title: Risk of death and cardiovascular outcomes with thiazolidinediones: a study with the general practice research database and secondary care data.
abstract: OBJECTIVE
  To describe the likely extent of confounding in evaluating the risks of cardiovascular (CV) events and mortality in patients using diabetes medication.
  
  
  METHODS
  The General Practice Research Database was used to identify inception cohorts of insulin and different oral antidiabetics. An analysis of bias and incidence of mortality, acute coronary syndrome, stroke and heart failure were analysed in GPRD, Hospital Episode Statistics and death certificates.
  
  
  RESULTS
  206,940 patients were identified. The bias analysis showed that past thiazolidinedione users had a lower mortality risk compared to past metformin users. There were no differences between past users of rosiglitazone and pioglitazone (adjusted RR of 1.04; 95% CI 0.93-1.18). Current rosiglitazone users had an increased risk of death (adjusted RR 1.20; 95% CI 1.08-1.34) and of hospitalisation for heart failure (adjusted RR of 1.73; 95% CI 1.19-2.51) compared to current pioglitazone users. Risk of mortality was increased two-fold shortly after starting rosiglitazone. Excess risk of death over 3 years with rosiglitazone was 0.3 per 100 in those aged 50-64 years, 2.0 aged 65-74, 3.0 aged 75-84, and 7.0 aged 85+. The cause of death with rosiglitazone was more likely to be due to a disease of the circulatory system.
  
  
  CONCLUSIONS
  Higher risks for death (overall and due to cardiovascular disease) and heart failure were found for rosiglitazone compared to pioglitazone. These excess risks were largest in patients aged 65 years or older. The European regulatory decision to suspend rosiglitazone is supported by this study.
authors.affiliation: General Practice Research Database, Medicines and Healthcare products Regulatory Agency, London, United Kingdom.
authors.forename: Arlene M
authors.initials: AM
authors.lastname: Gallagher
authors.forename: Liam
authors.initials: L
authors.lastname: Smeeth
authors.forename: Suzie
authors.initials: S
authors.lastname: Seabroke
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.forename: Tjeerd P
authors.initials: TP
authors.lastname: van Staa
mesh_terms: D054058:Acute Coronary Syndrome / Q000139:chemically induced; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000209:etiology*; D015331:Cohort Studies; D016208:Databases, Factual; D048909:Diabetes Complications / Q000139:chemically induced / Q000175:diagnosis; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D006333:Heart Failure / Q000139:chemically induced; D006760:Hospitalization; D006801:Humans; D007328:Insulin / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000009:adverse effects; D008875:Middle Aged; D000077205:Pioglitazone; D012306:Risk; D000077154:Rosiglitazone; D020521:Stroke / Q000139:chemically induced; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D000077205:Pioglitazone