The most dangerous side effects of the type 2 diabetes drug Avandia are congestive heart failure and heart attacks. Despite several studies that show the dangers of the drug, its maker maintains the drug is safe.
Ever since Avandia, manufactured by GlaxoSmithKline, hit the market in 1999, there has been a debate over its suspected association with heart-related disease and death. While some studies have been inconclusive, others present compelling clinical evidence demonstrating that Avandia does cause or exacerbate myocardial infarctions (heart attacks), congestive heart failure and other adverse heart-related events.
Avandia (rosiglitazone) is a member of the class of drugs known as thiazolidinediones or glitazones, used to treat type 2 diabetes. It was one of the best-selling drugs in the world — racking up $3.2 billion in sales in 2006 — before its heart risks were publicized and doctors turned to its rival drug Actos instead. Actos, however, has also been linked to congestive heart failure, and both Avandia and Actos now carry a black-box warning for their risks to the heart. In addition, the FDA severely restricted access to Avandia for several years.
Heart Attack and Congestive Heart Failure
Up to 100,000 heart attacks are blamed on Avandia, according to a scientist with the Food and Drug Administration (FDA). According to clinical studies, the drug increases heart attack risk by 43 percent and can double heart failure risk after one year of usage. It’s important to note the differences between heart attacks and heart failure.
A heart attack occurs when the flow of oxygen-rich blood to a section of the heart muscle becomes blocked, causing the heart muscle to die if the blockage isn’t treated quickly.
Avandia heart attack symptoms include:
- Chest pain or discomfort
- Upper body discomfort in one or both arms, neck, jaw or upper part of the stomach
- Shortness of breath
- Nausea or vomiting
- Cold sweat
Heart attacks can be mild or lethal. Long-term prognosis for both the length and quality of life after a heart attack depends on its severity, the amount of damage sustained by the heart muscle, and the preventive measures taken afterward.
Congestive heart failure is a condition in which the heart is unable to pump enough blood to satisfy the needs of the body, resulting in the accumulation of fluid in the lungs, kidneys, liver or extremities. If left untreated, congestive heart failure will eventually affect every organ in the body. With treatment, the survival rate is 70 to 80 percent. The symptoms of congestive heart failure vary, but can include fatigue, diminished exercise capacity, shortness of breath and swelling.
What Did GlaxoSmithKline Know and When?
From the beginning, GlaxoSmithKline has maintained that Avandia is safe and effective when used “appropriately.” And yet, not only have independent researchers claimed just the opposite over the course of a decade of clinical analysis, but GSK’s own studies revealed Avandia’s heart-related risks.
Company documents uncovered by The New York Times in 2010 revealed that in 1999, GSK set out to determine if Avandia was safer for the heart than Actos. Not only was Avandia found to be no better than Actos, it was actually riskier. But instead of publishing the study’s outcomes, the company spent the next 11 years trying to cover them up, according to The Times investigation.
Later, GSK would be accused by the U.S. Senate of failing to report another company-sponsored study, completed in November 2003, in which patients given Avandia had far more heart problems than those given placebos. The Senate investigation also revealed that GSK’s own 2006 meta-analysis of dozens of Avandia studies established that the drug increased the risk of serious heart problems by nearly a third.
Avandia and the FDA’s Role
But most of the heart risks would remain hidden from the public for several more years — until Dr. Steven Nissen, a Cleveland Clinic cardiologist, published an article in the New England Journal of Medicine in 2007. Based on GSK data, Nissen concluded that Avandia increased the risk of heart attacks by more than 40 percent. In response, the FDA held a special advisory committee meeting on the drug’s health risks. While the agency decided to keep Avandia on the market, it did order a black-box warning on Avandia’s label.
In July 2010, the FDA held another advisory panel on the heart risks of Avandia, in response to a growing body of research suggesting that the drug may have caused thousands of deaths due to heart failure, as well as revelations from the Senate investigation suggesting that GSK knew of the drug’s hazards yet tried to hide them. This time, however, based on the panel’s advice, government regulators decided to restrict access of Avandia to patients already taking it and to new patients, but only if they are made aware by their physicians of the drug’s substantial risks to the heart.
At the same time, the FDA ordered GSK to suspend its Thiazolidinedione Intervention in Vitamin D Evaluation (TIDE) trial, which the FDA had required in 2007. The trial aimed to compare the number of heart attacks, strokes and heart-related deaths among patients given Avandia, Actos or a placebo, but the FDA ended it on ethical grounds.
In late 2013, the FDA reversed course and removed the restrictions on Avandia.
Latest Studies Linking Avandia to Heart Problems
Recent studies have reinforced the link between Avandia and heart problems. In 2010, a study of more than 227,000 Medicare beneficiaries ages 65 or older who were treated with either rosiglitazone (Avandia) or pioglitazone (Actos) from July 2006 to June 2009 found that Avandia led to an increased risk of stroke, heart failure and acute myocardial infarction.
A 2011 meta-analysis of observational studies in the United Kingdom involving 810,000 patients taking either rosiglitazone or pioglitazone provided more evidence that Avandia is associated with a higher risk of heart failure, myocardial infarction and death than Actos.