title: Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison.
abstract: OBJECTIVE
  There are concerns regarding increased risk of acute coronary syndrome with dabigatran. We aimed to assess whether alternative treatment options such as rivaroxaban or apixaban carry a similar risk as compared with dabigatran.
  
  
  METHODS
  We searched MEDLINE and EMBASE for randomized controlled trials of apixaban, dabigatran or rivaroxaban against control (placebo, heparin or vitamin K antagonist). We pooled odds ratios (OR) for adverse coronary events (acute coronary syndrome or myocardial infarction) using fixed effect meta-analysis and assessed heterogeneity with I(2) . We conducted adjusted indirect comparisons to compare risk of adverse coronary events with apixaban or rivaroxaban vs. dabigatran.
  
  
  RESULTS
  Twenty-seven randomized controlled trials met the inclusion criteria. Dabigatran was associated with a significantly increased risk of adverse coronary events in pooled analysis of nine trials (OR 1.45, 95% CI 1.14, 1.86). There was no signal for coronary risk with apixaban from nine trials (pooled OR 0.89, 95% CI 0.78, 1.03) or rivaroxaban from nine trials (pooled OR 0.81, 95% CI 0.72, 0.93). Overall, adjusted indirect comparison suggested that both apixaban (OR 0.61, 95% CI 0.44, 0.85) and rivaroxaban (OR 0.54; 95% CI 0.39, 0.76) were associated with lower coronary risk than dabigatran. Restricting the indirect comparison to a vitamin K antagonist as a common control, yielded similar findings, OR 0.57 (95% CI 0.39, 0.85) for apixaban vs. dabigatran and 0.53 (95% CI 0.37, 0.77) for rivaroxaban vs. dabigatran.
  
  
  CONCLUSIONS
  There are significant differences in the comparative safety of apixaban, rivaroxaban and dabigatran with regards to acute coronary adverse events.
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK.
authors.forename: Yoon K
authors.initials: YK
authors.lastname: Loke
authors.forename: Shiva
authors.initials: S
authors.lastname: Pradhan
authors.forename: Jessica Ka-Yan
authors.initials: JK
authors.lastname: Yeong
authors.forename: Chun Shing
authors.initials: CS
authors.lastname: Kwok
mesh_terms: D054058:Acute Coronary Syndrome / Q000139:chemically induced*; D000991:Antithrombins / Q000009:adverse effects*; D001562:Benzimidazoles / Q000009:adverse effects*; D000069604:Dabigatran; D065427:Factor Xa Inhibitors / Q000009:adverse effects*; D006801:Humans; D009025:Morpholines / Q000009:adverse effects*; D011720:Pyrazoles / Q000009:adverse effects*; D011728:Pyridones / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D000069552:Rivaroxaban; D013876:Thiophenes / Q000009:adverse effects*; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D009025:Morpholines; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; D015091:beta-Alanine; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: acute coronary syndrome; apixaban; dabigatran; rivaroxaban