Let’s close the chapter on statin safety

There was important news recently on statin drugs. As one of the world’s most effective and commonly used medications, statins provide great writing topics. Lots of people have high cholesterol–including cyclists. Lots of people are interested in avoiding our mostly deadly disease.

I’d like to tell you about a recently-published landmark study in the Lancet that should quell safety concerns over statin drugs.

The punch line after I tell you the study’s results are short and sweet. Scroll down if you wish. But first, statin drugs are misunderstood enough to warrant a little blog-like simplicity. Let’s start with some background.

A brief statin review

Statin drugs are best known for their cholesterol-lowering properties. The notion is simple: high cholesterol levels are associated with heart disease and stroke. Drugs that lower cholesterol figure to reduce heart disease.

For statin drugs this hypothesis proved correct–but most clearly for patients that already have heart disease or are at high risk for heart disease (diabetic patients, for example).

In a nutshell, statins are probably the most important pill a patient with heart disease can take. For these high-risk patients, the secondary prevention effect of statins are remarkable.

The statin intrigue

What’s surprising and intriguing is how statins confer benefit. It turns out that the cholesterol-lowering effect of statins is not likely how they prevent heart disease. This idea is hard to explain because statins simultaneously reduce both cholesterol levels and heart attacks. Here’s the thing though: patients at risk for heart disease derive benefit from statins regardless of their cholesterol level. Moreover, lowering cholesterol levels with non-statin drugs does not reduce heart attacks or death!

I have come to believe—and over-simplistically explain to patients—that cholesterol lowering is only a side effect of statins. Their real effect probably has to do with their ability to prevent plaques from rupturing and platelets from clumping in the inside of the blood vessel. Consider statins anti-inflammatory agents for blood vessels.

All this seems too good to be true. If these pills are as good as you say, let’s put them in the water or at least sell them over-the-counter. Heck, you can easily buy drugs that increase strokes, heart attacks, internal bleeding and even AF. Why not let patients buy a drug that has been shown to reduce heart attacks and strokes?

Well, there is a rub. Of course there is a rub; we are talking about pills here. Regular readers and most masters of the obvious know that swallowing a pill can’t solve heart problems.

Statin unknowns

Two major issues have suppressed widespread non-prescription use of statins. The first is safety and the second is effectiveness in lower-risk patients.

Let me readdress the effectiveness issue first. Though study after study unequivocally demonstrate that statins reduce heart attacks and strokes in high-risk patients, the evidence is less convincing for low-risk patients. Experts far smarter than I debate this issue and a discourse here is beyond the scope of this blog post. Suffice it to say, it’s not clear whether statins make a difference in patients with high-cholesterol but few other risk factors for heart disease. (Medical people call this primary prevention–using a therapy to prevent a problem in the first place.)

The most recent news story centers on the question of statin safety. Though these drugs remain one of the most studied and safest pills of all time, they are dogged by concerns over safety. I am not sure why this is the case, but my (admittedly anecdotal) experience holds that even educated people are frequently blinded to the benefits of statins because of exceedingly rare adverse effects. It seems a .001% chance of a serious adverse effect from the drug trumps its 25% reduction in the chance of dying from a heart attack. (Misplaced fear analogy: It’s like being scared of lightening but not potato chips).

The HPS statin studies are worth knowing about

The follow-up data from the Heart Protection Study sheds a bright light on statin safety. The mostly British researchers with the Heart Protection Study Collaborative Group have done a great deed. They continued following patients in the HPS (1997) trial for another six years after the 5-year trial was completed. Now, both doctors and patients have yet more reassuring news about the long-term use of statins.

Let me summarize what they found (you can read excellent summaries on Cardiobrief and TheHeart.org):

  • Published in 2002, the original HPS trial compared more than 20,000 patients with heart disease, peripheral artery disease or diabetes who took simvastatin 40mg (Zocor) daily to those who took placebo.
  • The results were breath-taking. Across every subgroup, including those with ‘normal’ cholesterol, patients on the statin drug suffered fewer heart attacks, strokes and deaths. Additionally, there was no evidence of an increase in liver failure, cancer or any non-heart related illness with statins.
  • Most recently, HPS investigators report on the long-term follow-up of these same patients. After the original HPS trial ended, researchers instructed patients on statins to stay on them, and control patients to start them. They then followed these two groups for 6 more years.
  • In 11 years of follow-up, the researchers found that the original benefits of the statins remained. (No further benefit was shown because equal numbers of patients were on statins).

The big news was this:

  • The incidence of cancer and non-heart related death was the same in both groups.

One can only hope that most can now agree with what distinguished experts, Drs. Payal Kohli and Christopher Cannon, wrote in an accompanying editorial:

…the long-term results of HPS suggest that the early benefit of statins is likely to be followed by a prolonged legacy period, with benefit maintained over time and that extended use of statins is safe with respect to possible risk of cancer and non-vascular mortality.

