Multaq, A Fraudulently Approved Heart Drug, Is Killing People

Another drug is killing people. There's no reason for surprise, though. The testing process showed what was wrong. The dangers were predictable.

by Heidi Stevenson

17 January 2011

Again and again, drugs approved by the FDA based on bad studies are found to kill people. The latest is Sanofi-Aventis's Multaq. They have just sent a warning to doctors that it's associated with deadly liver disease. During the approval process, they were, of course, abetted by the FDA, once again demonstrating that the agency works for the benefit of Big Pharma, not patients.

Sold as a drug to smooth out irregular heartbeat, Multaq—generically called dronedarone—was initially unable to get through trials. Of course, when there's a profit to be made, no stone is left unturned. Sanofi-Aventis worked up a study designed to avoid showing the risks. In spite of the previous trials that documented its dangers, the FDA made it available for profiteering.

Are the people at the FDA stupid or lazy? Frankly, I don't think so. They're owned by Big Pharma—at least, too many of those in positions of power are. Some have proven themselves to be conscientious in their support of the public's health. However, when the Director of the Center for Drug Evaluation and Research, Janet Woodcock, MD, coauthors pharmaceutical-financed studies while employed by there, it's obvious that the arrangement between Big Pharma and the FDA is cozy.

The excuse used for approving Multaq was that the most commonly used drug had known safety issues. In other words, because the most popular drug was known to be unsafe, that made it okay to authorize use of another unsafe drug. The logic appears to be that two bads equal a good.

Multaq's Trial History

First Three Studies

In 2003, Sanofi-Aventis stopped its ANDROMEDA trial for Multaq. The reason was simple. Too many patients were dying. Two other trials, EURIDIS (European) and ADONIS (North & South America, South Africa, and Australia) claimed benefit. Like the ANDROMEDA trial, they were financed by Sanofi. The doctor who led the trials, Bramah N. Singh, MD, DSc, collects signficant sums from Sanofis-Aventi and other pharmaceutical firms, including GlaxoSmithKline, for consulting and lecturing.

The EURIDIS and ADONIS trials did not include patients with the most severe cases of heart disease, because they had already been found to die from taking Multaq. The end point of those trials was length of time until atrial fibrillation occurred, up to a maximum of one year. Whether this actually amounted to lengthening of life was not considered.

Singh reported more than doubling of the length of time for an episode of atrial fibrillation. That sounds really good—but it doesn't note that subjects who took the drug dropped out at more than double the rate of those who took placebo. However, because they used a modified intention-to-treat method of reporting, those who dropped out were included in the results! Nonetheless, the study found significantly higher levels of serum creatinine, a strong indicator of severe liver dysfunction.

The author found that Multaq was effective. His conclusion stated:

In conclusion, our trials showed that the rates of the first recurrence of atrial fibrillation and of the first symptomatic recurrence at 1 year were significantly reduced with dronedarone, as compared with placebo. Dronedarone also reduced the ventricular rate in atrial fibrillation during recurrences of arrhythmia.

His conclusion avoided the topic of indications of liver dysfunction.

The ATHENA Study

Finally, Sanofi-Aventis set up a trial practically guaranteed to show safety and efficacy. They called it ATHENA, and it got them just what they wanted: FDA approval. The trial was, of course, financed by Sanofi-Aventis. The lead researcher-author, Stefan H. Hohnloser, MD, is neck deep in Big Pharma money. He collects consulting fees from Sanofi-Aventis and many others.

At the time it was published, ATHENA came under serious criticism. TheHeart.org's Steve Stiles quoted the Journal of the American College of Cardiology (JACC):

[L]imitations in the design and execution of the key trial supporting dronedarone's approval, ATHENA, "raise questions about the quality of [its] data" and "cast doubts on their relevance to clinical practice."

As usual, though, that didn't matter to the FDA. The trial claimed good results, which seems to be the only significant issue. Actually reviewing a trial does not appear to be of any concern to them.

ATHENA was a two-year study that claimed to show benefits from Multaq over placebo in reducing death from cardiovascular causes. It also showed an increase in deaths from other causes. There was a 1% improvement in the death rate from all causes, which the study itself did not claim was significant.

Since life extension is the real goal of taking Multaq, one would think that the trial's own admission that there was no significant extension of life would be the end of it. Obviously, that wasn't the case.

Patients were followed for a minimum of 1 year and a maximum of 2.5 years, with a median of 22 months. Those with severe heart disease were not accepted into the trial, no one with any other life-threatening condition was included, and no one with low glomerular filtration rate or low potassium levels was accepted.

4628 patients were enrolled, and the intention-to-treat method was utilized. This means that all patients' results were included as if they'd been present until the end of the trial. The dropout rate was high: 696 (30.2%) of those who took Multaq, and 716 (30.8%) of those on placebo. 12.7% of the Multaq group left because of adverse events. 8.1% of the placebo group left for that reason. About 50% more people who took Multaq than took placebo left the trial because of adverse effects. That alone could account for the entire minimal benefit shown by this trial, and make the results so bad that even Sanofi-Aventis wouldn't have been able to spin them.

When one also considers that the trial showed significantly increased liver risk, which would increase over time, even this trial, which claimed to show benefit, actually documents the opposite. Yet, it was the trial that resulted in the FDA's approval of Multaq.

The Dronedarone Molecule Carries Obvious Risks

The Multaq (dronedarone) molecule is formed from the base of a benzofuran and a benzene molecule. Benzofuran is formed from benzene and furan rings. It is pictured to the left, with benezene circled and labeled in green, and furan circled and labeled in red.

Benzene and furan are both highly poisonous. Benzene is a carcinogen. The presence of these chemicals as the basis of the dronedarone molecule should be treated as potentially dangerous. Of course, the same, or equivalent, can be said for many other drugs. That, though, begs the question: Why are we presuming that these drugs are safe? When they're composed of highly toxic chemicals that have no metabolic function in our bodies, it seems the height of irrationality and recklessness to utilize them as medicines without first testing them thoroughly to assure that we know what degree of harm they produce before we use them as medicines.

There may be a case for treating these chemicals as medicines. However, it is beyond belief that these chemicals unknown to the natural world, and therefore having unknown effects on our bodies, are pushed on us as medicines—usually with little benefit—without knowing their full effects.

Rise and Fall of Each Drug

Over and over, the rise and fall of pharmaceutical drugs follows a similar trajectory:

1. First there's the hype, usually before it's even been tested. This assures that there's plenty of pressure to get the drug approved, whether from doctors or patients doesn't particularly matter.
2. Then, there are tests, which are nearly always badly designed and financed by the drug company that hopes to make a killing on it.
3. After that comes the real trial. Human beings become guinea pigs without knowing it. Over time, the lack of efficacy or the existence of serious adverse effects, or both, become known.
4. After hemming and hawing, excuse-making and even outright lying, the pharmaceutical company drags out the lifespan of the drug to increase profits. Ultimately, the drug is either retired or is removed from the market.

Multaq is in the hemming and hawing, excuse-making stage. Sanofi-Aventis is putting out a warning because liver transplants have been done and patients have died from liver failure. Sanofi-Aventis doesn't acknowledge that there's any cause-and-effect, though. Because of the topsy-turvy system we have, they're able to drag out the period of time profits are made from their poison. Most doctors will continue to prescribe it until it's removed from the market. And people will continue to be harmed.

To acknowledge the reality, I've modified Sanofi-Aventis' logo. Instead of reading "Because health matters", it now says the truth, "Because profits matter".

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