A bad week for statins

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Despite the fact that statin drugs are the best-selling medications in history, accounting for some $40 billion plus in sales world wide last year, they had a very bad week this past week. And it looks like their scrutiny is going to pick up a little.

The Vytorin trial that finally came to light late last week kicked off the cascade of bad news. It appears that the combination of a statin and Zetia, despite lowering cholesterol levels by 40 percent more than a statin, was no more effective than the statin alone in preventing problems. Which would lead anyone with critical thinking skills to wonder about the hypothesis that LDL-cholesterol is really a problem.

The next day the New York Times, in an article that wasn’t all that anti-statin, started thusly:

For decades, the theory that lowering cholesterol is always beneficial has been a core principle of cardiology. It has been accepted by doctors and used by drug makers to win quick approval for new medicines to reduce cholesterol.

But now some prominent cardiologists say the results of two recent clinical trials have raised serious questions about that theory — and the value of two widely used cholesterol-lowering medicines, Zetia and its sister drug, Vytorin. Other new cholesterol-fighting drugs, including one that Merck hopes to begin selling this year, may also require closer scrutiny, they say.

Dr. Steven E. Nissen weighed in with his interview with Katie Couric on CBS that I posted earlier.

And the Wall Street Journal in it’s Health Blog anticipated a slew of lawsuits against the makers of Vytorin and maybe other statins to follow.

But the big daddy of them all has yet to hit the newsstands but has already been blasted over the internet. The next issue of Business Week, due to hit the stands next Monday, has been up online for the past few days, and it contains several articles, including the cover article, that are devastating for the makers of statin drugs.

The cover article titled Do Cholesterol Drugs Do Any Good starts right off in lock step with what I wrote in my Queen Mother of all statin posts a year or so ago. The Business Week piece starts with an interview with James M. Wright, a professor at the University of British Columbia and the director of the Canadian government-funded Therapeutics Initiative, an agency that analyzes drug data to see how well they actually work. Dr. Wright had one of his patients – Martin Winn – on a statin for a mildly elevated cholesterol level when the light bulb flashed on.

Wright saw, the drugs can be life-saving in patients who already have suffered heart attacks, somewhat reducing the chances of a recurrence that could lead to an early death. But Wright had a surprise when he looked at the data for the majority of patients, like Winn, who don’t have heart disease. He found no benefit in people over the age of 65, no matter how much their cholesterol declines, and no benefit in women of any age. He did see a small reduction in the number of heart attacks for middle-aged men taking statins in clinical trials. But even for these men, there was no overall reduction in total deaths or illnesses requiring hospitalization—despite big reductions in “bad” cholesterol. “Most people are taking something with no chance of benefit and a risk of harm,” says Wright. Based on the evidence, and the fact that Winn didn’t actually have angina, Wright changed his mind about treating him with statins—and Winn, too, was persuaded. “Because there’s no apparent benefit,” he says, “I don’t take them anymore.”

As I reported in my post the only evidence that statins produce any decrease in all-cause mortality is in men under the age of 65 who have established heart disease. For women of all ages with and without heart disease and for men of all ages without heart disease, these drugs don’t bring about a decrease in all-cause mortality.

And in that small subset of people for whom they do work – men under the age or 65 with a history of heart disease (not a history of high cholesterol, but a documented history of having experienced a heart attack), the evidence is that they don’t work all that well.

What do you mean they don’t work all that well? Robert Jarvik tells us in the ubiquitous Lipitor ads that the drug reduces the risk of heart disease by 36 percent in these people.

The dramatic 36% figure has an asterisk. Read the smaller type. It says: “That means in a large clinical study, 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor.”

Now do some simple math. The numbers in that sentence mean that for every 100 people in the trial, which lasted 3 1/3 years, three people on placebos and two people on Lipitor had heart attacks. The difference credited to the drug? One fewer heart attack per 100 people. So to spare one person a heart attack, 100 people had to take Lipitor for more than three years. The other 99 got no measurable benefit. Or to put it in terms of a little-known but useful statistic, the number needed to treat (or NNT) for one person to benefit is 100.

Compare that with, say, today’s standard antibiotic therapy to eradicate ulcer-causing H. pylori stomach bacteria. The NNT is 1.1. Give the drugs to 11 people, and 10 will be cured.