Let’s close the chapter on statin safety. Let’s mute the purveyors of misinformation.

Sure, there are some patients that cannot take statins because of muscle pain. That doesn’t mean, however, that statins cause permanent or irreversible health problems. This 11-year trial in 20,000 patients provide compelling safety results: statins do not increase the risk of death, cancer or serious non-heart-related illness.

Though I can’t answer the question of whether statins benefit low-risk patients, I now feel even more confident in saying that the long-term risks of statin drugs are not scary.

John Mandrola is a cardiologist who blogs at Dr John M.

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  • http://www.facebook.com/profile.php?id=558041620 Vikas Desai

    Frankly, I think sales of wellchol and zetia are mostly due to patients unreasonable fear of taking statins, they are so concerned over liver failure with statins and attribute every muscle ache to the statin drug. 

  • Anonymous

    Dr William Davies, Cardiologist (probably one of the best “anecdotal” witness would be a Cardiologist)

    I spend a lot of my day bashing statin drugs and helping people get rid of them.But are there instances in which statin drugs do indeed provide real advantage? If someone follows the diet I’ve articulated in these posts and in the Track Your Plaque program, supplements omega-3 fatty acids and vitamin D, normalizes thyroid measures, and identifies and corrects hidden genetic sources of cardiovascular risk (e.g., Lp(a)), then are there any people who obtain incremental benefit from use of a statin drug?I believe there are some groups of people who do indeed do better with statin drugs. These include:Apoprotein E4 homozygotesApoprotein E2 homozygotesFamilial combined hyperlipidemia (apoprotein B overproduction and/or defective degradation)Cholesteryl ester transfer protein homozygotes (though occasionally manageable strictly with diet)Familial heterozygous hypercholesterolemia, familial homozygous hypercholesterolemiaOther rare variants, e.g., apo B and C variantsThe vast majority of people now taking statin drugs do NOT have the above genetic diagnoses. The majority either have increased LDL from the absurd “cut your fat, eat more healthy whole grains” diet that introduces grotesque distortions into metabolism (like skyrocketing apo B/VLDL and small LDL particles) or have misleading calculated LDL cholesterol values (since conventional LDL is calculated, not measured).As time passes, we are witnessing more and more people slow, stop, or reverse coronary plaque using no statin drugs.Like antibiotics and other drugs, there may be an appropriate time and situation in which they are helpful, but not for every sneeze, runny nose, or chill. Same with statin drugs: There may be an occasional person who, for genetically-determined reasons, is unable to, for example, clear postprandial (after-eating) lipoproteins from the bloodstream and thereby develops coronary atherosclerotic plaque and heart attack at age 40. But these people are the exception.

  • http://www.facebook.com/people/RIchard-Feinman/100002248386290 RIchard Feinman

    How to “mute the purveyors of misinformation?”  Call them names?  Don’t mention studies that show no decrease in all cause moratlity.  Keep their papers from being published. Exaggerate positive results as “breath-taking.” Most of all, insist on a double standard.  Knock low-carb diets and other alternatives and claim they have health risks while none have ever been demonstrate.  Work with the AHA to mis-represent triglycerides and the limited affect of statins and high benefit from diet.  The key thing is “mute” the critics.  Never mind that after how many years of statins, you are not sure that they benefit low-risk patients even though others are ready to put kids on statins. 

    Wait! I have an idea.  How about engaging in a collegial dialogue with your critics. How about directly considering the limitations in the statisics on statin and discussing things professionally with people who have credentials. I know I’m incredibly naive. On the other hand, the door’s always open: feinman@mac.com

  • Michele Bordelon

    I’m curious about your perspective on statin impact on the body’s natural levels of CoQ10 – I’ve been reading more and more about this.  I watched as my normal blood glucose levels rose after being on a statin.  I had actually cleaned up my nutrition and yet my blood glucose took on a increased trajectory…as I was also losing weight.  I’ve since dropped that level back down through aggressive dietary adjustments however it still isn’t at its original level since before taking statins.  Coincidence?  I think not. I personally found this frightening. Unfortunately, not everyone is “frightened” into action as I was by having to go on a statin. And that’s what physicians have to deal with so often – Thanks for the interesting post.  I’m interested in your thoughts on CoQ10.  

  • Steve Wilson

    Hello Dr. Mandrola,

    I note that the study you referenced to support this guest post was funded by Merck, a major manufacturer of statins. Of course lots of studies are funded by major pharmaceuticals but there is a vested interest for the study to give them the results they want. This piqued my curiousity: do you receive grant support/consulting fees/lecture fees or any other payment/gratuity/benefits from the big players in the drug industry?

  • Anonymous

    Dear Dr. Manrola, many of us are concerned with the side effects of statins that most doctors dismiss.
    1. Depletion of CoQ10 – why have you not addressed that?
    2. Muscle pain and weakness – again why have you not addressed that?
    3.  Memory loss – see above!

