Comparative Effectiveness of Olmesartan and Other Angiotensin Receptor Blockers in Diabetes Mellitus

Abstract

Olmesartan has been linked with increased risk of cardiovascular mortality and sprue-like enteropathy. We compared outcomes between olmesartan and other angiotensin receptor blockers in a large clinical registry of patients with diabetes mellitus. A retrospective cohort analysis using nationwide US-integrated insurance and laboratory claims was performed in 45 185 incident diabetic angiotensin receptor blocker users, including 10 370 (23%) olmesartan users. Hazard ratios were computed using time-dependant Cox models adjusted for sociodemographic characteristics, comorbidities, laboratory data, drug use, healthcare utilization, and the propensity to receive olmesartan. Blood pressure data were unavailable. Subjects were followed up for 116 721 patient-years. The primary end point was all-cause hospitalization or all-cause mortality and occurred in 10 915 (24%) patients. Average age was 54.3±9.6 years, 52% were men, 17% had cardiovascular disease, and 10% chronic kidney disease. Compared with other angiotensin receptor blockers, the adjusted hazard for olmesartan was 0.99 (95% confidence interval, 0.94–1.05) for all-cause hospitalization and mortality; 0.90 (0.62–1.30) for all-cause mortality; 0.99 (0.94–1.05) for all-cause hospital admission; 0.88 (0.78–1.00) for cardiovascular disease–related admission, and 1.09 (0.98–1.20) for gastrointestinal disease–related hospitalization in the overall cohort. Olmesartan use was associated with an adjusted hazard for the primary outcome of 1.11 (0.99–1.24) in subjects with history of cardiovascular disease and 1.21 (1.04–1.41) in subjects with chronic kidney disease. In conclusion, there is no robust signal for harm with olmesartan use. Risk may be increased in kidney disease; thus, given the widespread availability of alternate agents, olmesartan should be used with caution in this subgroup pending further study.

Olmesartan-associated enteropathy: results of a national survey

“…Clinical, biological and histological manifestations All 32 patients (100%) had diarrhoea, with a median number of 8 liquid stools per day [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Twenty-four patients (75%) had abdominal pain, which was rarely severe (n = 3).…”

“…In addition, a recent epidemiological study performed in France has shown a significant association between hospitalisation for malabsorption and olmesartan prescription as compared with angiotensin-converting enzyme inhibitors and other sartans. 21 The lack of association between gastrointestinal events and olmesartan found in the ROADMAP trial 19 and in the paper by Padwal et al 20 could be due to the confounding effect of diabetic neuropathy, which may provoke chronic diarrhoea. In addition, the incidence of olmesartan enteropathy is low and may require large populations of patients to be clearly demonstrated.…”

“…18,19 More recently, a retrospective cohort analysis performed in 45 185 (116 721 patient-years) diabetic patients, compared olmesartan with other sartans and found no significant association between olmesartan and gastrointestinal disease-related hospitalisation. 20 Therefore, the association between enteropathy and olmesartan has been called into question. Following the report by Rubio Tapia et al, 15 we decided to perform a survey of enteropathy associated with olmesartan and other sartans in France.…”

“…The median cumulative hospital stay was 29 days . Four patients required intensive care (12 days [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]). Seven patients required enteral nutrition (30 days ) and 10 required parenteral nutrition (29 days ).…”

“…Three patients were hospitalised (12 days [12][13][14][15][16][17][18][19][20][21][22]), and two required intensive care. No patient received artificial nutrition, steroids or immunosuppressants.…”