OBJECTIVE: To analyze the association between pioglitazone use and bladder cancer through a spontaneous adverse event reporting system for medications. RESEARCH DESIGN AND METHODS: Case/noncase bladder cancer reports associated with antidiabetic drug use were retrieved from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) between 2004 and 2009 and analyzed by the reporting odds ratio (ROR). RESULTS: Ninety-three reports of bladder cancer were retrieved, corresponding to 138 drug-reaction pairs (pioglitazone, 31; insulin, 29; metformin, 25; glimepiride, 13; exenatide, 8; others, 22). ROR was indicative of a definite risk for pioglitazone (4.30 [95% CI 2.82–6.52]), and a much weaker risk for gliclazide and acarbose, with very few cases being treated with these two drugs (6 and 4, respectively). CONCLUSIONS: In agreement with preclinical and clinical studies, AERS analysis is consistent with an association between pioglitazone and bladder cancer. This issue needs constant epidemiologic surveillance and urgent definition by more specific studies.

Objectives To assess rates and determinants of treatment discontinuation of or changes in initial antihypertensive drug therapy in a large cohort of patients from Lombardia (Italy). Methods The cohort included 445 356 patients aged 40 –80 years who received their first antihypertensive drug prescription (monotherapy) during 1999–2002. Discontinuation was defined by the absence of any antihypertensive prescription during a 90-day period following the end of the latest prescription. If during the same period a drug of a different class was added or replaced the initial prescription, treatment modification was regarded as combination or switching, respectively. Competing risks methodology was used to estimate and compare cause-specific cumulative incidence. Results Cumulative incidences of discontinuation, combination and switching were respectively 33, 14 and 15% at 6 months, 41, 18 and 17% at 1 year, and 50, 25 and 19% at 5 years since initial treatment. Compared with patients starting treatment with angiotensin-converting enzyme inhibitors, the rate of discontinuation was less for patients on angiotensin receptor blockers with a hazard ratio of 0.92 (95% confidence interval =0.90-0.94), whereas increased discontinuation was observed for patients starting with other drugs, mainly β-blockers with a hazard ratio of 1.64 (1.62-1.67); and diuretics with a hazard ratio of 1.83 (1.81-1.85). Conclusion In the general population of Lombardia, discontinuation of the initial single antihypertensive drug treatment is a common phenomenon, whereas switching to another monotherapy and to combination treatment occur at similarly much lower rates. Blockers of the renin-angiotensin system are associated with the lowest incidence of treatment discontinuation.