title: Ticagrelor and bradycardia: a nested case-control study.
abstract: OBJECTIVE
  Ticagrelor increases serum adenosine concentrations, slowing conduction and possibly leading to bradycardia. Clinical trial data have shown numerically, though not statistically significantly, higher rates of bradyarrhythmias with ticagrelor versus clopidogrel. Additionally, recent case reports have further raised concerns for this adverse effect. We explored the association between ticagrelor and hospitalization for bradycardia in a real-world setting.
  
  
  METHODS
  We conducted a population-based, nested case-control study of Ontario residents, 66 years of age or older, discharged after a first acute coronary syndrome by linking multiple healthcare databases. Cases included patients hospitalized for bradycardia within 1 year of starting a P2Y12 inhibitor. For each case, we identified 4 controls matched on age, sex, index date, and current use of a P2Y12 inhibitor. The exposure of interest was a prescription for ticagrelor within 90 days, with clopidogrel use as the reference group.
  
  
  RESULTS
  From April 2012 to March 2014, we identified 140 cases and 560 controls who met the study criteria. We found no significant association between bradycardia and exposure to ticagrelor relative to clopidogrel in the previous 90 days prior to the index date (adjusted odds ratio 1.06, 95% confidence interval 0.65-2.21). Further adjustment for potential confounders also did not identify a significant association.
  
  
  CONCLUSIONS
  Among older patients with a first acute coronary syndrome, use of ticagrelor was not associated with a greater risk of admission for bradycardia relative to clopidogrel.
authors.affiliation: Department of Pharmacy, Vancouver General Hospital, Vancouver, BC, Canada.
authors.forename: Ricky D
authors.initials: RD
authors.lastname: Turgeon
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Fernandes
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.|Division of Clinical Pharmacology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Juurlink
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.|Division of Cardiology, Schulich Heart Centre Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: Jack V
authors.initials: JV
authors.lastname: Tu
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.|Applied Health Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mamdani
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives*; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D001919:Bradycardia / Q000139:chemically induced / Q000453:epidemiology*; D016022:Case-Control Studies; D005260:Female; D006299:Health Services for the Aged; D006760:Hospitalization; D006801:Humans; D008297:Male; D009864:Ontario / Q000453:epidemiology; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects*; D000077486:Ticagrelor
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine
keywords: acute coronary syndrome; bradycardia; clopidogrel; myocardial infarction; p2y12 inhibitor; pharmacoepidemiology; ticagrelor