    There is a lot of evidence linking statins with muscle problems and memory problems, why are no doctors investigating this.

    The usual conversation goes this way:

    Patient A ( on statins):  Doctor, I am having muscle pains and weakness.
    Doctor: Dear, you’re getting older.

    Patient B (also on statins):  Doctor, I am having memory problems.
    Doctor:  I suspect early onset of of Alstheimer’s.  I recommend starting A……t.

  • Anonymous

    Should have said Dr. Mandrola, sorry,,,,

  • http://twitter.com/drjohnm John Mandrola, MD

    Thanks for all the ‘robust’ comments.

    First the easy part: I have no industry relationships. I am just a clinician–a regular doctor. I see patients in the office, and ablate arrhythmias in the EP lab. That’s it. My blog has never made a dime. On the contrary, I pay for its costs myself. Like you would spend for any enjoyable hobby.

    Second: It’s ironic that some of the criticisms of my piece stem from my perceived advocacy of statin drugs. In fact, it is the opposite: I don’t like prescribing pills. I consider myself a crusader for healthy living. I believe the best way to prevent and treat heart disease is by consistently making good choices. [We] have yet to find the best means to get people on what I call the ‘program.’ (A side bar here is that I believe Ms Obama is on the right track–start with the new generation.)

    The purpose of my piece was to offer my take on recent evidence for statin efficacy and safety.

    Third: It is true that most of the statin trials are supported by statin makers. Such is an important thing to consider. But…Randomized placebo-controlled clinical trials that look at hard endpoints like death, stroke and heart attack are tough to rig. You would have to posit overt dishonesty of the investigators. Though I think researchers may occasionally exaggerate positive results in lieu of adverse effects, I do not believe industry funding leads to widespread fraud. I believe most in medicine and science are right-minded–human yes, but still right minded.

    Fourth: I concur with the notion that the debate on statins for low-risk patients continues. Most experts believe the reason statins show mixed results in low-risk patients stems from the low event rates in this cohort. It’s hard to statistically lower an already low event rate.

    Fifth: I have read about the CoQ10 depletion idea. Ideas like this are important. Ideas are always good. But thus far, I know of no trial looking at hard outcomes (death, heart attack, stroke) that shows a benefit to adding CoQ10. The danger of promoting ideas as sound medicine is that things that are theoretical, studied only in rats or observed in a chem lab, don’t always prove true when studied in real people. Examples abound here. Think anti-oxidant vitamins.

    Finally, If your doctor dismisses a potential drug-related side effect the solution is easy. Get another doc. One who listens; who discusses the evidence base; who partners with you and then allows you to choose your course. This is called patient-centered care. It makes for longer office visits.

  • http://www.facebook.com/people/RIchard-Feinman/100002248386290 RIchard Feinman

    “I know of no trial looking at …. studied only in rats or observed in a chem lab, don’t always prove true when studied …” I think most of object to closing chapters and muting critics. Information from “a regular doctor” and their take on recent evidence is of interest but may not be the only take or even the most informed take.  There are so many bookmarks, I would keep the chapter open.

  • Anonymous

    I think statins are one more BIG PHARMA fraud to make permanent patients out of normal people as described in such books as SELLING SICKNESS, THE TRUTH ABOUT THE DRUG COMPANIES and others.  It is well known that the committee making up (literally) the standards for prescribing statins mostly have drug company ties and these drugs while useless for many can have lethal effects like muscle DAMAGE.  BIG PHARMA has so corrupted the clinical/medical study process by corrupting the entire medical profession, academics and government to work as their paid shills that whether one of a million of their bogus claims is true or not, they are the proverbial “boy who cried wolf” now that everyone knows, “the emperor is wearing no clothes.”  On the positive side, there are great doctors like Dr. Joel Fuhrman who has written the wonderful books EAT TO LIVE and SUPER IMMUNITY on lifesaving nutrition to prevent and/or reverse most diseases along with a healthy life style including exercise.

  • http://profiles.yahoo.com/u/66NCFAXDWYB7JVNVNLNIUTCUVU Violetta V

    ts. It seems a .001% chance of a serious adverse effect from the drug
    trumps its 25% reduction in the chance of dying from a heart attack.

    Comparing absolute risk to relative risk reduction? Did they teach you the difference between absolute risk and relative risk in medical school?

    I don’t presume to know anything about medicine. Assuming your numbers are correct, the actual comparison would depend on one’s absolute risk of dying of heart attack. What is the absolute risk of the patients to which you prescribe statins of HAVING a heart attack within next 10 years? What is the absolute risk of dying from it? Please compare apples to apples.

    The funny thing is that when the doctors use the comparison above with the patients most patients would think they are almost certain of dying from heart attack within 10 years.

    BTW — it’d be always nice if you used a time period e.g. having a heart attack within next X years. The lifetime risk of dying is 100% after all, and heart attack isn’t the worst way to go….