Risk of Gastrointestinal Bleeding on Treatment With Statin Alone or With Concomitant Administration of Warfarin: A Systematic Review and Meta-analysis of 5.3 Million Participants.

Abstract

This study aimed to comprehensively evaluate the risk of gastrointestinal bleeding (GIB) with statin monotherapy or with concomitant warfarin use. PubMed, Web of Science, and EMBASE (via Scopus) were searched for observational studies that reported the risk of GIB in adults on statin therapy or with concomitant warfarin use until August 28, 2021. Observational studies evaluating the risk of GIB in adults (age >18 years) on statin medication or concomitant use with warfarin were included. In all, 14 studies with a total of 5 235 123 participants, reporting 48 677 GIB events (43 734 from statin users and 4943 from users of statin combined with warfarin), were included in the analyses. The pooled analysis revealed no difference in the risk of GIB with statin monotherapy (relative risk [RR]: 0.65; 95% CI: 0.42-1.02) or concomitant statin + warfarin use (RR: 0.97; 95% CI: 0.91-1.02). Prior use of statin was not associated with GIB risk (RR: 0.88; 95% CI: 0.63-1.22), whereas a shorter duration of statin use (<5 years) was associated with a lower risk of GIB (RR: 0.42; 95% CI: 0.18-0.97). This analysis provides strong evidence on the association between statin use (with/without warfarin) and risk of GIB. Statin alone or combined with warfarin was not significantly associated with either an increased or decreased risk of GIB. The GIB risk was significantly lower when statins were used for a short duration (<5 years). The putative relationship between statins and GIB in warfarin users warrant further investigation.