title: Pooled analysis of adverse event collection from 4 acute coronary syndrome trials.
abstract: BACKGROUND
  Adverse event collection in randomized clinical trials establishes drug safety. Although costly and regulated, it is rarely studied.
  
  
  METHODS
  Adverse event data from 4 clinical trials (APPRAISE-2, PLATO, TRACER, TRILOGY ACS) comprising 48,118 participants with acute coronary syndromes were pooled to compare patterns and determinants of reporting. Events were classified as serious (SAE) or nonserious (AE) from hospital discharge to 1 year; study end points were excluded.
  
  
  RESULTS
  In total, 84,901 events were reported. Of those, 12,266 (14.4%) were SAEs and 72,635 (85.6%) were AEs. Of all participants, 7,823 (16.3%) had SAEs, 18,124 (37.7%) had only AEs, and 22,171 (46.1%) had neither. Nonserious adverse events were distributed across system organ classes: general disorders (11%), infection (10%), gastrointestinal (10%), respiratory (9%), cardiovascular (8.4%), and other (35%). Serious adverse events had a higher proportion of cardiovascular causes (14.0%). Event reporting was highest after hospital discharge, decreasing rapidly during the following 3 months. In a Cox proportional hazards model, chronic obstructive pulmonary disease (hazard ratio 1.58, 95% CI 1.44-1.74), heart failure (1.55, 1.40-1.70), older age, and female sex were independent predictors of more SAEs, whereas enrollment in Eastern Europe (0.63, 0.58-0.69) or Asia (0.84, 0.75-0.94) were independent predictors of fewer SAEs.
  
  
  CONCLUSIONS
  Half of all participants reported adverse events in the year after acute coronary syndrome; most were AEs and occurred within 3 months. The high volume of events, as well as the variation in SAE reporting by characteristics and enrollment region, indicates that efforts to refine event collection in large trials are warranted.
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: André
authors.initials: A
authors.lastname: Zimerman
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Stebbins
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Patrícia O
authors.initials: PO
authors.lastname: Guimarães
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Ghazala
authors.initials: G
authors.lastname: Haque
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Chiara
authors.initials: C
authors.lastname: Melloni
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Trollinger
authors.affiliation: Uppsala Clinical Research Center, UCR, Uppsala University, Uppsala, Sweden.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Erik Magnus
authors.initials: EM
authors.lastname: Ohman
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Uppsala Clinical Research Center, UCR, Uppsala University, Uppsala, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Brian
authors.initials: B
authors.lastname: Tinga
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pieper
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC. Electronic address: karen.alexander@duke.edu.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Alexander
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications* / Q000401:mortality / Q000628:therapy; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D002170:Canada / Q000453:epidemiology; D004311:Double-Blind Method; D004562:Electrocardiography; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D009204:Myocardial Revascularization / Q000379:methods*; D010351:Patient Discharge; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors