Avandia not to blame for deaths in trial, U.S. says

WASHINGTON (Reuters) - GlaxoSmithKline's diabetes drug Avandia was not to blame for heart deaths in a trial to see if treating diabetes would reduce heart disease, U.S. government-funded researchers said on Wednesday. They said no single drug appeared to be responsible, and that they would adjust the trial, called ACCORD, so that patients' blood sugar would not be lowered so intensively. The National Heart, Lung and Blood Institute, which funded and helped organize the trial, said it appeared to be the strict lowering of blood sugar, or glucose, that was to blame. Concerns about the safety of Avandia, known generically as rosiglitazone, were triggered in May by a U.S. analysis linking it to a 43 percent higher risk of heart attack. "Because of the recent concerns with rosiglitazone, our extensive analysis included a specific review to determine whether there was any link between this particular medication and the increased deaths. We found no link," Dr. William Friedewald of Columbia University in New York, one of the directors of the trial, said in a statement. "Extensive analyses by ACCORD researchers have not determined a specific cause for the increased deaths among the intensive treatment group. Based on analyses conducted to date, there is no evidence that any medication or combination of medications is responsible," the NHLBI added in the statement. U.S. and European regulators now require strongly worded warnings on the packages of Avandia and similar drugs, cautioning about the heart risks. Avandia was Glaxo's second-biggest drug in 2006, with worldwide revenue of 1.6 billion pounds ($3.2 billion), but sales have plunged since May. WORRYING ANALYSIS The ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial was set up to see if controlling diabetes would reduce the risk of heart disease in patients. Diabetes is known to be a leading cause of many types of heart disease. But in May 2007, Dr. Steve Nissen of the Cleveland Clinic reported in The New England Journal of Medicine that his analysis of other studies suggested Avandia raised the risk of a heart attack by 43 percent. A flurry of warnings followed but groups such as the American Heart Association and the American College of Cardiology urged patients not to worry and not to stop taking Avandia or other, similar drugs such as Takeda Pharmaceutical's Actos without consulting with a doctor. The NHLBI did its own analysis and released a statement on Wednesday saying the drugs themselves were not the problem. "In this trial of adults with type 2 diabetes at especially high risk for heart attack and stroke, the medical strategy to intensively lower blood glucose (sugar) below current recommendations increased the risk of death compared with a less-intensive standard treatment strategy," the NHLBI said. "Study participants receiving intensive blood glucose lowering treatment will now receive the less-intensive standard treatment." The NHLBI, one of the U.S. National Institutes of Health, said 10,251 people were taking part in the ACCORD trial. "Of these, 257 in the intensive treatment group have died, compared with 203 within the standard treatment group. This is a difference of 54 deaths, or 3 per 1,000 participants each year, over an average of almost four years of treatment." But the NHLBI said the death rates were not out of line. "The death rates in both groups were lower than seen in similar populations in other studies," the statement read. Doctors treating the patients in the study could use any U.S. Food and Drug Administration-approved diabetes drug including metformin, thiazolidinediones such as Actos or Avandia, insulins, sulfonylureas, exanatide, and acarbose. Glaxo said the findings appear to raise questions about how aggressively blood sugar should be reduced in managing diabetes. "The same drugs are used in both groups of patients who are either managed aggressively (less than 6 of HbA1c) or to standard blood sugar control (less than 7.5); yet the small increase of events is seen in the group who are aggressively managed," the company said in a statement.