Systematic review with meta-analysis: The association between the use of calcium channel blockers and gastrointestinal bleeding

Abstract

Background Due to their potential anti-platelet effect, it is suggested that calcium channel blockers (CCBs) are associated with gastrointestinal bleeding (GIB). However, results from previous studies are conflicting. Aim To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) and observational studies to clarify the association between CCBs and GIB. Methods We conducted a systematic search of PubMed, EMBASE, Cochrane library and Trial Register databases up to January 2015. Studies that evaluated exposure to CCBs reporting GIB outcomes were included in the meta-analysis. The inverse variance method with random effects model was used to calculate the pooled estimates. Results Seventeen studies (four RCTs, eleven case-control and two cohort studies) were included in the meta-analysis. The summary risk ratio (RR) for GIB was 1.17 (95% CI 1.01-1.36) for CCB users vs. non-users. Subgroup analysis showed that CCB use was associated with a moderately higher risk of lower GIB (RR = 1.83, 95% CI 1.17-2.84) but not upper GIB. However, data from four RCTs did not support association between CCBs and GIB (RR = 0.93, 95% CI 0.82-1.05). Subgroup analyses further showed that the increased risk of GIB among CCB users was only observed in studies that failed to adjust for prior history of GIB (RR = 1.67, 95% CI 1.34-2.08) or use of anti-ulcer drugs (RR = 1.40, 95% CI 1.19-1.65). Conclusion Our meta-analysis showed a marginal association between calcium channel blocker use and the risk of gastrointestinal bleeding. This association is of dubious clinical significance, as the effects of different comparators or adjustment for confounding factors render this association nonsignificant.