Researchers announced the results of the RECORD trial at the American Diabetes Association meeting in New Orleans. The study monitored 2,220 patients who received Avandia (rosiglitazone) as a supplement to metformin, normally the first-line drug in diabetes 2 treatment, or sulphonylurea. 2,227 other patients received a combination of metformin and sulphonylurea without Avandia.

GlaxoSmithKline said the findings confirmed that “cardiovascular hospitalization and cardiovascular death was not statistically different between the two groups after an average of 5.5 years of therapy.”

Philip Home, a professor at Newcastle University in Newcastle Upon Tyne in the UK and chairman of the RECORD trial, said the data “leads us to conclude that rosiglitaone carries no increased risk of overall cardiovascular death or hospitalization compared to the most commonly used diabetes medicines…which have been used for decades.”

However, an editorial by Toronto doctors Ravi Retnakaran and Bernard Zimman in the medical journal The Lancet, in which the RECORD results were published, raised doubts about the study’s accuracy. The doctors wrote that “definitive conclusions about the relation between rosiglitazone and cardiovascular disease remain elusive, owing to study limitations.”

The overall rate of cardiovascular problems in the RECORD patients was unusually low, and ten percent more of the Avandia patients were taking statins – cholesterol fighting drugs that effectively reduce the risk of heart attack.

Moreover, 45 percent of the RECORD participants dropped out of the study at some point, yet Glaxo maintains that the high dropout rate did not influence the results. Doctors Retnakaran and Zimman believe that dropout rate alone compromises the trial’s conclusions.

Steven E. Nissen, M.D. of the Cleveland Clinic said that “it is impossible to assess the safety of a drug when patients are not actually taking it.”

SOURCE: Avandia Recall › Doctors and critics doubt the accuracy of Avandia study

For years, GlaxoSmithKline, the manufacturer of Avandia, enjoyed stellar sales of the diabetes drug. Avandia was GSK’s second-best seller until the results of some studies surfaced that indicated the drug poses serious risks for its users.

In February of 2007, a press release issues by GSK announced a link between female users and increased risk of bone fractures, especially of the upper arms, hands, and feet.

In June of last year, an article in The New England Journal of Medicine reported that Avandia significantly increased the likelihood of heart attacks by 43% and death by cardiovascular diseases by as much as 64% in users.

The news dealt a devastating blow to Avandia. Estimates indicate that annual Avandia profits dropped by a billion pounds (nearly $1.8 billion U.S.). A growing number of lawsuits against GSK and competition from cheaper generics also threaten GSK’s numbers. It could be argued that while additional job cuts save the company some money, those cuts are only necessary to make the company’s numbers more attractive to investors.

According to the Hertfordshire Mercury, a GSK spokeswoman explained the cuts as “part of GSK’s longer-term strategy to ensure that we invest in key areas of future growth and evolve our business to compete effectively in what is a rapidly changing and challenging environment for pharmaceutical companies.”

Translated from CEO-speak, the statement seemingly alludes to all the problems pharmaceutical companies face these days — that they must appear extra-profitable to investors while sustaining aggressive ad campaigns amidst litigation and declining sales.

SOURCE: Avandia Recall › Avandia sales drop hurting GlaxoSmithKline

Grant started taking Avandia two years ago after he was diagnosed with type 2 diabetes. Prior to taking Avandia, he had no history of heart problems. “Grant had never had any problems in the past,” Mark says. “He had a clean bill of health in terms of his heart prior to that. There was no history of heart disease in our family.”

Within a year of being on Avandia, Grant was diagnosed with high blood pressure. Within two years, Grant was diagnosed with 80 percent blockage of his arteries. He required a quadruple bypass surgery. Grant went in for the surgery on a Monday, but experienced some complications and came out of the surgery with a heart fibrillation.
Only three days after the surgery, Grant suffered a massive stroke, which left him paralyzed on his left side and unable to speak. “We don’t know what caused the stroke, but we assume it had something to do with his requiring the operation to begin with,” Mark says.

Furthermore, Grant’s kidneys shut down and he developed swelling on his brain. Luckily, after two days of dialysis, Grant’s kidneys began to function again and he regained his ability to speak three weeks later. However, damage to his brain was about 25 percent.