A low NNT is the sort of effective response many patients expect from the drugs they take. When Wright and others explain to patients without prior heart disease that only 1 in 100 is likely to benefit from taking statins for years, most are astonished. Many, like Winn, choose to opt out.

Plus, there are reasons to believe the overall benefit for many patients is even less than what the NNT score of 100 suggests. That NNT was determined in an industry-sponsored trial using carefully selected patients with multiple risk factors, which include high blood pressure or smoking. In contrast, the only large clinical trial funded by the government, rather than companies, found no statistically significant benefit at all. And because clinical trials themselves suffer from potential biases, results claiming small benefits are always uncertain, says Dr. Nortin M. Hadler, professor of medicine at the University of North Carolina at Chapel Hill and a longtime drug industry critic. “Anything over an NNT of 50 is worse than a lottery ticket; there may be no winners,” he argues. Several recent scientific papers peg the NNT for statins at 250 and up for lower-risk patients, even if they take it for five years or more. “What if you put 250 people in a room and told them they would each pay $1,000 a year for a drug they would have to take every day, that many would get diarrhea and muscle pain, and that 249 would have no benefit? And that they could do just as well by exercising? How many would take that?” asks drug industry critic Dr. Jerome R. Hoffman, professor of clinical medicine at the University of California at Los Angeles.

So even those for whom the statin drugs do show some benefit, that benefit just isn’t all that much in the great scheme of things. And if this tiny, tiny benefit is all that is shown in those for whom the drugs are beneficial, why in God’s name would anyone not in this group even think about taking these drugs? Yet they are prescribed by the millions for just those people. Young people, old people, people who have never had documented heart disease, people whose only problem is a mildly elevated cholesterol level are being browbeaten by their physicians to to on these drugs that are not particularly benign. And with no evidence to prove that the drugs do anything at all to help. It is shameless.

This excellent article should be read in its entirety by anyone contemplating a statin drug. And the two accompanying articles should be read as well. One discusses the many side effects of statins that all too many prescribing physicians want to pretend don’t exist.

In clinical trials of statins, side effects were relatively rare. But many doctors believe they are more common in the real world, afflicting perhaps as many as 15% of patients. After muscle aches, prominently mentioned on Lipitor’s label, common complaints include cognitive problems ranging from mild confusion to loss of memory. Former astronaut and retired family doctor Duane Graveline says that he “descended into the black pit of amnesia” both times he was put on Lipitor, prompting him to write a book and set up a Web site on statins’ side effects.

The other gives the lie to the idea that statins are protective against Alzheimer’s disease.

The sad, sad part of this story as far as I’m concerned is that it has taken the business press instead of the medical press to expose the statin story. Why? The article says it all.

The NCEP’s 2004 guideline update garnered headlines by recommending lower targets for bad cholesterol, which would put more Americans on the drugs. But there was also a heated controversy in the medical community over the fact that 8 of the 9 experts on the panel had financial ties to industry. “The guideline process went awry,” says Michigan State’s Barry. He and 34 other experts sent a petition of protest to the National Institutes of Health, saying the evidence was weak and the panel members were biased by their ties to companies.

As I wrote: sad, sad, sad.

But if there is even one little flicker of humor in this entire situation, it can be found in the many full-page ads the makers of Vytorin have been running in the New York Times and other national newspapers the past week or so in an effort to talk people out of quiting their drugs.

Says the ad:

Are you taking Zetia or Vytorin?

If so, you may be worried about recent news stories questioning the benefits of these medicines…on the basis of a single study that has generated a lot of confusion.

This is a fine load of bull coming from pharmaceutical companies that are more than willing to have you taking all these medications on the basis of a single study. I guess it all depends upon whose ox is getting gored.

Please note: I reserve the right to delete comments that are offensive or off-topic.

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24 thoughts on “A bad week for statins

  1. As a frequent reader and infrequent commenter let me say that I have enjoyed many of your responses to others comments and learned a great deal from them. Good luck on your book, future processing system and future post on the Fat Loss Bible.

  2. Back when I read about former astronaut Dr. Duane Graveline’s experience and belief that statins can cross the brain barrier to lower brain cholesterol, I was convinced of their dangerousness. I am concerned enough about what insulin is doing to my brain without having my brain’s cholesterol lowered.

