Older Patients Face Higher Mortality, With Rosiglitazone Over Pioglitazone

Older diabetic patients treated with rosiglitazone are at higher risk of dying or developing heart failure than patients treated with pioglitazone, a new analysis of Medicare beneficiaries suggests.

The observational study–the largest of its kind to date and is likely to fan the ongoing controversy over the adverse-effect profile of rosiglitazone as compared with other drugs in the thiazolidinedione (TZD) class.

 

Dr Wolfgang C Winkelmayer (Brigham and Women’s Hospital, Boston, MA), lead author on the study, stated that,  while the analysis was observational and retrospective, patients and physicians should nonetheless consider the findings on top of previous research in making decisions about treatment.

For their study, they looked at more than 28 000 diabetic patients over age 65 and followed them for a total of 29 060 person-years. The analysis was restricted to patients who stayed on the drug they’d initially been prescribed, without switching over to another agent. Over the study period–January 1, 2000 to December 31, 2005–1869 patients died.
In the study’s primary analysis, which assumed that patients were exposed to the drug for just 60 days after the date of their most recently filled prescription (and adjusted for patient characteristics), diabetic patients initially treated with rosiglitazone had a 15% higher mortality rate than patients on pioglitazone. Rates of first hospitalization for congestive heart failure–a known side effect of TZDs–were 13% higher in the rosiglitazone group than in the pioglitazone group. In contrast to recent studies pointing to a risk of ischemic events with rosiglitazone, rates of MI and stroke were no different between the groups.
In a secondary analysis, which assumed patients to be exposed on a constant basis to either drug, the mortality findings for rosiglitazone were, in the authors’ words, “less pronounced” for both all-cause mortality (8% higher), and time to first hospitalization for heart failure (11% higher).

But more important, he notes, “The flavor of the finding is the same whether you use one approach or the other approach. In both cases, mortality was elevated, and, in both cases, hospitalization for heart failure was elevated. So there’s no discussion of whether there is a risk or not, it was just the magnitude that was different.”

Winkelmayer added that he was surprised not to see an increased risk of stroke or MI in the rosiglitazone group–an increased risk of ischemic events was seen in last year’s meta-analyses of randomized clinical trials. But he pointed out that, in this study, average patient age was 76, much older than that of patients included in the randomized trials. As such, patients in this Medicare cohort may have actually died from MI or stroke, meaning that their events would not have been recorded in the Medicare records, and any difference between the two drug groups may not have been adequately captured.

But Winkelmayer believes the results, despite being nonrandomized, are powerful enough to be considered by doctors and their patients. Indeed, he points out, patient characteristics in the study were so closely matched at baseline that they actually resemble those of a randomized clinical trial–selection bias was likely limited, he suggested, since both drugs appeared on the market within months of each other and at the time were viewed as more or less equivalent. “The main driver of whether a patient was put on one drug or the other was probably practitioner preference, likely based on which drug rep came through the door last,” he said.

Archives of Internal Medicine, Nov. 24th, 2008