title: Incidence of cardiovascular events in which 2 thiazolidinediones are used as add-on treatments for type 2 diabetes mellitus in a Taiwanese population.
abstract: BACKGROUND
  Thiazolidinediones (TZDs) are oral antihyperglycemic drugs that are used to treat insulin resistance. Rosiglitazone is a TZD that has been found to increase the risk of cardiovascular events, especially of myocardial ischemic events.
  
  
  OBJECTIVE
  The aim of this study was to conduct a direct comparison of TZDs (pioglitazone and rosiglitazone) and their relationship to cardiovascular events (myocardial infarction [MI], angina, congestive heart failure [CHF], and cerebral vascular accident [CVA]) in Taiwanese patients with type 2 diabetes mellitus (DM).
  
  
  METHODS
  A retrospective study with second data analysis was performed from January 1, 1998, to December 31, 2006. We selected those who were prescribed only 1 kind of TZD for at least 120 days in the 180-day period; those who switched to another TZD during the above-mentioned periods and had cardiovascular events before the use of TZD were excluded. Stringent definitions for MI, angina, CHF, and CVA were set, and survival analysis was performed.
  
  
  RESULTS
  A total of 7725 type 2 DM cases were included in the final analysis. In our model, the hazard ratio (HR) for development of MI in rosiglitazone-treated patients was 0.539 (95% CI, 0.327-0.889; P = 0.015) compared with pioglitazone-treated patients for whom age, gender, medical specialist, duration of DM, and histories of antihypertensive, statin, and fibrate medications were controlled. There were no significant differences in HRs among angina (HR = 0.543; 95% CI, 0.293-1.006; P = 0.052), CHF (HR = 0.820; 95% CI, 0.619-1.086; P = 0.166), and CVA (HR = 0.949; 95% CI, 0.724-1.244; P = 0.705) groups. Antihypertensive and statin therapy led to significantly different HRs for cardiovascular events depending on when they were first prescribed. If statins were prescribed after TZD, the HR relative to patients who never used statins was 3.896 for MI (95% CI, 2.071-7.328; P < 0.001), 3.194 for angina (95% CI, 1.514-6.737; P = 0.002), and 1.303 for CHF (95% CI, 1.011-1.678; P = 0.041). If antihypertensives were prescribed after TZD, the HR relative to patients never treated with antihypertensives was 7.654 for angina (95% CI, 1.922-32.921; P = 0.004), 3.900 for CHF (95% CI, 2.437-6.242; P < 0.001), 2.242 for CVA (95% CI, 1.613-3.116; P < 0.001), and 2.325 for MI (95% CI, 1.109-4.873; P = 0.026).
  
  
  CONCLUSIONS
  Our data suggested that, as an add-on treatment for diabetic patients, rosiglitazone had significantly lower HRs for MI compared with those for pioglitazone. Diabetic hypertensive patients treated with TZD were at a high risk for angina, CHF, CVA, and MI, whereas statin use increased the risk for MI, angina, and CHF. There are some potential limitations to this study owing to the analysis methodology and retrospective design. In addition, all enrolled type 2 DM patients were treated with TZD medications, but diabetes patients treated with nonpharmacologic therapy, including lifestyle modifications, were not included.
authors: Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Chung-Ching
authors: CC
authors: Wang
authors: Wei-Liang
authors: WL
authors: Chen
authors: Tung-Wei
authors: TW
authors: Kao
authors: Yaw-Wen
authors: YW
authors: Chang
authors: Ching-Hui
authors: CH
authors: Loh
authors: Chin-Chieh
authors: CC
authors: Chou
authors: Chih-Chieh
authors: CC
authors: Chou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000139:chemically induced / Q000453:epidemiology; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000453:epidemiology; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D000077205:Pioglitazone; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000077154:Rosiglitazone; D013624:Taiwan / Q000453:epidemiology; D045162:Thiazolidinediones / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone