University of Michigan professor addresses controversy with cholesterol-lowering statins
If you've ever been diagnosed with cardiovascular disease, chances are your doctor also discussed statin drugs with you.
But chances are, you might have been prescribed statins if you were at increased risk for but did not yet have cardiovascular disease.
According to a new analysis of data from previously published studies, there is little evidence that the wide use of statins primarily for prevention reduces risk of death. The analysis was published Monday in the Archives of Internal Medicine.
Statins are a class of drugs used to help lower a person's cholesterol levels to reduce a person's chance of heart attack or stroke. The drug Lipitor, which was developed by Pfizer Inc. when it was still located in Ann Arbor, is a statin.
Statins have become one of the most widely prescribed medications for the prevention of cardiovascular disease, but have become greatly controversial in their use, says Lee Green, a University of Michigan professor in the Department of Family Medicine.
Lee Green, University of Michigan professor in the Department of Family Medicine.
"For secondary prevention patients, or people who have coronary heart disease, there is no controversy. Statins have been shown to be an effective treatment," Green said. "The question raised is about the use of statins in someone who has not been diagnosed and whether they’re worth it.
Green teaches a course for new physicians with the intent to teach them how to evaluate the constant stream of new published studies, and other sources of information, they will use to inform their practice of medicine in the future.
In an editorial also appearing in the Archives of Internal Medicine, Green questioned the value of previously published studies touting the value of statins, pointing to conflicts of interest in the funding of the research.
He answered some questions this week about his thoughts on the statin controversy.
Q: You mention in your editorial there is a lot at stake for both payers (insurance companies) and industry (drug companies). What about patients?
A: "There’s a lot at stake for patients. For example, there are a lot of people who have no symptoms and don’t have identified disease who might be taking a medication for many years. Not to mention that could mean a lot of money for the patient … This is asking a lot of people to take a lot of pills with an unknown benefit to only certain people while exposing every patient to potential side effects."
Q: What is the most effective primary prevention behavior in coronary disease if it’s not taking statins? Do we know?
A: "We absolutely know. It’s movement. Exercise. Get off that sofa and put down those pork rinds. If you really look at data among folks who are overweight, it’s among those who are sedentary overweight who are most at risk for coronary heart disease.”
Q: You teach future doctors in medical decision making and practice guidelines. What do you think of current prescribing practices?
A: “It’s all over the map now. Some physicians are conservative, some are aggressive … Right now, statins are both over and underprescribed. Frankly a lot of the overprescribing can be related back to marketing by the pharmaceutical industry."
Q: Your editorial really raises questions about the nature of studies conducted with funding from industry. Why is that important?
A: "It's publication bias," Green said pointing to studies which show links between funding sources and the outcomes of drug studies. In the editorial, he wrote, "Doubtless both sponsor and investigative team believe that they made their design decisions for the right reasons, but social psychology research provides abundant evidence that we human beings both respond strongly to self-interest incentives and firmly believe we do not."
Q: The University of Michigan medical school recently became the first to say it will no longer accept funding from drug or device makers for its continuing education classes for physicians, it was reported in the New York Times. What do you think about this decision? (Green is serving on the conflict of interest review committee at the medical school.)
A: "I'm proud to say U-M has been a real leader in removing conflicts of interest in education … Continuing medical education (for physicians) has been a major target of the pharmaceutical industry. If we really want to do the best for our patients, we need to get that thumb off the scales. We have to stop pretending money doesn't buy our judgment."
Tina Reed covers health and the environment for AnnArbor.com. You can reach her at tinareed@annarbor.com, call her at 734-623-2535 or find her on Twitter @TreedinAA.
Comments
Rork Kuick
Thu, Jul 8, 2010 : 8:40 a.m.
Maybe I can clarify two small things. I think the public should fund lots of research, but we don't want to fund all of it, and we should be skeptical even of publicly funded research. There are lots of ways to fool yourself, and it's hard to not want your great new thing to work, since it can impact future public funding. Also, I don't want to demand that all trials analyze only real endpoints with 30 year follow-up, since that means it'll take forever to widely implement promising new cancer treatments for example - that is a very difficult area. It will take nearly forever to see if the new treatment really works better whether it's widely implemented or not - there's nothing for that - and we just face the terribly difficult decision of whether to implement on imperfect knowledge in the meantime. Imagine treatments for childhood cancers for example, where treatment A "cures" slightly more kids than B, but may give more second cancers later (not sure). Even with perfect knowledge it could be an agonizing trade-off.
Rork Kuick
Thu, Jul 8, 2010 : 8:02 a.m.
