title: Sulfonylurea use and incident cardiovascular disease among patients with type 2 diabetes: prospective cohort study among women.
abstract: OBJECTIVE
  Evidence is inconsistent for the association between sulfonylurea use and risk of cardiovascular disease among patients with diabetes. We aimed to prospectively evaluate this association using the Nurses' Health Study (NHS), a well-established cohort of U.S. women with long-term follow-up.
  
  
  METHODS
  We followed 4,902 women (mean age 68 years) with diabetes (mean duration 11 years), but without cardiovascular disease at baseline. The use of sulfonylureas and other medications was self-reported at baseline and during the follow-up period of up to 10 years. Cox proportional hazards regression models were used to estimate the relative risk (RR) and 95% CI for the association between the sulfonylurea use and incident cardiovascular disease while accounting for potential confounders, including age, diabetes duration, diabetes-related complications, other antihyperglycemic medications, BMI, lifestyle factors, family history of cardiovascular diseases, and present chronic conditions. We also applied the propensity score stratification method to address the possibility of residual confounding.
  
  
  RESULTS
  We identified 339 incident cases of cardiovascular disease, including 191 cases of coronary heart disease (CHD) and 148 cases of stroke. A longer duration of sulfonylurea use was significantly associated with a higher risk of CHD (P for trend = 0.002); the RRs for CHD were 1.24 (95% CI 0.85-1.81) for patients who used sulfonylurea therapy for 1-5 years, 1.51 (0.94-2.42) for 6-10 years, and 2.15 (1.31-3.54) for >10 years, compared with nonusers. Compared with users of metformin monotherapy, the RR for CHD was 3.27 (1.31-8.17) for those who were treated with the combination of metformin and sulfonylurea. The analysis using propensity score stratification yielded similar results. We did not observe a significant association between sulfonylurea therapy and stroke risk.
  
  
  CONCLUSIONS
  Long-term use of sulfonylureas was associated with a significantly higher risk of developing CHD among women with diabetes.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA.
authors.forename: Sylvia H
authors.initials: SH
authors.lastname: Ley
authors.affiliation: U.S. Outcomes Research, Merck, Whitehouse Station, NJ.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Rajpathak
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA Department of Epidemiology, Harvard School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA nhbfh@channing.harvard.edu.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D048909:Diabetes Complications / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D014481:United States
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin