Diabetes drugs increase risk of heart failure but not death
Saturday, 29 September 2007
Elizabeth Cooney
Certain diabetes drugs should be used with caution in people who have heart disease or a history of heart failure, researchers from the Lahey Clinic report after analyzing previous studies, a finding they hope will clarify the debate on treatment.
Dr. Richard W. Nesto and his colleagues reviewed the results of seven randomized clinical trials that enrolled a total of 20,000 patients to study Actos and Avandia, two drugs from the class called thiazolidinediones, or TZDs, that lower blood sugar. Their article in tomorrow's Lancet concludes that while TZDs do increase by 72 percent the relative risk of heart failure in people who have type 2 diabetes or are close to it, the drugs do not raise the risk of cardiovascular death. The risk of heart failure was already known.
"I view this as helpful information because if doctors want to use this drug even despite the recent debate about it, they can more appropriately select patients for the drugs in whom the risk of heart failure would be very, very low," Nesto, who is Lahey's chair of cardiovascular medicine, said in an interview.
The Lahey report follows another review article by Dr. Steven E. Nissen of the Cleveland Clinic published in June in the New England Journal of Medicine. That analysis found a significant increase in the risk of heart attack for people taking Avandia and a borderline-significant risk of cardiovascular death. The US Food and Drug Administration added a warning to the label for Avandia in August.
Nesto said the data his group examined were more robust than the results Nissen analyzed. A panel of experts judged whether heart attacks occurred in the studies Nesto chose, and all the studies had been previously published.
"We did not find an increase in cardiovascular death despite the increased risk of heart failure and despite the findings of the other meta-analysis that there was a trend toward an increase in the risk of death," Nesto said. "I'm hopeful that this information will help clinicians if they want to use TZDs to more carefully select appropriate patients."
The drugs are still effective at lowering blood sugar, he said. Older drugs that reduce blood sugar have not raised the same degree of concern about cardiovascular side effects, but "these other drugs have not come under the degree of scrutiny that TZDs have," he said.
In a comment that appears in the Lancet, Dr. John G.F. Cleland and Stephen L. Atkin of the University of Hull in England criticize the use of blood sugar levels as a surrogate marker for how well drugs work, rather than patient outcomes such as quality of life and survival.
"All the meta-analyses consistently fail to spot the elephant in the room," they write. "Treatments should be effective rather than merely innocuous."
In a second comment, Dr. Victor Montori of the Mayo Clinic says using surrogate markers represent a false economy in drug testing.
"Patients and society may end up paying dearly for drugs that cause more harm than good," he writes.
An editorial urges drug makers to do post-marketing studies on the long-term effects of drugs.
"Regulatory agencies must hold manufacturers' feet to the fire to ensure that these are performed," it says. "Unless limitations on the understanding, analysis, and communication of drug safety issues are addressed, the TZDs will simply become the latest in a series of preventable drug disasters."
Nesto said he had not read the comments or the editorial.
"The fact remains that the target of treatment in diabetes patients is still the control of blood sugar," he said.
Certain diabetes drugs should be used with caution in people who have heart disease or a history of heart failure, researchers from the Lahey Clinic report after analyzing previous studies, a finding they hope will clarify the debate on treatment.
Dr. Richard W. Nesto and his colleagues reviewed the results of seven randomized clinical trials that enrolled a total of 20,000 patients to study Actos and Avandia, two drugs from the class called thiazolidinediones, or TZDs, that lower blood sugar. Their article in tomorrow's Lancet concludes that while TZDs do increase by 72 percent the relative risk of heart failure in people who have type 2 diabetes or are close to it, the drugs do not raise the risk of cardiovascular death. The risk of heart failure was already known.
"I view this as helpful information because if doctors want to use this drug even despite the recent debate about it, they can more appropriately select patients for the drugs in whom the risk of heart failure would be very, very low," Nesto, who is Lahey's chair of cardiovascular medicine, said in an interview.
The Lahey report follows another review article by Dr. Steven E. Nissen of the Cleveland Clinic published in June in the New England Journal of Medicine. That analysis found a significant increase in the risk of heart attack for people taking Avandia and a borderline-significant risk of cardiovascular death. The US Food and Drug Administration added a warning to the label for Avandia in August.
Nesto said the data his group examined were more robust than the results Nissen analyzed. A panel of experts judged whether heart attacks occurred in the studies Nesto chose, and all the studies had been previously published.
"We did not find an increase in cardiovascular death despite the increased risk of heart failure and despite the findings of the other meta-analysis that there was a trend toward an increase in the risk of death," Nesto said. "I'm hopeful that this information will help clinicians if they want to use TZDs to more carefully select appropriate patients."
The drugs are still effective at lowering blood sugar, he said. Older drugs that reduce blood sugar have not raised the same degree of concern about cardiovascular side effects, but "these other drugs have not come under the degree of scrutiny that TZDs have," he said.
In a comment that appears in the Lancet, Dr. John G.F. Cleland and Stephen L. Atkin of the University of Hull in England criticize the use of blood sugar levels as a surrogate marker for how well drugs work, rather than patient outcomes such as quality of life and survival.
"All the meta-analyses consistently fail to spot the elephant in the room," they write. "Treatments should be effective rather than merely innocuous."
In a second comment, Dr. Victor Montori of the Mayo Clinic says using surrogate markers represent a false economy in drug testing.
"Patients and society may end up paying dearly for drugs that cause more harm than good," he writes.
An editorial urges drug makers to do post-marketing studies on the long-term effects of drugs.
"Regulatory agencies must hold manufacturers' feet to the fire to ensure that these are performed," it says. "Unless limitations on the understanding, analysis, and communication of drug safety issues are addressed, the TZDs will simply become the latest in a series of preventable drug disasters."
Nesto said he had not read the comments or the editorial.
"The fact remains that the target of treatment in diabetes patients is still the control of blood sugar," he said.