By: Herb Denenberg, The Bulletin
05/24/2007
Why are a million Americans and many more millions outside of the U.S. taking Avandia (from GlaxoSmithKline), a drug that might increase the risk of cardiac disease and death? The explanation is simple: doctors read and rely on drug company advertising instead of disinterested drug studies; doctors listen to drug company pitchmen instead of disinterested drug researchers; drug companies spend billions to brainwash doctors and patients so they clamor for and prescribe drugs that may be unsafe, ineffective and overpriced for conditions for which there may be drugs that are safer, more effective and lower in price.
All the usual suspects acted surprised when an important new study in the prestigious New England Journal of Medicine found that Avandia, prescribed for type 2 diabetes, increased the chances of heart disease and death. Rep. John Dingell (R-Mich.) and Rep. Henry Waxman (R-Calif.) went into their standard tirade about the FDA and drug companies and called for hearings. These are the same phonies who have been doing their act for many years, while failing to bring about fundamental reform at the FDA. They have enough energy for the initial flurry of publicity but not for the long haul of fundamental reform of the FDA. The New York Times, whose reporting on most matters has become a journalistic joke, reported that the new findings took doctors and Wall Street by surprise. If they were taken by surprise, they've been in a Rip van Winkle slumber for years. The drug company involved went into its usual state of denial, criticizing the study and reaffirming the safety of its product. Many health organizations and the FDA took the standard cop-out: See your doctor. They didn't have good advice for doctors or patients.
Now put the case that the doctors were actually reading the medical literature instead of only paying heed to drug company propaganda and snake oil salesmen, bearing free samples and gifts.
Avandia came on the market in 1999, and The Medical Letter (August 13, 1999) reported, "The long-term benefits and safety of [Avandia, the brand-name] rosiglitzaone [the generic name] for patients with type 2 diabetes remain to be established." Medical Letter also reported that clinical trials of Avandia have only been published in abstract form. Can you believe that? The FDA lets a drug come on the market, and scientists still don't have access to the full clinical studies supposedly demonstrating the drug is safe and effective. That's one of a thousand links proving the FDA and drug companies aren't protecting the public and the patients.
Doctors, unfortunately for patients, don't pay attention to the old maxim of prescribing, "Don't be the first to use a new drug, or the last to use an old one." This maxim has become a prescribing rule for wise doctors, who know to avoid new drugs (unless there is a compelling reason to do otherwise, because they have simply not been tested on a large enough sample to assure their safety and effectiveness). The Health Research Group, author of the best-selling book Worst Pills, Best Pills, recommends a seven-year rule: Avoid new drugs until they have been tested on the market for seven years, unless there is some compelling reason to do otherwise.
One critic of the FDA and the drug industry, Dr. Ray D. Strand, in his book Death by Prescription, says those who take new drugs are participating in "the great clinical trial - you!" In other words, when you take a new drug, you are becoming an unknowing guinea pig. He documents disasters from new drugs such as Lotronex, on the market for less than a year, and pulled off because it was causing serious illness and death.
As soon as Avandia hit the market, the respected monthly, The Medical Letter (August 13, 1999) warned "the long-term benefits and safety" of Avandia for treating type 2 diabetes "remain to be established."
There were other signals of problems with Avandia long before this latest flurry of publicity. On March 21, 2000, Rezulin was withdrawn from the market because of rare but severe liver toxicity. The Medical Letter (April 17, 2000) reported full-page ads urged patients to switch from Rezulin to Avandia. How's that from going from the pharmaceutical frying pan into the fire? At the time, Medical Letter again warned (April 17, 2000) that the long-term safety of Avandia "remains to be established."
But little and big warnings like that don't stop doctors from prescribing and patients from asking for drugs of unproven safety and efficacy. There was another implied warning in the recall of Rezulin. It is a member of the same family as Avandia, which should have raised a red flag or two. When one drug in a family is recalled, that often means others in the same family may be on the way out. That's what happened in the case of Vioxx.
If you need more advance warning, Avandia is one of 181 top-selling drugs that Worst Pills, Best Pills places on its "Do Not Use" list. Even before the Avandia publicity, the Health Research Group (author of the just cited book) had petitioned the FDA to require the package insert to indicate the therapeutic inferiority of the drug compared to other oral diabetics, and to better explain the safety problem with Avandia. To support this, the petition indicated that nine out of 10 studies showed that Avandia and other drugs in its family, so-called glitzazones, came out as inferiors to other anti-diabetic drugs. The petition also pointed out Avandia causes fluid retention, which can lead to difficult breathing and heart failure.
