Here’s a cardiac research story so confusing that the average dull-witted heart attack survivor like me can barely keep up with the plot. So let’s try telling the tale in pared-down plain English to see if we can figure out how two well-respected “experts” can have such viciously opposing interpretations of the same research, and what factors might just be at work to influence those opinions – financial and otherwise.
But before even looking at the story’s details, let’s do what everybody should do before evaluating any study results: fast-forward to the end of the research report until you find the teeny tiny fine print revealing researchers’ conflict of interest disclosures. And it turns out that each of the opposing researchers in this story has plenty of reason to trash the other’s interpretation.
The original researcher was Dr. Paul Ridker, a well-respected physician from Boston and lead author of the now-famous 2008 JUPITER* trial, studying the effects of an anti-cholesterol statin drug called Crestor. The drug emerged from this study as the darling of the cardiology world, credited by Ridker’s team with a 44% potential reduction in cardiovascular events thanks to its revolutionary ability to not only lower LDL (bad) cholesterol, but also to reduce levels of a blood marker for inflammation called C-Reactive Protein (CRP).
Ridker’s conflict of interest disclosure: his JUPITER research was actually funded by AstraZeneca, the very drug company that makes Crestor. He’s also received previous grants and consulting fees from the same company. In fact, nine of the 14 authors of the JUPITER study have financial ties to AstraZeneca. He also happens to hold the legal patent on CRP blood-testing technology that stands to explode in sales if his JUPITER study’s recommendations are accepted by cardiologists worldwide. So he has much to gain with the publication and acceptance of his research.
But this month, France’s Dr. Michel de Lorgeril, another equally well-respected physician, along with researchers from several countries, took a much closer look at Ridker’s JUPITER results. His team published their interpretations in the Annals of Internal Medicine this month, concluding that the JUPITER trial is “flawed” on many levels, biased by commercial interests, and its findings have actually been exaggerated to favour the drug, not the facts. One critic branded Lorgeril’s report as “troubling” and “offensive.”
De Lorgeril’s conflict of interest disclosure: he and one of his study co-authors are members of a group called The International Network of Cholesterol Skeptics (THINCS), who oppose the belief that animal fat and high cholesterol play a role in the causation of cardiovascular disease. He too has much to gain with the publication and acceptance of his research.
So which physician is correct, and which is producing results for personal gain or ulterior motives?
I’ve heard cardiologists joke that statins like Crestor are such miracle drugs that we should be putting statins into our drinking water. At least, I think they were joking. JUPITER reinforces the indisputable power of statins in maintaining cardiovascular health, and of course particularly the power of the brand-name statin, Crestor.
But a growing number of JUPITER skeptics are beginning to dispute the study’s findings. Some say that the absolute reduction of cardiac events among the healthy patients studied was actually low, and would come at the considerable cost for years of treatment with Crestor.
Others claim that cutting the research short less than two years into the trials unfairly skewed JUPITER results in Crestor’s favour. Dr. Gordon Guvatt, an epidemiologist, biostatistician and professor of medicine at McMaster University offers a particularly compelling argument disputing the dramatic cardiac benefits reported in JUPITER. Instead, he says the trials showed only “tiny absolute effects” and vastly “over-estimated relative effects” specifically because of the decision to stop early trials. Another alarm about cutting research trial short comes from the Healthcare Channel’s Dr. Steve Greer in this MarketWatch interview.
And consider this joint statement published in the U.K. medical journal Lancet (March 27, 2010) from Drs. David Wald and Jonathan Bestwick:
“The available evidence shows that CRP measurement has no practical value in the prediction or management of coronary heart disease or stroke.”
Or for another alarming perspective from The New England Journal of Medicine (November 2009) on the pervasive practice of “selective outcome reporting” in Big Pharma-sponsored medical research, read Warning: Clinical Trials Funded By Drug Companies May Appear More Truthful Than They Actually Are.
In addition to the de Lorgeril paper, three other articles question some of the JUPITER findings. These include:
- a “special article” on JUPITER by Drs. Sanjay Kaul, Ryan Morrissey and George Diamond (Cedars-Sinai Medical Center, Los Angeles)
- a meta-analysis of statin trials that suggests there might not be a mortality benefit of these drugs in primary prevention by a group led by Dr. Kausik Ray (University of Cambridge, UK)
- a critical editorial by Dr. Lee Green (University of Michigan Medical School)
Read more about this controversy. And if you still need to be convinced that it’s an inherently unsound idea for drug studies to be funded by the very drug companies who stand to gain financially if the studies are positive, read When You Use Bad Science To Sell Drugs.
