Elderly patients who started taking rosiglitazone had higher rates of all-cause mortality and hospitalization for heart failure during the following year than did those who started taking pioglitazone, in a study of nearly 30,000 subjects.
Previous research has suggested that rosiglitazone carries greater cardiovascular risks than pioglitazone, but “to date, only sparse information has become available from head-to-head comparisons between these two drugs,” said Dr. Wolfgang C. Winkelmayer and his associates at Brigham and Women's Hospital, Boston.
They conducted such a comparison in a large cohort of elderly patients with recent-onset type 2 diabetes. “To our knowledge, this is the first study specifically aimed at detecting any differences in relative cardiovascular safety between these two thiazolidinediones in typical elderly patients initiating such therapy.”
The study participants were identified using medical claims data that included comprehensive prescription drug coverage for elderly patients throughout New Jersey and Pennsylvania. The 28,361 patients were older than 65 years when they filled their first prescriptions for pioglitazone (50.3%) or rosiglitazone (49.7%) between 2000 and 2005.
The median time of exposure to the drugs was about 1 year. During that time 1,869 people died.
Rosiglitazone users had significantly higher rates of all-cause mortality. Crude, unadjusted event rates per 1,000 person-years were 60 for pioglitazone and 69 for rosiglitazone initiators, which yielded an unadjusted incident rate ratio of 1.17. After adjustment for patient characteristics, a Cox regression showed a 15% greater mortality rate in patients initiated with rosiglitazone compared those who took pioglitazone.
Use of rosiglitazone also was associated with a 13% greater risk of heart failure, Dr. Winkelmayer and his colleagues reported (Arch. Intern. Med. 2008;168:2368-75).
This association remained robust when the data were analyzed in different statistical models, and it was consistent across important subgroups of patients, such as those who had already begun insulin therapy.
The study was limited in that patients were not randomly assigned to the two drugs, but were given them at the discretion of their treating physicians.
In addition, the study didn't include information on cause of death, so although the findings suggested a higher cardiovascular case fatality rate for rosiglitazone, “we cannot formally examine this possibility,” the authors wrote.
Nevertheless, the results “confirm the safety concerns that have been raised for rosiglitazone, compared with pioglitazone,” they added.
Dr. Winkelmayer has participated, without receiving an honorarium, in the advisory boards of Amgen, Roche, Genzyme, and Fresenius Medical Care. This study was supported by the American Heart Association, Satellite Healthcare Inc., and investigator-initiated grants from Amgen, Fresenius, and GlaxoSmithKline.