“The surgeon and the doctor controlling Grant’s diabetes were surprised he was there with blocked arteries, considering his health prior to this,” Mark says. “They couldn’t believe that a 45-year-old had the problems Grant had.”

Some people might think that Grant’s stroke and other problems were caused by complications from the surgery and that Avandia had nothing to do with it. However, would Grant have required the surgery if he had not been on Avandia? Even if Avandia did not directly cause the stroke, it may have been an indirect cause because it pushed Grant’s blood pressure up and started a chain of events that culminated in his stroke.

“Grant will probably never be 100 percent,” Mark says. “He had 25 percent of his brain affected by the stroke. He was an amazing musician, so that’s rough for him. He’s lost a lot of quality of life. Having said that, he’s got a sense of humor and he’s working hard.

“In Grant’s room, a room of eight people, there were four other patients that had open-heart surgery that had also been on Avandia. Something must be going on-some doctors must have an idea of what is going on.

“It’s starting to sound a lot like Vioxx, where statements are made that the risks outweigh the benefits.

“I just want some justice done here for my brother.”

December 22nd, 2007 by Heidi Turner with LawyersandSettlements.com

SOURCE: Avandia Recall › Avandia starting to sound a lot like Vioxx

Avandia’s heart attack link came to light when an analysis of 42 clinical trails published by the Cleveland Clinic in May showed that patients taking the drug had a 43% higher risk of having a heart attack. Just last month, the Food & Drug Administration (FDA) announced the addition of a long-awaited black box warning for Avandia’s increased risk of heart attacks. However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia’s safety issues, and have called on GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market.

Now, it seems that Avandia side effects have reached the general public. That is made clear in a study conducted by scientists at the Institute for Clinical Evaluative Sciences in Toronto, Canada. Researchers there analyzed data for 159,026 older adults who were treated with at least one oral diabetes drug between 2002 and 2005 and were entered in an Ontario healthcare database.

The subjects were followed through March 2006. During an average follow-up period of 3.8 years, 7.9 percent of the patients were hospitalized for congestive heart failure, 7.9 percent were hospitalized for a heart attack, and 19 percent died, according to the researchers’ report in Journal of the American Medical Association. Further analysis revealed that the risks were largely confined to patients who were using Avandia, known generically as rosiglitazone.

The Canadian researchers wrote that their findings “provide evidence from a real-world setting and support data from clinical trials that the harms of thiazolidinediones may outweigh their benefits, even in patients without obvious…cardiovascular disease”.

This latest research does not bode well for Avandia. Earlier this month, pharmacy benefit managers HealthTrans and Prime Therapeutics announced that they would be dropping the controversial diabetes drug from their value-based prescription drug formularies as of January 1, 2008 because of safety concerns.

In October, the Department of Veterans Affairs (VA) announced that it was removing Avandia from its prescription drug formulary because of its heart attack risks. The VA said that it would still make Avandia available for patients who were already taking it and wanted to continue. But the decision means that patients not currently prescribed Avandia will not be able to get it through the VA in the future. Prior to its announcement, the VA accounted for about 8 percent of Avandia sales.

Avandia was once GlaxoSmithKline’s second-biggest selling drug, with worldwide revenue of $3.2 billion in 2006, but sales have plunged since May, with US sales down 48 percent in the third quarter from a year ago.

December 17th, 2007 by Staff with NewsInferno.com

SOURCE: Avandia Recall › Avandia heart attacks seen in general patient population

New research raises the possibility that long-term treatment with rosiglitazone, as Avandia is also called, could lead to osteoporosis. The diabetes drug is used to improved response to insulin.

While bones seem solid, they constantly are being broken down and rebuilt by the body. Researchers found that in mice, the drug increased the activity of the cells that degrade bones, according to a report in this week’s online issue of Nature Medicine.

Avandia recently was labeled with warnings about the risk of heart failure in some patients. GlaxoSmithKline, which markets the drug, already has acknowledged that a study found a higher risk of fractures among women who take the drug. But this report is the first to attempt to explain the link between the drug and fractures.

The finding “has led to a better understanding of the challenges associated with long-term treatment of patients with Type II diabetes,” said Ronald M. Evans of the Salk Institute for Biological Studies in La Jolla, Calif., lead author of the report.

“It also provides a basis for the development of a ‘next generation’ of drug that can specifically dial out this side effect and a new insight into a previously unrecognized aspect of bone physiology that has important medical consequences,” he said in an interview via e-mail.