  3. Last week when these articles broke in the NYT and Business Week I was perplexed and extremely annoyed with the fact that the NYT article appeared in the business section and the second article I read was from Business Week. I see you noticed this as well. The first article I read was the NYT article on the internet and at first I thought I was reading an article in the Health and Nutrition section until I noticed otherwise. This deflated my excitement a bit. These or similar articles need to appear in the Health and Nutrition sections of widely read publications where the majority of those that make the average family’s health decisions will actually see and read them. Don’t mean to stereotype anyone, but how many housewives actually read Business Week?

    Thanks for the great post.

    Mark

  4. Dr. Mike, you wrote, “As I reported in my post the only evidence that statins produce any decrease in all-cause mortality is in men under the age of 65 who have established heart disease. For women of all ages with and without heart disease and for men of all ages without heart disease, these drugs don’t bring about a decrease in all-cause mortality.”

    I know you have repeated this information until you’re probably sick of writing it. But when truth goes against dogma, it’s hard for people to wrap their minds around it. It has taken me a year to understand and internalize what you’ve been saying about the statins. Please keep up the good work.

  5. It continues. I keep getting more angry at the way things are. There are so few docs brave enough to tell the truth like you do. Heck, the way the system is, I’m convinced that there are a sinful number of docs that don’t even know truth. All they know is what the system pushes. It’s evil, I tell ya. Thanks again!

  6. I want to share a statin experience. I apologize for the length of the comment, but I think that the detail is necessary to give the whole picture of what the real consequences can be from simply being prescribed a billion dollar “wonder” drug.

    My life was turned inside out simply because of a routine checkup.

    Baseline stats: I am (was) a 56 yr. old male, sedentary (design at computer all day), normal libido, from the south, laid back not given to excitability, 6′, 212 lbs., long term smoker, genetic longevity, decent lung capacity, mean Blood Pressure 118/65 sitting and standing, pulse 64, no special diets (typical southern foods), no supplements, no problems other than occasional bouts with back spasms, no allergies, good EKG, good EEG, blood count normal, thyroid panel normal and liver function normal.

    BUT, a test said that I had “high” triglycerides 287, total cholesterol 149, HDL 37, LDL 55, glucose 89.

    I was put on Vytorin 20 mg =Tri. 175, TC shot to 214, HDL 40, LDL shot to 139.
    Then Vytorin 40mg = Tri. 199, TC 144, HDL 40, LDL 64.
    Then Crestor 10mg = Tri. 98, TC 141, HDL 45, LDL 76, glucose 103.

    I complained of losing energy and libido. I was told to exercise, I did and maintain 2 1/2 mile brisk walk each AM for nine months now.

    I complained of greater loss of energy and libido. I was put on Effexor XR 75mg (taking Crestor 10 mg)

    I complained of jittery feeling and restless sleep, increased Effexor to 150 mg and added Benztropine 1mg, Lorazepam 2mg (taking Crestor 10 mg).

    I reported no significant change, increased Effexor to 225mg, Benztropine 2mg, Lorazepam 4mg (taking Crestor 10 mg).

    I started having muscle and joint pain, added Darvocet to the cocktail, which curbed the pain, but had less energy and no libido (taking Crestor 10 mg).

    I was switched to Cymbalta 60 mg, Lorazepam 4mg and Darvocet (taking Crestor 10 mg).

    I started having anxiety and panic attacks (something that I had never experienced in my life), I had to cancel a business trip, because I panicked about being on a plane (I have flown my whole adult life), the doctor added Seroquill 100mg, increased Cymbalta to 90mg, Lorazepam 4mg and Darvocet (taking Crestor 10 mg).

    There was no significant change, so I was switched to Wellbutrin XL 150mg, Lorazepam 4mg and Darvocet (taking Crestor 10 mg).

    I had constant anxiety, no panic attacks, sweats, temperature sensitivity, weakness in legs, no libido, intermediate insomnia and started losing appetite and thus weight. Joint and muscle pain if I skipped Darvocet, increased Wellbutrin to 300mg, added Aderall 30mg and switched to Ibuprofen 600mg (taking Crestor 10 mg).

    Symptoms got worse, so I switched doctors. New doctor stopped Adderall, weaned me from Wellbutrin and started me on Prozac 20mg and Xanex .25mg. Anxiety became intermittent, but I continued to lose energy, lose weight, feeling weaker with joint and muscle pain. Prozac was increased to 40 mg. No change.

