Su1776 Risk of Serious Upper Gastrointestinal (UGI) Complications in Patients Receiving Multiple Non-Selective NSAIDs for at Least 4 Weeks: A Series of Systematic Reviews and Meta-Analyses of Randomized Controlled Trials (RCT), Cohort and Case Control Studies

Abstract

Background:Treatment with non-selective nonsteroidal anti-inflammatory drugs (nsNSAIDs) is associated with increased risk of serious UGI complications, mainly peptic ulcer bleeding and perforation. Treatment with multiple nsNSAIDs is believed to further increase this risk. However, the precise estimate of the magnitude of this relative risk and our confidence for this estimate are unknown. Aim: By systematic reviews and meta-analyses of RCTs, cohort and case control studies, to estimate the risk of serious UGI complications with treatment with multiple nsNSAIDs for at least 4 weeks compared to treatment with a single nsNSAID. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE, CENTRAL, TOXILINE, and LILACS up to April2010. We included fully-published studies (RCTs, cohort or case control studies) that assessed the relative risk of confirmed serious UGI complications in adults who had received multiple nsNSAIDs for at least 4 weeks, compared to treatment with a single nsNSAID. No language restrictions were applied. Study selection and data extraction were conducted independently by two authors. StatsDirect® 2.7.7 was used to calculate pooled odds ratio (OR) with 95% confidence intervals (CI) with the MantelHaenszel and inverse variance method (random effects model). Heterogeneity among studies was assessed with the Cochrane Q test. Results:No RCT had randomized patients to multiple nsNSAIDs vs. single nsNSAID for more than 4 weeks. Only one cohort study provided data that allowed calculation of the OR for serious UGI complications for patients on multiple nsNSAIDs vs. patients on a single nsNSAID (OR 3.1, 95% CI 0.7 11.6). The adjusted OR for serious UGI complications for patients on multiple nsNSAIDs compared to those who did not use nsNSAIDs or aspirin was 5.82, 95% CI 2.08 16.3. No case control study provided data allowing the calculation of the risk for serious UGI complications for patients on multiple nsNSAIDs vs. those on a single nsNSAID. Three case control studies provided data that allowed calculation of the OR for serious UGI complications for patients on multiple nsNSAIDs vs. no use of any nsNSAID (OR 8.35, 95% CI 6.28 -11.11, no significant heterogeneity between studies, p 0.90). Conclusions: Limited evidence indicates that treatment with multiple nsNSAIDs for at least 4 weeks increases the risk of serious UGI complications approximately 3-fold compared to treatment with a single nsNSAID. The risk of serious UGI complications in patients using multiple nsNSAIDs is 6to 8-fold higher than in those who do not use any nsNSAID. These results confirm that patients on multiple nsNSAIDs are at high risk for serious UGI complications and, therefore, could benefit from gastroprotective strategies.