David I agree with everything you said, and I could add lots more. I wildly advocate "intention to treat" analysis of trials. I wildly advocate real endpoints in place of surrogate endpoints, but pointed out that that can be almost impossible for less common diseases (like breast cancer, even though the studies involve thousands of women - for heart attack it's more feasible cause it's a bit more common). You claim I'm failing to understand, but I did not see you advocating that pharma not be able to fund research at public institutions. Who did you want to conduct the trials? Who did you want to pay for them? I do not expect better behavior from pharma than from big oil or military concerns. We need watchdogs and more rules for this stuff. My drift goes to this: I do not want anger at big drug companies to make people start to think that they'd be better off quitting their doctor and going to a naturopath, or homeopath, or chiropractors or acupuncturists treating asthma, or energy-medicine quacks, or the advice of actresses, of which there are a shocking number around here, and where the error and financial incentives are without end. For evidence-based medicine, I think things are actually improving lately.
Lady Audrey
Wed, Jul 7, 2010 : 5:36 p.m.
Rork: it is true that all industry is driven by profits but there is a special expectation of those entrusted with human health, that their mission not be solely profits and that the protection of their consumers be at the forefront. I applaud independent scientists like Dr. Green who take the time to look at the true facts and then publish evidence that refutes pharmaceutical marketing, or at least, attempts to do so. It is difficult to be heard over the sound of all that money counting.
David Staup
Wed, Jul 7, 2010 : 11:07 a.m.
Rork your responce shows such a lack of understanding of what's actually going on it's almost comical..I'd actually be satisfied if pharma would only honestly gather and present thier data instead of designing thier trials to give the answer they want and presenting the results in such a way as to mask the truth, see the following: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079612/ now to the way the trials are performed to hide adverse effects: From an article in Discover Magazine Wonder Drugs that can Kill! http://discovermagazine.com/2008/jul/20-wonder-drugs-that-can-kill Golomb says one reason many doctors overlook risks and believe statins to be safe is that most controlled studies of statins wind up excluding people who originally begin to participate in a study but stop taking the drug because they experience problems from it; these test participants are then dropped from the study as noncompliant. Confusion arises, Golomb says, because the absence of evidence that statins cause harmhaving excluded those who would have permitted detection of harmis interpreted wrongly as evidence of absence of harm. And the treatment is generalized to a larger population with a very different risk-to-benefit profile. Another problem with statin studies, according to Abramson, is that many do not measure clinically and critically important outcomes like heart attacks, serious adverse events, or all-cause mortality. Instead they measure surrogate markersoutcomes that are associated with a risk of diseasebut not a bad outcome itself. In the case of statins, the surrogate marker most commonly used is cholesterol levels. If a drug reduces cholesterol, it is said to be effective. But lowering cholesterol doesnt necessarily mean a drug will reduce the bad outcomes people are worried aboutsuch as death or heart attack. This was the issue in last winters congressional investigation into the nonstatin cholesterol-lowering drug ezetimibe, sold as Zetia and contained in Vytorin. Hearings in January revealed that the release of negative results of a clinical trial of ezetimibe had been delayed. The drug, while lowering cholesterol effectively, failed to slow the progression of carotid artery plaque. While manufacturers Merck and Schering-Plough delayed the negative studys release for more than 18 months, ezetimibe had turned into a blockbuster drug, even though it had never been shown to reduce heart attacks or deaths. You can lower cholesterol levels with a drug, yet provide no health benefits whatsoever, Abramson says. And dying with a corrected cholesterol level is not a successful outcome in my book. Suddenly Abramson, who had taken many hits for his critiques of cholesterol-lowering drugs, was joined by physicians calling for more openness in research and more careful examination of the evidence before drugs are put on the market. a link to a study on the adverse effects of statin drugs: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849981/ the author of the above study is currently involved in a study to determine the percent of statin users that experience statin damage and the.5% claimed by pharma studies is actually over 10% and may be as high as 20%! and finally ask yourself this: How difficult would it have been to follow up on the participants of the original trials??? and shouldn't that be required of all clinical trials! finally ask yourself this: in 2005 the reporting requirements for drug trials were changed after the vioxx scandle. all statin trials since then have failed except for JUPITOR and it is under fire for various reasons... http://www.jstage.jst.go.jp/article/jln/19/1/65/_pdf
Rork Kuick
Wed, Jul 7, 2010 : 7:12 a.m.
Since every industry is driven by profits, I don't see how that makes pharma particularly broken. Good evidence is not easy or cheap to come by. For all-cause mortality endpoints, you may need huge trials - we haven't even shown mammography improves all-cause mortality for example. Finally, in clinical trials, it almost has to be publicly done research, unless you'd prefer to have the trials conducted in the basements of the pharmaceutical companies, and just trust their results.
Lady Audrey
Tue, Jul 6, 2010 : 10:49 a.m.
I applaud Susan for reminding everyone that Parke Davis/Warner Lambert scientists, thrown to the curb by Pfizer, invented Lipitor. Pfizer invents very little. It was a marketing partner for Warner Lambert who didn't have the giant machine for promoting its life-saving drug. Of course, now that Pfizer owns it solely, they can over-market to their heart's content. (Pun intended) Just look at the marketing fraud in the Bextra case where Pfizer was fined $2.3 B http://news.bbc.co.uk/2/hi/business/8234533.stm The pharma industry is "broken" driven only by profits.
