title: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong.
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong.
authors.forename: E W
authors.initials: EW
authors.lastname: Chan
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: W K
authors.initials: WK
authors.lastname: Leung
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong.
authors.forename: S
authors.initials: S
authors.lastname: Anand
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong.
authors.forename: I C K
authors.initials: IC
authors.lastname: Wong
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D000925:Anticoagulants / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D016017:Odds Ratio
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000925:Anticoagulants; D002121:Calcium Channel Blockers