title: Results of a reevaluation of cardiovascular outcomes in the RECORD trial.
abstract: BACKGROUND
  The US Food and Drug Administration (FDA) required a reevaluation of cardiovascular (CV) outcomes in the RECORD trial. This provided an opportunity to assess the implications of event adjudication by 2 groups and quantify the differences as well as to use new FDA end point definitions in development.
  
  
  METHODS
  Original data were used to systematically identify all potential deaths, myocardial infarctions (MIs), and strokes. Site investigators were approached for additional source documents and information about participants lost to follow-up. Suspected events were adjudicated using standard procedures, and the results were compared with the original trial outcomes.
  
  
  RESULTS
  Follow-up for mortality was 25,833 person-years, including an additional 328 person-years identified during the reevaluation effort. A total of 184 CV or unknown-cause deaths (88 rosiglitazone, 96 metformin/sulfonylurea), 128 participants with an MI (68 rosiglitazone, 60 metformin/sulfonylurea), and 113 participants with a stroke (50 rosiglitazone, 63 metformin/sulfonylurea) were included. The hazard ratio (HR) for rosiglitazone versus metformin/sulfonylurea for the end point of CV (or unknown cause) death, MI, or stroke was 0.95 (95% CI 0.78-1.17) compared with 0.93 (95% CI 0.74-1.15) for the original RECORD results. Treatment comparisons for MI (HR 1.13, 95% CI 0.80-1.59) and mortality (HR 0.86, 95% CI 0.68-1.08) were also the same compared with the original RECORD results. Sensitivity analyses were also consistent with the original RECORD results. Analyses using the FDA definitions showed similar results.
  
  
  CONCLUSIONS
  Only a modest number of additional person-years of follow-up were ascertained from this reevaluation of CV end points in RECORD. Observed HRs and CIs from these analyses using the original RECORD or new FDA end point definitions showed similar treatment effects of rosiglitazone compared with the original RECORD results.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. kenneth.mahaffey@dm.duke.edu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Gail
authors.initials: G
authors.lastname: Hafley
authors.forename: Sheila
authors.initials: S
authors.lastname: Dickerson
authors.forename: Shana
authors.initials: S
authors.lastname: Burns
authors.forename: Sandra
authors.initials: S
authors.lastname: Tourt-Uhlig
authors.forename: Jennifer
authors.initials: J
authors.lastname: White
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.forename: John
authors.initials: J
authors.lastname: McMurray
authors.forename: Robert
authors.initials: R
authors.lastname: Bigelow
authors.forename: Philip D
authors.initials: PD
authors.lastname: Home
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D009026:Mortality; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D000077154:Rosiglitazone; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone