Su1608 Comparison Between Oral and Intravenous Administration of Proton Pump Inhibitor Dosing With 24 Hours Intragastric pH: A Prospective, Randomized, Controlled Trial

Abstract

Background: Use of non-selective (ns) NSAIDs is associated with increased risk of serious UGI complications, mainly peptic ulcer bleeding and perforation. Concomitant use of clopidogrel 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: To estimate the risk of serious UGI complications with concomitant use of nsNSAIDs and clopidogrel for at least 4 weeks compared to use of nsNSAIDs alone through systematic reviews and meta-analyses of RCTs, cohort and case control studies.Methods: A comprehensive literature search was performed in MEDLINE, EMBASE, CENTRAL, TOXILINE and LILACS up to April 2010. We included fully-published studies (RCTs, cohort or case control studies) that assessed the relative risk of serious UGI complications in adults who had received nsNSAIDs concomitantly with clopidogrel for at least 4 weeks, compared to nsNSAIDs alone. 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 ratios (OR) with 95% confidence intervals (CI) with the Mantel-Haenszel and inverse variance method (random effects model). Heterogeneity among studies was considered significant if p<0.10 for the Cochrane Q test. Results: None of the RCTs or cohort studies with nsNSAIDs exposure for at least 4 weeks had assessed the risk of serious UGI complications for patients on nsNSAIDs plus clopidogrel compared to nsNSAIDs alone or clopidogrel alone. There was only one eligible case control study. The estimated OR for serious UGI complications on nsNSAIDs plus clopidogrel compared to nsNSAIDs alone was 2.86 (95% CI 1.62-4.92); the estimatedOR on nsNSAIDs plus clopidogrel compared to clopidogrel alonewas 1.81 (95% CI 1.00-3.22). In the same study the adjusted RR (95% CI) for serious UGI complications for patients on nsNSAIDs alone, on clopidogrel alone and on nsNSAIDs plus clopidogrel compared to patients who did not use any of these medications was 1.78 (1.61-1.97); 1.67 (1.27-2.20) and 2.90 (1.58-5.35), respectively. We also estimated the risk of serious UGI complications with use of clopidogrel alone without considering NSAID use from two casecontrol studies (pooled OR 3.79; 95%CI 2.55-5.66).Conclusions: Limited evidence suggests that concomitant use of nsNSAIDs and clopidogrel for at least 4 weeks increases the risk of serious UGI complications approximately 3-fold compared to use of nsNSAIDs alone. There is a need for prospective studies in this area but despite the paucity of data, these results suggest that patients on co-therapy with nsNSAIDs and clopidogrel are at high risk for serious UGI complications and, therefore, may benefit from gastroprotective strategies.