    I was switched to Paxil 20 mg; I had less frequent anxiety, but all other symptoms getting worse. Paxil was increased to 40 mg. This almost eliminated anxiety, only occasionally having to use Xanex, mainly to get to sleep at night, but waking up exhausted and wet clothes from sweating in the night. My fatigue and weakness were becoming debilitating with the addition of I was having problems with my eyesight at the computer and my sense of comprehension was waning greatly making it impossible for me to do my work. (Taking Crestor 10 mg).

    I was sent to a psychiatrist for counseling for depression. The Psyc. determined that I did not need counseling, symptoms were chemical and switched me back to Prozac 20 mg, replaced Xanex with Lunesta and put me on Provigil 200mg. I had a slight return of the anxiety, but was told to use Xanex in those cases. I began regaining sense of comprehension, but getting weaker, losing more weight, and the right tibialis anterior muscle started getting numb along with my right foot. (Taking Crestor 10 mg).

    My walking partner, a retired pharmaceutical sales person, commented that she was noticing foot drop in my right foot as I walked. We began discussing my whole ordeal over the course of the next few days. She asked if I was on a statin and I told her that I was on Crestor 10 mg. She asked if I was advised to supplement with Co-Q10, B-complex and Vitamin C and I told her no. She suggested that I do so immediately and go back to the doctor and revisit my symptoms with him. I had a visit to the Psyc. coming up soon so I did as she suggested. The Psyc. agreed with her supplementation suggestion and agreed that I should have been so advised, but praised the value of Crestor, especially in preventing Alzheimer’s. He increased the Provigil to 300mg. (taking Crestor 10 mg).

    Two days later during our walk, I collapsed due to weakness in my legs and knees especially and my right foot was paralyzed. After helping me back home my walking partner suggested that I wean off of the Crestor over 2 weeks, because a sudden stop could make me prone to a stroke, boost the CoQ10 and get to a doctor. I was scheduled to leave on a 4 week business trip immediately which I could not miss due to missing the last one, but I did as she suggested about the Crestor and CoQ10. During the first two weeks of the trip, the pain was almost unbearable (eating Darvocet, hydrocodone & ibuprofen like candy), I could hardly walk or get out chairs.

    My associates, who had known me before this incident, kept insisting that I looked like I had had a stroke or something due to my appearance, weight loss, diminished mental capacity and walking.

    Symptoms started improving drastically over the next two weeks.
    I did extensive internet research and interviewed people with experiences while on statins while on the road and since my return and found literally hundreds of statin horror stories and complete ignorance by the users of statins that the unpleasant onset of symptoms that they were having (depression, fatigue and pain) might be attributable to statins.

    Upon my return and relaying what I had found to my walking partner, she said that the drug companies knew that such side effects would occur and in fact played with combining CoQ10, B & C vitamins with their statins. They had started instructing doctors to suggest such supplementation upon prescribing statins. She said that it could take from 6 months to a year to recoup from some of the side effects based on reports that she had seen, but that extensive nutritional supplementation would help.

    Over this course:
    I have lost from 212 lbs. down to 170 lbs., lost muscle mass everywhere even down to my hands, lost close to 50% of my body strength, lost the ability to walk, concentrate and apprehend.

    I have lived with absolute fatigue, no libido, no appetite, depressive thoughts, anxiety, insomnia and horrible pain

    I have been diagnosed with and/or treated for GAD (general anxiety disorder), depression, insomnia, arthritis, ED, poked, prodded and told that “I was just getting old”. I have been sent to a shrink.

    I came close to losing my ability to make a living.

    All of this because of a number on a scale that prompted a doctor to put me on a statin, which I have found, through my exhaustive research, has no advantages in overall mortality rate.

    I am now back 5 days from the trip (Crestor free for almost 3 weeks now).
    I have begun a full regimen of nutritional supplements and healthier diet.

    I am back to walking the 2 1/2 miles again though my muscles get sore like they did when I had just started training.
    I have 75% use of my right foot back (getting better everyday), occasional pain running from my left hip to my knee.
    I am feeling a little better and stronger each day both mentally and physically, but absolutely paranoid about revisiting the doctor even to have my cholesteral checked.
    I am looking into chiropractors to deal with the pain in my left leg.

