Glaxo's Avandia, Takeda's Actos Increase Heart Risks, JAMA Says

-Bloomberg

12/11/2007 - Older people taking GlaxoSmithKline Plc's Avandia and Takeda Pharmaceutical Co.'s Actos had a higher risk of heart attacks, failure and death than those taking other diabetes pills, a study by Canadian researchers showed. Diabetics over 65 on the drugs were 40 percent more likely to suffer heart attacks, according to a study in the Journal of the American Medical Association. The medicines raised the risk of heart failure by 60 percent, while the likelihood of death increased 29 percent. Avandia increased the risks more than Actos did, possibly because smaller numbers of patients were prescribed the Takeda drug, the researchers said. The findings are similar to those in a May 21 New England Journal report by researchers at the Cleveland Clinic, which found Avandia increased heart attack risks by 43 percent. ``People who were taking these drugs were at higher risks of these outcomes compared to people taking other diabetes pills,'' said Lorraine L. Lipscombe, a researcher at the Institute for Clinical Evaluative Sciences in Toronto, who led the JAMA study. ``We looked at both drugs. Then, when we divided them, we found the risk seemed to be limited to Avandia.'' A separate analysis published in JAMA in September found Avandia increased the chances of having a heart attack by 42 percent, while Actos reduced it. An attack can occur when the heart's oxygen supply is reduced. Avandia and Actos, which belong to a class of drugs called glitazones, already carry U.S. regulators' most stringent warning about heart failure, a condition in which the heart can't pump enough blood. Avandia Sales Avandia was the world's best-selling diabetes pill and London-based Glaxo's second-biggest drug in 2006, bringing in $3.3 billion for the company that year. Since the heart risks were first reported, Avandia sales have fallen by more than half in the U.S. as patients switched to Actos, according to market research firm IMS Health Inc. and Citigroup Inc. analysts. Glaxo shares have declined 11 percent. Lipscombe and her colleagues used patient records from the Ontario Ministry of Health, which collects health-care data on the province's 12.3 million residents, including 1.5 million people over 65. They examined records from 159,000 older people treated with oral diabetes pills and tracked their emergency room visits, hospital admissions and death records, where they occurred, for an average of 3.8 years. The researchers focused on older diabetics because they have the highest prevalence of the disease and tend to be less represented in drugmakers' clinical trials, Lipscombe said. The health ministry funded the study. Additional Attacks ``For every 100 people prescribed the glitazones, we found that over four years there were three additional episodes of heart failure, four additional heart attacks and five additional deaths,'' Lipscombe said. Glaxo said the new JAMA report has ``significant limitations and generates misleading conclusions'' about heart attacks and death. Other long-term, company-funded clinical trials and observational studies showed no increased heart risks, the drugmaker said in a statement. The patients in the Ontario database were more likely to have heart and circulatory disease, suffered more chronic disease than those on Actos, and were four times as likely to develop kidney damage, a sign their diabetes had progressed further, Glaxo said. The U.S. Food and Drug Administration added a so-called black-box warning to Avandia's prescribing information last month, though it called the evidence of heart attack risks ``inconclusive.'' The FDA is continuing to monitor the medicine's safety. Health Canada, the Canadian drug regulator, withdrew approval for Avandia as a stand-alone therapy last month, saying it should be given mainly with the older metformin drug.

An estimated 246 million people, almost 6 percent of the world's adult population, suffer from diabetes and 3.8 million a year die from it, according to the International Diabetes Federation.