New research shows that diabetics treated with the popular drug Avandia have higher risk of heart failure and death than those taking Actos, leading Canadian scientists to conclude that "continued use of [Avandia]may not be justified."
The findings, published in today's edition of the British Medical Journal, are the latest blow to the controversial blockbuster drug, manufactured by GlaxoSmithKline Inc.
Researchers stressed that the findings are relative and that Actos, a product of Takeda Pharmaceuticals North America Inc., also poses heart risks, albeit lesser ones.
The study, led by David Juurlink, a scientist at the Institute for Clinical Evaluative Sciences in Toronto, involved 39,494 patients over the age of 65 who were prescribed pioglitazone (brand name Actos) or rosiglitazone (Avandia) between 2002 and 2008.
Both medications belong to a class of drugs known as thiazolidinediones (TZDs) and are used to lower blood-sugar levels in patients with Type 2 diabetes. TZDs became popular because they promised better control of blood sugars and fewer heart problems than existing treatments.
But both Avandia and Actos cause fluid retention and heart failure in some patients. Until now, it was unclear if one was safer.
Dr. Juurlink, who is also head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre, said the new research demonstrates that the "cardiac safety profiles" of the two drugs are quite different.
"Given that rosiglitazone lacks a distinct therapeutic advantage over pioglitazone, it's not clear why physicians would continue to prescribe rosiglitazone," he said.
Among the patients in the study, 1,563 were taking Avandia and 895 Actos.
The research team calculated that for every 120 patients treated with Avandia rather than Actos, there would be one additional hospitalization for heart failure. Similarly, an additional death would occur for every 269 patients treated with Avandia rather than Actos. The risk of heart attack caused by both drugs was similar.
Health Canada has already stated that Avandia should not be used as a stand-alone therapy, except by patients who cannot tolerate other diabetes drugs. The U.S. Food and Drug Administration, for its part, has slapped a black box on Avandia's label, the most severe warning the agency can issue.
In 2008, there were 689,051 prescriptions dispensed for Avandia, with a total value of $137-million, and 821,005 prescriptions for Actos, with a total value of $98-million, according to IMS Health Canada, a private company that tracks prescription drugs. The data show that Avandia prescriptions fell by almost half from 2007 to 2008, after high-profile research was published about cardiovascular side effects.
About two million Canadians suffer from diabetes, according to the Canadian Diabetes Association. There are three distinct forms of the disease: gestational diabetes is a temporary condition that occurs during pregnancy; Type 1 diabetes, usually diagnosed in children, occurs when the pancreas is unable to produce insulin; Type 2 diabetes, which accounts for 90 per cent of cases, occurs when the pancreas does not produce enough insulin or the body does not effectively use the insulin it produces.
Rates of Type 2 diabetes rise with age, and about one in four people over the age of 65 have the condition.
When a person is sedentary, overweight and has high blood pressure or high cholesterol, all the vital organs are stressed. This causes the body to make too little insulin and to respond poorly to the little it does make, triggering diabetes.
Fluctuating insulin levels, in turn, cause serious damage to blood vessels. As a result, diabetes is the leading cause of blindness, amputation and kidney failure, and is one of the main causes of cardiovascular disease. To prevent diabetes or control it, blood-sugar levels need to be kept in check.