Even before the latest flap, the Avandia package insert indicated that the drug could cause or worsen heart failure says Worst Pills, Best Pills. Despite that and other warnings, a study found that 7.1 percent of patients leaving hospitals who had been there with heart failure got a prescription for Avandia or its brother drug, Actos, although both cause fluid accumulation and carry the same warning. This suggests, as does many other studies, that even warnings are often ignored perhaps due to the heavy selling pressure exerted by the drug companies. In another later study of hospitalized heart failure patients, the use of Avandia and its brother drug had increased to 16.1 percent. That latter study suggest that despite warnings, the situation is only getting worse.
Dr. Ray Strand, whose book is cited above, makes an interesting point in the history of Rezulin, brother drug of Avandia. He said the FDA has a voluntary reporting system, so no one knows for sure what is going on with adverse reactions to drugs. Experts agree only a small fraction of all adverse reactions get reported. So when one does occur, FDA often just changes the labeling. That happened, says Dr. Strand, four times with Rezulin. Finally, in March of 2000, the FDA had to admit a killer drug was on its hands and it recalled Rezulin. Dr. Strand says if you put blind faith in the broken drug system, it may cost you or a loved one their health and life. Incidentally, my guess is the FDA will make some label changes and not recall Avandia.
So warnings were flying from 1999 when Avandia came to market. If that's not enough, consider a few more advance warnings:
At least as early as 2005, the drug company had warned the FDA of a safety problem with Avandia.
Then, it is reported, that the company posted a study on its obscure Web site, indicting Avandia raised patients' heart disease risk by 30 percent. That was only nine months ago.
So did the FDA or the drug company issue a warning to the public? Of course not. Further study is always necessary, until the drugs' dangers are obvious beyond any contradiction. The FDA has a long history of studying such problems to death, yes, the death of the patients.
If that isn't enough to give you the message about this drug, the drug company that makes it, and the FDA, here's one final flick. The FDA doesn't have a recommendation to stop using the drug and getting a substitute or other treatment plan. It says merely don't stop using the drug and consult with your doctor. If the doctors had been paying attention, they wouldn't have been prescribing the drug in the first place. The FDA offers no help for patients or doctors.
Other doctors weren't as chicken-hearted as the FDA. In fact, as indicated, the Health Research Group recommends against the drug (and its brother Actos) and says there are better alternatives. Other doctors have expressed the same view in published reports since the Avandia story broke. An editorial in the New England Journal of Medicine questions why doctors would continue to prescribe Avandia. The editorial stated, "In view of the potential cardiovascular risks and in the absence of evidence of other related advantages, except for laboratory measures of glycemic [blood sugar] control, the rationale for prescribing [Avandia] at this time is unclear." Dr. Steven A. Nissen of the Cleveland Clinic, lead author of the study in the New England Journal of Medicine, denied some who claimed the heart risk was small: "It's a huge risk," he said, noting that an estimated "tens of thousands of people" might have had heart attacks as a result of the drug. Dr. Nissen admits his study has some imperfections, but he stands by it. And remember, he was the one who blew the whistle on Vioxx, getting it recalled, and on another anti-diabetes drug, Pargluva, keeping it off the market altogether.
To further put this matter into perspective, there was a report that GlaxoSmithKline recently settled a lawsuit filed by the attorney general of New York for $2.5 million. The lawsuit accused GlaxoSmithKline of fraudulently withholding some of the results of safety studies on the prescribing of the antidepressant Paxil to children. The company denied the accusations while settling.
The bottom line for those taking Avandia or its brother, Actos:
You don't want to stop taking the drug without getting medical advice first. See your doctor as soon as possible.
You have to decide who you are going to believe. If you believe the critics, you may want to see if your doctor can switch you to another drug that will work for you. That's what Worst Pills, Best Pills suggests.
It is not clear if there is a problem with Actos based on this study. But Actos is a "Do Not Use" drug on the list of Worst Pills, Best Pills.
You may also want to let your elective representatives know that it is about time they fix the FDA.
This might be a good time to reconsider your whole approach to your treatment plan. I'd recommend the section on diabetes in Worst Pills, Best Pills. Make sure that your lifestyle treatment - diet, exercise, sleep and control of stress - is working along with any medication your taking. It makes sense to push lifestyle treatment in an attempt to eliminate the need for medications altogether.
