The continuing controversy surrounding the cardiovascular risk of the diabetes drug Avandia has led to sharp declines in its use and a surge in sales of the competing drug Actos, in part because the latter is perceived to be safer. Sales of Avandia, as high as $3.4 billion in 2006, have fallen to about $1.1 billion this year, while those of Actos have climbed to about $4.6 billion. But new results reported Monday suggest that the cardiovascular risks of the two drugs are about the same.
Both drugs are members of the family known as thizolidinediones, which decrease the insulin resistance of body tissues and modify the production of cholesterol. They are considered among the most powerful drugs for treating Type 2 diabetes but have been plagued by reports of side effects. A 2007 study of more than 200,000 Medicare patients suggested that Avandia, known generically as rosiglitazone, increased the risk of heart attack, cardiovascular disease, stroke and death by 30% to 40% compared with metformin and other, older diabetes drugs. That study also suggested that the increased risk was not observed with Actos, known generically as pioglitazone.
That study led the Food and Drug Administration to require a stronger warning label on Avandia to alert consumers to the risks. After more reports of increased risk with the drug, an FDA advisory panel last month recommended even stronger warning labels on the Avandia package, although it said that the drug should be kept on the market because the benefits outweigh the potential risks. The panel also recommended that no more patients be enrolled in a prospective study comparing Avandia and Actos directly.
In the new study reported Monday, a team led by Debra Wertz, an outcomes research manager at HealthCore Inc., the research subsidiary of the health insurance company WellPoint Inc., studied the records of 28,938 clients who took either of the two drugs from 2001 to 2005. They obtained information about health outcomes from the company's own records and about deaths from the National Death Index, a database administered by the government's National Center for Health Statistics.
They reported in the journal Circulation: Cardiovascular Quality and Outcomes that, when they accounted for potential confounding effects, including age, gender and prior heart disease, about 4% of each group had a heart attack, heart failure or died. Specifically:
-- 96 patients on Avandia suffered a heart attack, compared with 121 on Actos;
-- 265 on Avandia suffered heart failure, compared with 243 on Actos;
-- 24 on Avandia suffered both heart attack and heart failure, compared with 18 on Actos;
-- and 217 on Avandia and 217 on Actos died.
"What distinguishes this latest study from other claims-based analyses is its analysis of death records, which include out-of-hospital deaths," Wertz said in a statement. The study also followed patients for a longer period of time than earlier studies and the patients were younger, she added. Unlike the earlier studies, however, it did not include strokes in the data, which may account for part of the difference in outcomes.
-- Thomas H. Maugh II / Los Angeles Times