  7. Thanks for pointing it out, Dr. Mike.

    As to the business section vs. the medical section, Big Pharma is a how many billion dollars in revenue per year enterprise? I figured in your blog or Adam Campbell’s yesterday that Vytorin alone is a $5.5 Billion per year product ($3/dose, 365 doses, = ~$1100/year to patients and insurers, times 5 Million domestic patients… globally it’d be harder to figure since most civilized countries get their Vytorin through government purchase and therefore pay considerably lower prices). Despite relative smallness to the size of the GDP, this is still large change to anyone, including aviation contractors and film producers. And, since this is going to affect investors before it will affect general citizens. What was that arthiritis medication that got revoked by the FDA and caused a single day stock drop of 60+% for one company? It was an amazing destruction of value from a relatively small regulatory action (I think it was causing heart attacks or something). The reversal of thinking on statins and other cholesterol hypothesis is quite a lot wider than one drug at one drug company. We’re looking at most of a sector and the leading product category in the entire industry. That’s some major value disappearing. If my 401K had the ability, I’d make an effort to dump big pharma as a whole, but sadly, we don’t play like that.

    Meanwhile, on the health side, everyone and their mother is either in bed with the pharma companies or is effectively married to statins/lipid hypothesis to the point where reporting truth would be painful from an economic sense or from a credibility sense. How can a regular reader go back to Jane Brody after those articles about her decision to start statins that Dr. Mike posted on a few months back? You could only go back to say, “I told you so,” if in fact you did tell her so. I think I sent her an email. I never got a response… big surprise, right?

  8. As I have said for many years to anyone who has informed me that they are on statins, “you just wait…in tens years, statin drugs will be looked back upon as the single greatest medical hoax ever perpetrated on the American public.” It boggles the mind to think that some cardiologists still believe the population would be healthier if everyone took a statin as a preventative measure.

  9. “…In contrast, the only large clinical trial funded by the government, rather than companies, found no statistically significant benefit at all…” Can anyone cite this study for me. Thank u in advance.

  10. Oh my! Have you seen this article?!?! I’d love to see you post on this:

    http://www.theheart.org/article/839641.do

    From TheHeart.org, a discussion about the recent news articles about LDL and it’s value in treating heart disease.

    Essentially they’re saying it’s not how much you lower LDL as how you lower it, and statins are best for that…..and that the ENHANCE study was with “difficult to treat” patients and more normal people would have different results….and so on and so forth.

    For those following the link, registration is required, but free.

  11. Hi Dr Mike,

    My comment (first!) in your post “A statinator speaks”
    http://www.proteinpower.com/drmike/cardiovascular-disease/a-statinator-speaks/
    still applies: no conversation at all on this in the Australian mainstream media. Even now. Thank heavens for you and the internet. And for people like Regina on your blogroll. And for people like Dr Davis on her blogroll. You guys are giving us ahead of time what will be the received wisdom in the future (five years time?). Bravo. I’m convinced of this.

    Your only appropriate reply to this post should be your completion of your new book!

    Michael Richards

    Obligatory Music Comment:
    Check out http://www.overgrownpath.com/2008/01/so-you-thought-classical-music-was-dead.html
    Good post on another great blog.

    Michael Richards

  12. I was having a similar experience as Doug but mine started with hormone injections for a uterine fibroid which caused hypertension. I had every negative side effect to every class of meds for it and was told I had anxiety and was started on Xanax. I realized it was all med related and quit. Now my BP is getting lower every day and I’m using magnesium, CoQ, cinnamon and arginine. The meds made me sick and crazy and I still had hypertension. Their answer was of course “We’ll up the dosages and add some other BP meds too.”

    We have got to stop capitulating to these doctors when our bodies are telling us the truth. I knew to avoid the statins, thank goodness, as they would all have put me on them.

  13. Dave Dixon,

    Great hypothesis for CVD causation. You explained it in a very logical and easy to understand way, plus the use of the flowchart works great . Love your blog. It seems that we have lost the ability to do good science in this country. I put the blame on the education system. It is great that there are people like the Drs Eades and you, and all the other great thinkers out there in the blogworld who generously give of your time to educate those who want to be educated.

  14. Business Week is a very appropriate publication for an article questioning the effectiveness of statins to appear. Businesses have to pay attention to the bottom line. One of the reasons given (by the Auto industry) for our lack of competitiveness versus the Asian economies is our high health care costs. The overprescription of expensive, minimally effective or ineffective or , in the case of Doug, harmful drugs significantly contribute to these costs.

  15. I love this quote from one of the excerpts: “He found no benefit in people over the age of 65, no matter how much their cholesterol declines, and no benefit in women of any age.”

    Because women are entirely different from people.