Nearly 21 million people in the United States have diabetes. Rosiglitazone is widely used in people with Type II, or adult onset diabetes, the most common form of the disease.

Evans said the discovery was fortuitous. Researchers were looking at different aspects of the diabetic mice and did not realize they would be able to change the bone-removing activity.

The assumption had been that more brittle bones in diabetics were the result of a reduced bone-building activity, not increased bone removal.

“Considering the widespread use of these drugs and the known action in people it is surprising that such a key observation had been missed,” he said.

“The long-term use of rosiglitazone should be cautious in patients with higher risk of fractures such as older women,” he added. Using it in combination with anti-osteoporosis drugs could be beneficial, he said.

The research was funded by the Howard Hughes Medical Institute and the National Institutes of Health.

December 3rd, 2007 by Randolph E. Schmid with Associated Press

SOURCE: Avandia Recall › Diabetes drug may increase bone thinning

The reason is that while short term studies have linked Avandia to an increased heart attack risk, longer term studies have been inconclusive.

In the meantime, experts suggest that people with heart disease take something other than Avandia.

November 15th, 2007 by Staff with Health News

SOURCE: Avandia Recall › Confusing new warning label on Avandia

In a floor statement placed in the Senate record, Sen. Charles Grassley also said that safety watchdogs within the federal Food and Drug Administration “several months ago” recommended a “black box” on the drug’s label, the strongest possible warning.It is the first confirmation that the FDA’s own analysis of Avandia shows a similar magnitude of heart attack risks, dangers that were first publicly raised in a medical journal report published earlier this week.

Grassley complained that FDA higher-ups have said they want to wait for results of an ongoing study that will not be available for two more years before making a decision.

“That’s a long time from now when you have millions of Americans taking this drug,” said the statement by the Iowa Republican. “Those numbers seem like a high enough threshold to me for the FDA to warn the American people of the possibility of a problem.”

The FDA has been under fire since Monday’s report came out, attacked by consumer advocates for dropping the ball on drug safety and for taking no stronger action in light of the new warning signs.

Avandia, sold by the British company GlaxoSmithKline PLC, is a blockbuster medication used to treat Type 2 diabetes, the most common form of the disease. More than 6 million people worldwide have taken the drug, whose U.S. sales topped $2.2 billion last year.

On Monday, an analysis led by Cleveland Clinic cardiology chief Dr. Steven Nissen of 42 separate studies on Avandia concluded that it raised the risk of heart attacks by 43 percent, compared to the rates among people taking no or other diabetes drugs. The analysis also indicated that Avandia might increase the risk of heart-related deaths.

GlaxoSmithKline strongly disputes the conclusions. Company officials said that while their own similar analysis suggested a 31 percent greater risk _ information it shared with the FDA as early as 2005 _ more rigorous, albeit smaller, individual studies did not show that.

Critics have accused the FDA of being lax in monitoring drug safety, and some members of Congress scheduled hearings and have subpoenaed key people to appear.

Grassley’s staff has been meeting with FDA staffers and others and gathering documents all week to investigate the issue, said Jill Kozeny, press officer for the Senate Finance Committee, of which Grassley is ranking member.

FDA spokeswoman Julie Zawisza confirmed Thursday the internal analysis that Grassley’s statement revealed, but added, “we have conflicting data” from individual studies, and therefore “are continuing to review the results of GSK’s ongoing trial to determine the actual risk.”

She said she could not discuss “ongoing regulatory matters” like the black box warning that Grassley’s statement says was urged months ago by the FDA’s Division of Drug Risk Evaluation.

As for the number of heart attacks possibly linked to the drug _ as many as 20 a day, Grassley contends _ Zawisza said: “A relationship between the drug and these deaths has not been established. We don’t have data to support such a conclusion.”

Any increase in heart attack risk is especially worrisome for diabetics because two-thirds of them die of heart problems.

About 1 million Americans are currently taking Avandia, which costs from $90 to $170 for a one-month supply. The FDA and diabetes experts are advising users of the medication to talk to their doctors and not to immediately discontinue the drug, which helps keep blood-sugar levels under control.

May 24th, 2007 by Marilynn Marchione with The Associated Press

SOURCE: Avandia Recall › FDA study said to show Avandia risk