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, apparently 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 acceptedby 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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