UPDATE: A Johns Hopkins University Medical School study presented results that also challenged the JUPITER findings at the American Heart Association’s November 2010 scientific meetings. Researchers reported that people who are otherwise healthy and have no significant coronary artery calcification should focus on aggressive lifestyle improvements instead of early initiation of statin medications, according to cardiologist and study lead investigator Dr. Michael Blaha, M.D., M.P.H.
“It certainly is not the case that all adults should be taking statins to prevent heart attack and stroke. High levels of C-reactive protein in the blood offered no predictive value after established risk factors are taken into account, including age, gender, ethnicity, hypertension, blood cholesterol levels, obesity, diabetes, smoking and a family history of heart disease.”
* The JUPITER trials: first released in 2008, involved 17,802 healthy men and women with normal LDL-cholesterol levels but elevated CRP levels assigned to take a drug called rosuvastatin 20 mg (Crestor, made by AstraZeneca) 20 mg or a placebo pill . JUPITER was stopped after 1.9 years of follow-up. Research results reported that Rosuvastatin significantly reduced non-fatal heart attacks and strokes, hospitalization for unstable angina, revascularization procedures like bypass surgery or cardiac catheterization, and confirmed death from cardiovascular causes compared with placebo. There was a 55% reduction in non-fatal heart attack, a 48% reduction in the risk of non-fatal stroke, and a 47% reduction in the risk of heart attack/stroke/cardiovascular death.
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“….He has much to gain with the publication and acceptance of his research…”
I think you’ve hit the nail on the head. Just look at the “EXPERT” who has the MOST to gain financially – and that’s the one whose EXPERTISE is least likely to be trusted. Doctors will deny this of course but come on now – – – in what other industry is this kind of conflict of interest tolerated?
Great site. A lot of useful information here on the importance of reading all the FINE PRINT in medical research reporting. I’m forwarding this to some friends.
This student has a very narrow view of academic research life. First, to assume that a student’s skills are as valuable as a research technician’s, who has been trained extensively in the techniques used in the lab and has experience is a fallacy.
It is interesting and informative to read this. you are right, this is a confusing one.
Thanks for the informative review. I also found it interesting how they wrote off the increased diabetes risk in the arm taking rosuvastatin as unexplainable, therefore, not important.
Yes, me too. The JUPITER authors described this increased risk of incident diabetes (9%!) as “statistically significant” yet “slight”. Why is this? Dr. David Preiss at the University of Glasgow muses that the risk may be the result of an off-target effect of treatment, or even an indirect result, where “those experiencing muscle pain or weakness caused by statins are less likely to exercise, resulting in more diabetes.” More on this at http://www.theheart.org/article/1047959.do
Also – thanks, docsquawk, for letting me know about that broken link!
“De Lorgeril’s conflict of interest disclosure: he and one of his study co-authors are members of a group called The International Network of Cholesterol Skeptics (THINCS), who oppose the belief that animal fat and high cholesterol play a role in the causation of cardiovascular disease. He too has much to gain with the publication and acceptance of his research.”
I fail to see what he and others (who seem not to write at all or often at THINCS) have to gain. This is a poor comparison to Ridker’s financial interests.
That is precisely the point. See Dixon May’s comment above for an explanation.
Yes, but when you write “De Lorgeril’s conflict of interest disclosure…..He too has much to gain with the publication and acceptance of his research.”,
you seem to support those who :
– dismiss him on this ground
– without trying to reply to the evidence he brings.
That is not fair.
This is strange because it is at odds with the general tone of your paper.
Or maybe I missed something ?
Yes, maybe you have missed something. Again, see Dixon May’s comment above: “Just look at the “EXPERT” who has the MOST to gain financially – and that’s the one whose EXPERTISE is least likely to be trusted.” Dr. de Lorgeril clearly appears to be least likely to gain financially here, right?
Yes Carolyn, I indeed had seen this comment but sincerely, when I read YOUR PAPER, I understand you suggest De Lorgeril has a lot to gain too. I’m glad you agree with Dixon May :p)
I just discovered this site. I have been obsessed with this subject since I was a Crestor victim several years ago. After taking a low dose of this drug for several months, I developed a laundry list of symptoms. Having not been warned about side effects, I concluded that old age was quickly setting in. Eventually, I found some websites devoted to the negative side effects of statins and realized the truth, I was being poisoned.
I went off the medication and quickly recuperated. This experience left me quite frustrated and angry. The FDA and the medical profession do not take our very real complaints seriously. Both my old doctor and my new one stated that they would not report my complaints to the FDA because they were not “serious enough”.
Must a patient wind up in the hospital or dead before anyone pays attention? The real problems we experience from drugs are anecdotal, while Big Pharma statistics are the gold standard. The fact that the FDA now lists memory problems as a possible side effect of statin drugs is because of patient complaints. How many patients actually complain? Surely those they hear from are just the tip of the iceberg.
