Owing to the small sample size and relatively low power of their study, it is difficult to draw any firm conclusion from it. antagonists) Physique S8 Summarized estimates of subgroup analysis by use of antiplatelet brokers Physique S9 Summarized estimates of subgroup analysis by use of steroids Physique S10 Summarized estimates of subgroup analysis by use of serotonin reuptake inhibitors BCP-82-285-s001.pdf (702K) GUID:?F769A851-6ADB-425A-83C9-3FA792AC329F Abstract Particular concerns have been raised regarding the association between non\vitamin K antagonist oral anticoagulants (NOACs) and the risk of gastrointestinal bleeding (GIB); however, current findings are still inconclusive. We conducted a Rabbit Polyclonal to ARRDC2 systematic review with a meta\analysis to examine the association between NOACs and GIB in real\life settings. We performed a systematic search of PubMed, EMBASE and CINAHL Plus up to September 2015. Observational studies that evaluated exposure to NOACs reporting GIB outcomes were included. The inverse variance method using the random\effects model was used to calculate the pooled estimates. Eight cohort studies were included in the primary meta\analysis, enrolling 1442 GIB cases among 106?626 dabigatran users (49?486 patient\years), and 184 GIB cases among 10?713 rivaroxaban users (4046 patient\years). The pooled incidence rates of GIB were 4.50 [95% confidence interval (CI) 3.17, 5.84] and 7.18 (95% CI 2.42, 12.0) per 100 patient\years among dabigatran and rivaroxaban users, respectively. The summary risk ratio (RR) was 1.21 (95% CI 1.05, 1.39) for dabigatran compared with warfarin, and 1.09 (95% CI 0.92, 1.30) for rivaroxaban. Subgroup analyses showed a dose\related effect of dabigatran, with a significantly higher risk of GIB for 150?mg b.i.d. (RR?=?1.51, 95% CI 1.34, 1.70) but not for 75?mg b.i.d. or 110?mg b.i.d.. In Lurasidone (SM13496) addition, the use of proton pump inhibitors (PPIs)/histamine H2\receptor antagonists (H2RAs) influenced the association in dabigatran users, whereas this effect was modest among rivaroxaban users. In conclusion, our meta\analysis suggested a slightly higher risk of GIB with dabigatran use compared with warfarin, whereas no significant difference was found between rivaroxaban and warfarin for GIB risk. those from pivotal RCTs. To resolve this issue, we conducted a systematic review with a meta\analysis of published observational studies to clarify the association between NOAC use and GIB, and also to investigate the Lurasidone (SM13496) effects of various factors that may affect GIB risk. Materials and methods The present systematic review was conducted following guidance provided by the Cochrane Handbook 46 and is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta\Analyses (PRISMA) statement 47 for the flowchart of study inclusion and exclusion; and the Meta\analysis Of Observational Studies in Epidemiology (MOOSE) statement 48 for overall reporting. Study definitions The exposure of interest was defined as exposure to NOAC or warfarin in the clinical setting. The different doses of NOACs studied in Lurasidone (SM13496) the present meta\analysis were indication\specific daily doses based on recommendations by the FDA or the European Medicines Agency (EMA) 16, and the outcome was the risk of GIB. In observational studies, GIB was defined as any bleeding in the gastrointestinal tract that was identified through medical records or by International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification (ICD\9\CM or ICD\10\CM) codes, as described in the original literature. The classification of the severity of GIB was based on the description in the original studies 26, 38. Major GIB was defined as a fatal GI haemorrhagic event, or a severe GIB event resulting in hospitalization or even requiring transfusion 26, 38, and the remaining were defined as nonmajor GIB. Data sources and search strategy A systematic literature search was conducted using PubMed, EMBASE and CINAHL Plus with the search strategy: (gastrointestinal ulcer OR peptic ulcer OR gastric ulcer OR duodenal ulcer OR gastrojejunal ulcer OR stomach ulcer OR peptic ulcer disease OR gastrointestinal bleeding OR gastrointestinal hemorrhage OR peptic.