title: Association Between Bisphosphonates Therapy and Incident Myocardial Infarction: Meta-analysis and Trial Sequential Analysis.
abstract: BACKGROUND
  Bisphosphonates have shown potential to inhibit atherosclerosis in animal experiments; however, whether bisphosphonates therapy lowers the risk of incidence of myocardial infarction (MI) is debated. We performed the meta-analysis and trial sequential analysis (TSA) to investigate the relation between bisphosphonates therapy and incident MI.
  
  
  METHODS
  Pubmed and Embase databases were systematically searched in April 2015 to identify studies, which compared the incidence of MI in subjects receiving bisphosphonates with that in subjects not receiving the agents. Meta-analysis was conducted using random effects model in consideration of statistical heterogeneity between studies. Reliability of the results from meta-analysis was examined using TSA.
  
  
  RESULTS
  Six observational studies (n = 440261) and 3 randomized control trials (RCTs, n = 11,024) met the eligible criteria. In the pooled analysis of observational studies, bisphosphonates therapy was not associated with reduced risk of MI either using unadjusted estimates (relative risk 0.93, 95% confidence interval (CI), 0.75-1.15) or estimates adjusted for confounding factors (hazard ratio 1.01, 95% CI, 0.84-1.21). Furthermore, hazard of incident MI did not differ between alendronate users and nonusers. TSA showed that evidence from observational studies firmly precluded the association between bisphosphonates and incident MI. Pooled analysis of RCTs also suggested no benefits of decrease in incident MI associated with bisphosphonates therapy (relative risk 1.05, 95% CI, 0.53-2.09). However, TSA demonstrated that evidence from RCTs was insufficient to draw a conclusion.
  
  
  CONCLUSIONS
  Despite the encouraging findings from animal studies, bisphosphonates therapy is not associated with reduced risk of MI.
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Bao-tao
authors.initials: BT
authors.lastname: Huang
authors.forename: Fang-yang
authors.initials: FY
authors.lastname: Huang
authors.forename: Yi-yue
authors.initials: YY
authors.lastname: Gui
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Kai-sen
authors.initials: KS
authors.lastname: Huang
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhi-liang
authors.initials: ZL
authors.lastname: Zuo
authors.forename: Yan-biao
authors.initials: YB
authors.lastname: Liao
authors.forename: Tian-li
authors.initials: TL
authors.lastname: Xia
authors.forename: Shi-jian
authors.initials: SJ
authors.lastname: Chen
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Pu
authors.forename: Mao
authors.initials: M
authors.lastname: Chen
mesh_terms: D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D016017:Odds Ratio; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D004164:Diphosphonates