Experts -- including the doctor who sounded the Avandia alarm -- tell WebMD there's no need for patients to panic.
Researcher Steven Nissen, MD, is chairman of Cleveland Clinic's cardiovascular medicine department. Nissen, past president of the American College of Cardiology, was one of the first doctors to raise the alarm about the heart risks posed by Vioxx.
Nissen says his findings are valid, but he warns that the data are not definitive and must be confirmed by further studies.
"What patients need to know is there is some evidence of cardiovascular harm from Avandia -- but there is not any reason to panic," Nissen tells WebMD.
Since news of the Nissen study broke on Monday, frightened diabetes patients have flooded their doctors' phone lines, says Luigi F. Meneghini, MD, MBA, director of the diabetes treatment center at the University of Miami.
"The way this has been presented has been completely out of proportion. It has created a lot of hysteria," Meneghini tells WebMD. "Patients have stopped taking their medications. They don't want to be on this medication any more."
Andrew Drexler, MD, director of UCLA's Gonda Diabetes Center, is seeing the same reaction.
"We're definitely getting flooded with calls. Everybody wants to know what to do," Drexler tells WebMD.
So here's what these experts say you should do:
- If you are currently taking Avandia, do not stop taking the drug.
- If you are taking Avandia and have already had a heart attack or heart trouble, call your doctor to schedule an appointment as soon as possible.
If you don't already have a heart problem, the risk from Avandia -- if there truly turns out to be one -- is not so great that you have to see a doctor right away. But do make an appointment to discuss the issue.
Calls for Calm in Wake of Avandia Alarm
At least since 2005, the FDA has been aware of the possible heart attack risk of Avandia. But there's conflicting evidence, including a study of more than 30,000 diabetes patients in a large health maintenance organization (HMO) that found no extra heart attacks among Avandia patients.
For this reason, the FDA has decided not to pull Avandia from the market. Instead, the FDA is working as fast as it can to pull together an expert advisory panel to weigh all the available data.
The FDA warns patients not to stop taking Avandia on their own. Drexler agrees.
"When people read these stories about heart attack risk, they often stop taking their diabetes drugs," he says. "The resulting deterioration of their care can be very detrimental. Everyone says, 'Consult your doctor before stopping any prescribed medication,' but we really must stress this point more strongly."
An editorial released on Wednesday by the editors of the British medical journal The Lancet takes the unusual step of criticizing the NEJM for the "urgency" in the tone of the Nissen paper and an accompanying editorial.
"To avoid unnecessary panic among patients, a calmer and more considered approach to the safety of [Avandia] is needed," the Lancet editors write. "Alarmist headlines and confident declarations help nobody."
Drexler notes that an ongoing study, the RECORD clinical trial, is studying whether Avandia truly causes heart problems. But the study will not be finished until the end of 2008 or 2009, depending on how many patients develop heart disease.
Another study, the ACCORD trial, which is studying outcomes in 10,000 patients with type 2 diabetes, should also reveal the true risks and benefits of Avandia. That trial, too, is years from completion.
GlaxoSmithKline, the company that makes Avandia, says these trials are being monitored by independent safety boards. Patients should be reassured by the fact that these safety boards have seen no reason to stop the studies, says GSK Chief Medical Officer Ronald Krall, MD.
"The data safety monitoring boards have done an interim analysis very recently and have reassured us there is nothing in that analysis that should affect the conduct of the study or be of concern," Krall tells WebMD. "They have looked at the specific issues raised by Dr. Nissen. Because cardiovascular events are the RECORD study endpoints, they have looked at them in great detail."
Calls for Independent Look at Avandia Risk
Drexler says these safety boards should go one step farther and do a separate and specific analysis to ensure that no signal of heart risk has been missed for any group of patients.
"We are interested not just in whether the drug helps some patients, but in whether the drug is riskier for some patients," he says. "If the Nissen paper is valid, you should be able to see these differences by now."
Drexler believes that patient faith in Avandia can only be restored if GSK hands over all the data it has to an outside panel of experts for independent review.
"GSK should ask some organization, preferably the Endocrine Society, to put together a group of scientists chosen by the organization, and open up their files without restriction and let that group study it," he says. "Unless they do that, I think they are going to have a very hard time selling this drug."
GSK's Krall says this is unnecessary as the FDA is already assembling an expert panel. He promises that GSK will make all of its data available to the FDA panel.
"We will try to share everything we have with the community of physicians," he says.
Nissen is skeptical.
"I have been discussing this with GSK, and they do not want to have a complete analysis done of all their data," he says. "If they are going to clear the air, now is the time. The reason they don't want to do it, I think, is they have already done it themselves and don't like the results."
Drexler says GSK's reassurances have so far been more of a public relations effort than a scientific effort. Krall bristles at that suggestion.
"There are a number of scientific manuscripts in preparation, that have been in preparation, that will help communicate to the scientific community the data that the FDA and European regulatory authorities already have seen," Krall says. "All of this is not under GSK control. Some of these studies have been done by external academic experts. It is they who are writing the actual manuscripts. There is an interest in this scientific data, and we are trying to respond as quickly as we can with scientific communications."
"Why do we control blood sugar in diabetes? The reason is to control complications of diabetes," Nissen says. "Avandia has never been shown to control any diabetes complication. They have had eight years to show a health-outcome benefit. Yet they've shown no reduction in microvascular [eye, kidney, and extremity] complications and no reduction in cardiovascular [heart] outcomes."
Krall says such studies began very soon after Avandia approval.
"It takes studies of 10 years' duration or more to show clinical endpoints," he says. "It took 10 years to see clinical results in studies of [the older diabetes drugs] metformin and sulfonylura. It is not fair to expect those results yet for Avandia. What is clear is that if you do manage [blood sugar levels], you do see those endpoints in 10-plus years' time."
Alternatives to Avandia
"It may be hard to justify continuing to prescribe Avandia if there is an alternative, Actos, that does not have same risk profile," Meneghini says. "So in terms of new Avandia prescriptions, I don't think so. It is not so much a clinical decision as a liability decision. Because if a patient says, 'I want to come off the drug,' and his doctors says, 'No, continue taking it,' and the patient has a heart attack -- for whatever reason -- well, you can imagine what comes after that."
But Meneghini still says Avandia is helping some patients.
"In terms of patients currently on the drug, if they have had a good response in terms of blood sugar control, and no prior cardiovascular event, I don't see why they should not continue," he says. "In those with a history of heart trouble, maybe they should consider a change. Insulin therapy is one of the cleanest options we have at this point in time."
And, of course, there are nondrug treatments, too.
"Avandia and Actos reduce insulin resistance. You can achieve that with physical activity and losing weight, especially around the waist," Meneghini says. "These are healthy ways to achieve better blood sugar control without side effects. This should be adopted by anybody. After all, the mainstay of diabetes treatment is healthy weight, healthy diet, and lose some weight if you are overweight."