All individuals with VA were biopsied between July 1st 2005 and January 29th 2008 and matched on age, sex, calendar period of birth and county of residence to 14,571 controls from the general population. Results Use of non-olmesartan ARBs was not associated with VA (Odds ratio (OR) = 0.84; 95 % confidence interval [CI] = 0.64-1.09; P=.19). Neither was VA associated with a prior medication of any ACEIs (OR = 1.08; 95% CI = 0.90-1.30; P=.41). Restricting the analysis to individuals with repeated prescriptions for ACEIs or ARBs revealed only marginally changed risk estimates for VA. Conclusion The lack of association between use of ACEIs and non-olmesartan ARBs and subsequent VA suggests that, in the general population, these medications are not a major risk factor for VA development.

Factors associated with villus atrophy in symptomatic coeliac disease patients on a gluten‐free diet

“…Olmesartan can cause a severe sprue‐like enteropathy that mimics coeliac disease histologically, and which improves following medication cessation . There are case reports of similar occurrences with other members of the angiotensin receptor antagonist class; however, this has not been demonstrated in larger studies . In our study, angiotensin receptor antagonist use was not associated with impaired mucosal healing in this study; however, the overall prevalence of use was too low to detect an effect size of a similar magnitude to that seen for NSAIDs and PPIs.…”

“…The relevance of other types of symptoms on risk of persistent villus atrophy has not, however, been studied. Drug‐induced enteropathy is well recognised and has been linked to use of angiotensin‐receptor blockers, non‐steroidal anti‐inflammatory drugs (NSAIDs), and possibly proton‐pump inhibitors (PPIs), however the impact of use of these medications on healing of villus atrophy in coeliac disease is not known …”

Olmesartan‐associated duodenal villous atrophy, an emerging clinical issue

“…A third study did not find an increased risk of intestinal malabsorption with olmesartan compared with other ARBcor ACE inhibitors in admitted patients in Germany and Italy, however it did not assess risk as a function of duration of therapy, there were limited number of events and 95% confidence intervals between groups were wide and overlapping. There is further support from Sweden, where olmesartan is not available, that this is a particular risk with olmesartan, rather than a class effect of ARB. A case–control study of 2933 histologically confirmed cases of villous atrophy, did not find an association between use of ACE inhibitors or non‐olmesartan ARB, suggesting that these medications are not a major risk factor for the development of villous atrophy in the general population.…”

Olmesartan - associated sprue-like enteropathy and colagenous colitis: A case report and review of literature

“…Olmesartan-induced selective AT1 receptor blockade also results in a translocation of AT2 receptors to the outer part of the basolateral cell membrane. [14,15] This receptor translocation favors the binding of angiotensin II to AT2 receptors, possibly resulting in the pro-apoptotic effect seen in OAE. The duodenal-jejunal histology is characterized by villous atrophy and increased intra-epithelial lymphocytes (CD3 and CD8 lymphocytes) apparently due to apoptosis of enterocytes.…”

“…Recent reports have suggested an association between use of olmesartan and a sprue-like enteropathy, with affected patients presenting with severe, protracted diarrhea and weight loss that improves after discontinuation of olmesartan. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Although the symptoms and histologic findings of olmesartan-associated enteropathy (OAE) resemble severe celiac disease, negative laboratory testing for celiac disease and lack of a response to a gluten-free diet suggest that OAE is a separate clinical entity. The pathogenesis of this entity remains to be elucidated.…”