What should I have told the doctor who recently asked me about dronedarone (Multaq)?
“Supposedly, it’s [Multaq] just like Amiodarone, but without the side effects?” he asked.
Gosh…Should I, or shouldn’t I?
I took a big cleansing breath, reminding myself to stay civil, as at least Sanofi-Aventis, the makers of Multaq, sponsor a cycling team. Then I gave him my long answer:
I started with the fact that Multaq barely made it through the approval process. One of the original studies with Multaq (ANDROMEDA), a randomized trial of Multaq in patients with severe heart failure, showed that patients who took the drug were twice as likely to die.
Multaq eventually won approval for use in patients without significant heart failure and mild forms of AF, based on the results of the ATHENA trial—which randomized 4628 patients with non-permanent AF to either standard therapy or standard therapy plus Multaq. The ATHENA investigators didn’t exactly say that Multaq works, rather they claimed that it reduced a composite of hospitalizations and death.
This started the marketing machine in motion, the likes of which I have not ever witnessed. Read more »
*This blog post was originally published at Dr John M*
Toxicity reports are re-emerging in southern California this week after a dozen hospitalizations of kids using teas made from a fragrant flowering plant called Angel’s Trumpet.
A tea made from the plant is used to produce hallucinations, but they can progress to extremely unpleasant experiences. Moreover, Angel’s Trumpet can be deadly, accelerating the heart rate and causing fatal cardiac rhythmic disturbances and bronchoconstriction that can trigger asthma attacks in sensitive individuals. Read more »
*This blog post was originally published at Terra Sigillata*
The Centers for Disease Control (CDC) currently recommends that children 6 month to 18 years old receive an annual flu vaccine. There are two types of flu vaccines used in the US: a live attenuated virus (LAIV) and a trivalent inactivated virus (TIV) vaccine. Both are safe and effective – while efficacy varies from year to year, they are 70-90% effective in healthy adults. Efficacy is young children appears to be slightly less, about 66%.
There remains, however, many sub-questions about the flu vaccines and by the time researchers have thoroughly explored them vaccine technology is likely to have progressed, and therefore any new vaccines will have to be tested all over again.
One of those sub-questions about vaccine safety and efficacy is the net effect of the flu vaccine in children with asthma. Some have raised concerns that the vaccine may exacerbate asthma, a 1-2% increased wheezing and 3% increased hospitalizations have been reported, although so far the bulk of the data suggests that both types of flu vaccines are safe in children with asthma. There is evidence to suggest that the LAIV may be superior to the TIV in children, particularly with asthma.
A new study, presented but not published, further explores the safety and efficacy of the TIV in children. Study author, Avni Joshi, M.D., of the Mayo Clinic, reports:
“The concerns that vaccination maybe associated with asthma exacerbations have been disproved with multiple studies in the past, but the vaccine’s effectiveness has not been well-established. This study was aimed at evaluating the effectiveness of the TIV in children overall, as well as the children with asthma, to prevent influenza-related hospitalization.”
The study is a retrospective study of 263 children who presented to the Mayo clinic with laboratory confirmed influenza. They found that children who had recieved the TIV vaccine had a 3 times greater risk of hospitalization than those who were not vaccinated. These results raise concerns about the safety and effectiveness of the TIV in children with asthma.
Dr. Joshi concludes:
“While these findings do raise questions about the efficacy of the vaccine, they do not in fact implicate it as a cause of hospitalizations. More studies are needed to assess not only the immunogenicity, but also the efficacy of different influenza vaccines in asthmatic subjects.”
That may seem like a curious conclusion given the results of this study, but it is accurate. The key to understanding the implications of this study is that it is retrospective. That means it looks at children who have the flu and then looks back to see who was vaccinated and who wasn’t. This in turn means that children were not randomized to either be vaccinated or not, and this opens the door to any number of variables that cannot be controlled for in the study.
The authors did look as obvious factors, such as severity of asthma and insurance status, and found that they did not correlate with risk of being hospitalized. But what other factors might there be? The flu vaccine is optional, which means that parents decide whether or not to vaccinate their children, perhaps with advice from their pediatrician. It is likely that sicker or more frail children are more likely to get vaccinated. It is also likely that children who had a bad reaction to the flu in the past are more likely to get vaccinated. The flu vaccine is recommended especially for those who are at high risk for complications if they get the flu.
Therefore while this study raises important questions, it is not designed to answer them definitively. A prospective trial is required for that, and that is what Joshi means by “more studies are needed.” In general, retrospective studies are useful to find correlations and generate hypothesis, but are not capable of determining causation – there are simply too many variables that are not controlled for.
As expected, the anti-vaccinationists have already jumped on this study and misinterpreted its significance. They did not recognize its retrospective nature nor put it into the context of existing research on the safety and efficacy of the flu vaccines.
Clinical trials are complex, and there are many types that each have their own strengths and weaknesses. Often, many independent lines of basic science and clinical evidence need to be brought together to form a reliable conclusion about a specific intervention. That is the essence of science-based medicine. Individual studies typically only provide a tiny slice of information, but are often presented to the public as if they are definitive. This creates a constant background noise of misinformation about medical questions.
It also provides a rich source of data from which to cherry pick, allowing proponents to support almost any notion by shopping from the vast store of often conflicting medical research. This reinforces the need to look thoroughly at the totality of scientific evidence on any claim or question.
When that is done on the question of the flu vaccines, it is clear that both types of vaccines are safe and effective. However, there is also much room for improvement in the vaccine technology itself, as well as evidence-based recommendations for who, exactly, should get which type of vaccine.
This current study adds incrementally to our knowledge on this question, and suggests questions for future research. It is not the kind of evidence, however, that should lead to changes in the current recommendations.
*This blog post was originally published at Science-Based Medicine*