For four years, the study followed patients over age 65, who have the highest rate of type 2 diabetes but aren’t well represented in clinical trials, says lead author Lorraine Lipscombe, a Toronto endocrinologist and researcher at the Institute for Clinical Evaluative Science, funded by the Ontario government.

Lipscombe’s team looked at how patients fared on Avandia or Actos, the only two drugs in their class, compared with those on other diabetes pills.

Since August, the U.S. labels for Avandia and Actos have carried a “black box” warning against their use in patients with advanced congestive heart failure. But the new study found Avandia raised heart failure risk even in patients with no history of the condition, suggesting the heart failure warning doesn’t go far enough, Lipscome’s team writes in The Journal of the American Medical Association.

About 8 percent of patients went to a hospital for congestive heart failure or a heart attack during the study. Compared with patients on other diabetes pills, those on only Avandia or Actos had a 60 percent higher risk of congestive heart failure and a 40 percent higher heart attack risk. They also had a 29 percent higher risk of death.

For reasons not yet clear, the increased heart risks seen in the Avandia/Actos group were predominantly in those on Avandia. That doesn’t mean Actos is safer, Lipscombe says. Her study might have had too few Actos patients – half the number on Avandia – to detect a higher risk, she says.

In observational studies such as this, factors other than the drugs in question might skew results, so clinical trials that randomly assign patients to treatments are considered the gold standard.

“The problems with the study become obvious with regard to the CHF (congestive heart failure) findings,” Nancy Pekarek, spokeswoman for Avandia maker Glaxo-SmithKline, said in an e-mail. “We know (Avandia and Actos) have well-documented and similar CHF events, yet this study somehow finds an increase in these events with Avandia versus Actos.”

But Steven Nissen, the Cleveland Clinic’s chief of cardiovascular surgery, says Lipscombe’s study “has a lot of appeal. It’s independent, it’s not funded by industry, and it’s huge.” And, “it’s real-life data.”

Nissen reported in The New England Journal of Medicine in May the pooled results of 42 short-term clinical trials showed Avandia patients were 43 percent more likely to have a heart attack or be hospitalized for blocked coronary arteries than others in the trials.

Based on Nissen’s study and others, the Food and Drug Administration last month added information to Avandia’s black box about a potential increased heart attack risk. The FDA has asked Glaxo to compare Avandia’s heart attack risk with those of other diabetes pills. That clinical trial is not expected to be done until March 2014.

January 8th, 2008 by RITA RUBIN with APP.com

SOURCE: Avandia Recall › Avandia study shows increased heart risks or death

For four years, the study followed patients over age 65, who have the highest rate of type 2 diabetes but aren’t well-represented in clinical trials, says lead author Lorraine Lipscombe, a Toronto endocrinologist and researcher at the Institute for Clinical Evaluative Science, funded by the Ontario government.

Lipscombe’s team looked at how patients fared on Avandia or Actos, the only two drugs in their class, compared with those on other diabetes pills.

Since August, the U.S. labels for Avandia and Actos have carried a “black box” warning against their use in patients with advanced congestive heart failure. However, the new study found Avandia raised heart failure risk even in patients with no history of the condition, suggesting the heart failure warning doesn’t go far enough, Lipscome’s team writes in The Journal of the American Medical Association.

About 8% of patients went to a hospital for congestive heart failure or a heart attack during the study. Compared with patients on other diabetes pills, those on only Avandia or Actos had a 60% higher risk of congestive heart failure and a 40% higher heart attack risk. They also had a 29% higher risk of death.

For reasons not yet clear, the increased heart risks seen in the Avandia/Actos group were predominantly in those on Avandia. That doesn’t mean Actos is safer, Lipscombe says. Her study might have had too few Actos patients – half the number on Avandia – to detect a higher risk, she says.

In observational studies such as this, factors other than the drugs in question might skew results, so clinical trials that randomly assign patients to treatments are considered the gold standard.