It is not outside the realm of possibility that dietary cholesterol may not be the great satan. Gluttony, lack of exercise and heredity all play a role. No one lives forever. Can Big Pharma extend our lives and better the quality?
Ultimately each one of us has to make our own decisions about our health. What do we eat, how much do we exercise, do we take drugs to lower our cholesterol or supposedly to strengthen our bones. We must educate ourselves and be armed with our own research to better decide when and if we want to add big pharma into the equation. I for one, take their biased conclusions, with a healthy dose of skepticism and a grain of salt.
Thank you for this most informative website.
Thanks for sharing your perspective, Marjorie. It’s a good reminder for patients to report their own significant drug side effects (here’s the FDA MedWatch reporting info). And unless you are already a heart patient at high risk for future cardiac events, there is considerable evidence that women at low risk for cardiovascular disease should not take statins merely for the purposes of managing (intermediate endpoint) cholesterol numbers.
I appreciate most of your paper, but then you wrote : “He too [Dr Michel de Lorgeril] has much to gain with the publication and acceptance of his research.”
MUCH to gain ???
What are you talking about ?
I know his work and researches very well.
Note that I am just an European patient who had 3 acute myocardial infarctions under statins and is now PERMANENTLY crippled by an irreversible myopathy caused by these drugs.
Do you realize that Dr Lorgeril is a researcher working in a public national research center (CNRS) ?
Each month he earns the same reasonable salary, with or without “publication and acceptance of his research” !
And he is published (try a search under his name on pubmed) and his Lyon Diet Study is respected in the whole wide world !
This argument (mainly started by the like of Cardiobrief & Marilyn Mann) is TOTALLY unfair. It is a LIE and a RIDICULOUS lie for those who know.
Dr Lorgeril doesn’t try to sell us any drugs or complements, he repeatedly explains that cardiovascular diseases are the result of our way of life, that if we want to protect ourselves against these diseases (even in secondary prevention) we have to eat differently (Mediterranean diet), to have more physical activities, etc.
Yes, he sells a few books (in french) about this and the cholesterol/statin scam. Very serious books, with a scientific analysis of the studies, nothing easy or very fun to read.
How could this make him earn billions of $ every year like the CRESTOR industry Ridker is working for ?
I don’t understand !
And I didn’t miss something. Dixon May’s comment is NOT part of your paper.
P.S.: Excuse my poor English, I am Belgian and French is my first language.
Thanks so much for taking the time to respond, Jacques. Please reread this post; you’ll see that I agree with your perspective. “Much to gain” includes both financial and non-financial (reputation, credibility, etc) potential benefits of holding a specific position. Many physicians who share Dr. de Lorgeril’s views questioning the growing popularity of statins – particularly as primary prevention in low-risk patients – do not of course stand to gain financially from their association with Big Pharma (as statin proponents like Ridker do), but are well-known and respected in medical circles and often cited specifically because of their anti-statin cautions (e.g. Drs. Rita Redberg, Malcolm Kendricks, Eric Topol, John Mandrola, Barbara Roberts, etc). This increased public and professional profile is a “gain”. Not a financial gain, but not all gains mean money.
PS Your English is outstanding!
This discussion has taken on the tone of a witch hunt. If you’re one of those vocal critics who don’t believe the results or conclusions of the JUPITER study then don’t take statins. If you do take stains and the risk/benefit calculation is not in your favor then stop taking them. If you don’t like the fact that large clinical trials such as JUPITER are funded by the drug companies then consent to having your taxes pay for expensive Phase III clinical trials (though it takes more than money to do it properly); but don’t assume that results from agency-conducted trials will somehow be devoid of differing interpretations from reasonable people.
The bottom line is that I’m glad that statins exist as approved drugs. I hope I never need them, will continue to diet (Mediterranean) and exercise, but I’m glad statins exist as another option that may help further mitigate my risk going forward.
I suppose you’re right. The tone of this discussion could well be considered a “witch hunt” in much the same way many public health officials reacted during the 1960s when Big Tobacco openly paid physicians to testify that smoking was not associated with any known health issues. Today in hindsight, we are shocked that such “scientists” were considered even remotely credible given their clear financial conflicts of interests at the time. The relevant question is of course: how credible is the ‘science’ bought and paid for by industry when its sole purpose is to boost sales?
And there’s already considerable independent non-industry-funded research (Ray et al 2010, Cochrane 2011, Women & Health Protection 2007) describing the evidence promoting statins for primary prevention in low-risk people and related all-cause mortality reduction claims as “an extreme and exaggerated finding”. And as Dr. Eric Topol warned in Forbes recently: “The diabetes risk (of taking statins) does not just show up in JUPITER – it is consistent in every trial of high potency statins.”