Lahey Cardiologist Authors Major Study Evaluating Cardiac Safety of Controversial Diabetes Drugs

Release Date: 09/28/2007 

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Rose Lewis
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Lahey Cardiologist Authors Major Study Evaluating Cardiac Safety of Controversial Diabetes Drugs

BURLINGTON, MA—Dr. Richard W. Nesto, chair, Department of Cardiovascular Medicine at Lahey Clinic, is the lead author of a major study published in this week's edition of The Lancet that examines the cardiovascular safety of pioglitazone (Actos) and the controversial drug darosiglitazone (Avandia), which has been under scrutiny because of reported side effects. Dr. Nesto's team studied the risk for congestive heart failure (CHF) and death from cardiovascular events in patients with type 2 diabetes who were taking these drugs. These medications, known as TZDs, are effective in controlling sugar levels in diabetic patients but are known to cause weight gain and fluid retention in a small percentage of patients.

The authors felt it was important to determine the cardiac safety of these drugs since controlling blood sugar is a key aspect of treating diabetes, and cardiovascular disease is the most common cause of death in diabetics. Dr. Nesto and colleagues conducted a combined analysis of seven randomized double-blind clinical trials involving 20, 191 patients and measured how many patients with type 2 diabetes taking TZDs developed congestive heart failure or death from cardiovascular causes.

“Despite the effective glucose-lowering effect of TZDs, our data indicates that these drugs should not be used in patients with a history of heart failure and should be used cautiously for glycemic control in patients with cardiovascular disease in whom the absolute risk for CHF is much lower,” said Dr. Nesto. “The use of TZDs should be weighed against the risks and benefits of other antidiabetic medications.”

The researchers found a 72% increase in relative risk for CHF for patients with a variety of variables. They included:

  • Patients with prediabetes and type 2 diabetes but no cardiovascular disease
  • Patients with type 2 diabetes and cardiovascular disease
  • Patients with type 2 diabetes and documented CHF


According to the authors, the absolute risk for CHF varied a great deal across these patient groups. This should help clinicians prescribe TZDs appropriately. The fact that these drugs did not increase the risk of death from cardiovascular causes may indicate that this type of heart failure is more benign than previously thought and should reassure practitioners.

The authors say that since the drug exposures in these trials were relatively short, and most patients did not have previous histories of CHF or evidence of left ventricular dysfunction, the excess of CHF events related to TZDs was probably the result of TZD-related fluid retention in susceptible patients. They add, however, that the natural history of congestive heart failure when caused by TZD-related fluid retention is unknown.

Conclusion
The authors conclude with a note of caution, saying: “Insufficient follow-up durations could have affected our conclusions about the association between CHF and cardiovascular mortality. We also did not have sufficient data to assess whether the risk of congestive heart failure differed between the two TZDs. We need longer follow-up and better characterization of patients in whom CHF develops because of fluid retention to determine the effect of TZDs on overall cardiovascular outcome and whether CHF should be regarded as an adverse event or a characteristic cardiovascular endpoint.” Overall this information should assist practitioners select appropriate patients with type 2 diabetes for TZD treatment.

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Lahey Clinic, a physician-led, nonprofit group practice, is world-renowned for innovative technology, pioneering medical treatment, and leading-edge research. A teaching hospital of Tufts University School of Medicine, the Clinic provides quality health care in virtually every specialty and subspecialty, from primary care to cancer diagnosis and treatment to kidney and liver transplantation.