“The problems with the study become obvious with regard to the CHF (congestive heart failure) findings,” Nancy Pekarek, spokeswoman for Avandia maker Glaxo-SmithKline, said in an e-mail. “We know (Avandia and Actos) have well-documented and similar CHF events, yet this study somehow finds an increase in these events with Avandia vs. Actos.”

But Steven Nissen, the Cleveland Clinic’s chief of cardiovascular surgery, says Lipscombe’s study “has a lot of appeal. It’s independent, it’s not funded by industry, and it’s huge.” And, “it’s real-life data.”

Nissen reported in The New England Journal of Medicine in May the pooled results of 42 short-term clinical trials showed Avandia patients were 43% more likely to have a heart attack or be hospitalized for blocked coronary arteries than others in the trials.

Based on Nissen’s study and others, the Food and Drug Administration last month added information to Avandia’s black box about a potential increased heart attack risk. The FDA has asked Glaxo to compare Avandia’s heart attack risk with those of other diabetes pills. That clinical trial is not expected to be done until March 2014.

December 11th, 2007 by Rita Rubin USA TODAY with USA Today

SOURCE: Avandia Recall › New Avandia study reaffirms heart risk

The U.S. Food and Drug Administration (FDA) advised that GlaxoSmithKline, Avandia’s maker, agreed to add the new warning to the existing black box warning. But, despite the revision, the FDA will not withdraw Avandia from the market, claiming that evidence for increased heart attack is inconclusive and does not appear to be higher in Avandia than other type 2 diabetes treatments. In the meantime, the FDA asked GlaxoSmithKline to conduct a long-term study comparing Avandia with other type 2 diabetes drugs. The trial will likely commence in a year; however, full results will not be available until 2014. Patient advocates and FDA critics consider the black box warning a weak response to Avandia’s safety issues and have requested Avandia be pulled from the market.

Avandia breaks down the body’s resistance to insulin but has long been known to cause fluid retention, a major risk factor for congestive heart failure. Evidence does not indicate Avandia and other oral anti-diabetes drugs-thiazolidinediones-prevent cardiovascular risk as a result of reducing blood sugar.

The American Diabetes Association and the European Association for the Study of Diabetes released a revised consensus statement stating that emerging information suggests additional hazards associated with thiazolidedione and rosiglitazone (Avandia) and may result in increased risk of myocardial infarctions. In October, the US Department of Veterans Affairs (VA) announced it was dropping Avandia from its prescription drug formulary stating their review concluded that, in some, Avandia did not afford the same margin of safety as other diabetes medications. The VA accounted for nearly 10-percent of Avandia’s US sales.

In November, Health Canada sent a letter to Canadian health professionals advising Avandia could no longer be prescribed as monotherapy for type 2 diabetes or in combination with sulfonylurea. In May, research based on 42 Avandia studies confirmed a 43-percent increased risk of heart attack among patients taking the drug. In August, Avandia’s warning label was changed to warn that Avandia and others in its class might worsen heart failure.

A Congressional Committee Report found that company executives made a concerted effort to intimidate a diabetes expert into keeping quiet about Avandia’s safety problems, alleging that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved. An internal government memo dated July 16, 2002 analyzed 47 early FDA reports of patients who went into heart failure and required hospitalization while taking Avandia. The report contained warnings from Federal investigators that Avandia might cause heart failure.

Over six million Americans have used the drug to treat adult-onset, or type 2, diabetes and the concern about Avandia is nothing new. The association between Avandia and increased heart failure risk has been known since 1999 when the drug was first approved.

Avandia was Glaxo’s second most popular drug in 2006, with sales of $3.3 billion. Sales have plummeted since publication of evidence linking Avandia with increased risk of heart attack and failure.

November 29th, 2007 by Staff with NewsInferno.com

SOURCE: Avandia Recall › Avandia heart attack controversy results in black box warning