AlphaAlpha
Sun, Jul 4, 2010 : 12:12 p.m.
Good point, well taken. Perhaps it's that there is no overt refutation by docs of the perception that taking meds will alleviate the need for good habits is wrong. Actually, too many people do not get the basic advice you mentioned. Some docs assume other docs dispensed it; some docs are 'too busy'; some just don't care. Common sense is uncommon. You are correct, people make their own choices. But it remains that the docs have a financial incentive for you to need their help, instead of an incentive to keep you healthy. And, very regrettably, most docs are very ignorant of nutrition. Almost criminally so. The benefits of good nutrition are profound.
AlphaAlpha
Sun, Jul 4, 2010 : 12:39 a.m.
Almost forgot - Trans fats (partially hydrogenated anything) cause CVD. Harvard Medical has done much research proving trans fat consumption is associated with a substantially increased risk of CVD, as well as sudden fatal first time heart attacks; about 20,000 people each year are lost due to the intake of partially hydrogenated fats, just in terms of CVD. Way more people are lost from bad habits than saved with statins. It is unfortunate that many consider it more convenient to take a pill, even an expensive pill, than it to eat right and exercise. If our medical business process financially rewarded doctors for keeping their customers healthy, instead of as now, where doctors earn money when customers need procedures and pharmaceuticals, doctors would dispense far more common sense preventive advice like "eat right and exercise".
Peregrine
Sat, Jul 3, 2010 : 9:03 p.m.
Hey Everyone, Dr. Green is being very careful as to what he says. Quoting the article, "But chances are, you might have been prescribed statins if you were at increased risk for but did not yet have cardiovascular disease.... According to a new analysis of data from previously published studies, there is little evidence that the wide use of statins primarily for prevention reduces risk of death." And Dr. Green is quoted as saying, "For secondary prevention patients, or people who have coronary heart disease, there is no controversy. Statins have been shown to be an effective treatment," and later, "Right now, statins are both over and underprescribed [sic]." So, DougEFresh, can you cite the evidence that the wide use of oatmeal primarily for prevention reduces risk of death from cardiovascular disease? Because that's the standard Dr. Green is using to evaluate statins. And I don't see why you can hold statins to one standard and anything else, such as oatmeal, to a lower standard.
DougEFresh
Sat, Jul 3, 2010 : 8:19 p.m.
Oatmeal. Oatmeal is proven to help the heart, but docs often rush to prescribe side-effects-causing statins before telling patients to eat oatmeal everyday. U of M has a looooong way to go to wean itself off the pharma tit. Of course, it's the whole industry complex and medical mentality. My personal experience is that UM ONLY researches pharma solutions for medical problems.
AlphaAlpha
Sat, Jul 3, 2010 : 7:01 p.m.
"Does UofM also plan on limiting drug company funding of research?" Great question. Not only in research, but in the hospital business as well? Likely answer: No. Why? To quote Mr. Green: "We have to stop pretending money doesn't buy our judgment". Big Pharma (the direct descendants of the 1800s traveling snake oil vendors) affects better medical judgment, repeatedly, every day. Virtually every doctor, every school, every hospital: judgment being bought on a massive scale. With your money. You the customer. "We have to stop pretending money doesn't buy our judgment." Mr. Green and the UM are to be commended for this first small step toward independence from the pharmonopoly. The other hugely helpful way to improve CV health: ingest essential fatty acids. Exercise and EFAs are far more effective and less costly than statins. But guess what? There is no patenting food and exercise; this explains in large part why most pharma influenced docs remain clueless.
David Staup
Sat, Jul 3, 2010 : 4:43 p.m.
as a victim of the adverse affects of statin drugs who was ultimately disabled by those affects I applaud UofM for their decision heartily. The use of statins for primary prevention and secondary prevention outside of a narrow age range (~45 to 60 yrs) is criminal in my opinion and studies with proper end points, such as all cause mortality, should be used to judge the verasity of drug company claims. Does UofM also plan on limiting drug company funding of research?
Peregrine
Sat, Jul 3, 2010 : 12:51 p.m.
I too am proud that UofM has moved against drug and medical device manufacturers having inordinate influence on physician continuing education. If you could follow up with Dr. Green, I'd like to know whether his research has given him a perspective on the apparent anti-inflammatory properties of statins and whether they might have an alternate health benefit to those taking them.
BobbyJohn
Sat, Jul 3, 2010 : 12:40 p.m.
Congrats to UM Hospital for putting their patients first this time. Keep it up!
Susan Montgomery
Sat, Jul 3, 2010 : 7:56 a.m.
Correction - Lipitor was invented by Dr. Bruce Roth of Warner-Lambert/Parke-Davis, not Pfizer. Pfizer bought Warner-Lambert/Parke-Davis years after that in a hostile take-over, in part to get the profits from Lipitor. Let's not give Pfizer credit for the invention...