Tuesday, February 16, 2010

Lipitor: Responding to Space Doc

I have now been blogging for over two years, and it has been quite an adventure. One of the best parts of blogging has been comments and communications from readers. Granted, the negative comments do take some getting used to, as the anonymity of the Internet allows some posters (though thankfully very few) to be somewhat blunt and in some cases rude. (I publish all comments that are not trying to sell something). However, the vast majority of comments and communications from readers, even when they disagree with my opinions, have been interesting and extremely rewarding for me; especially when it comes from a patient who feels like they were helped from one of my posts.

I received a recent email from a reader on my recent post Bad cholesterol not that bad? Shame on MSNBC...Again! That emailer suggested that I check out the work of SpaceDoc and cc'd him on the email. I subsequently received an email response from SpaceDoc himself. (I have posted his entire email below for fair balance). Rather then respond directly, I thought I would respond in a follow up blog post.

I actually became familiar with SpaceDoc when a close friend told me about her mother who had sudden memory loss with Lipitor. The doctor's web site www.spacedoc.net was Google's first hit. Spacedoc is really Dr. Duane Graveline, MD, MPH, a family physician who started is career as a US Air Force Flight Surgeon , and then went to NASA serving as a flight controller for the Mercury and Gemini program and was selected as one of NASA's six Scientist Astronauts in 1965. He then practiced many years as a community physician before retiring. However, Dr. Graveline is probably better known for raising awareness of side effects from statins. He wrote his first book "Lipitor, Thief of Memory" after having two episodes of something called transient global amnesia (TGA) which he states was associated with his use of Lipitor from 1999 - 2000. (A condition that was clearly the same as what my friend's mom had).

As a seasoned family physician and NASA scientist, I do not doubt Dr. Graveline's sincerity or integrity. Though I have not read the entirety of his work or reports, I do not question their veracity. Where I think we may differ is perspective. As someone who has now suffered several side effects from a statin medication like Lipitor, Dr. Graveline has personal reasons to be concerned, and why he now spends a significant amount of time looking into side effects of statins. However, in my experience I have prescribed thousands of statin prescriptions, and not seen these side effects. On the contrary, I have seen patients at very high risk for heart attacks and strokes live event free due to cholesterol levels at NIH goals. Furthermore, I worry about patients who are at risk and not at their cholesterol goals, particularly those patients who refuse to take statins because they worry about side effects.

As stated in my previous posts (and others), there are simply no medications that are completely safe. Aspirin and now Tylenol might never be approved by the FDA if they were submitted as new drugs today. In addition, in my opinion, any medication can cause any side effect in any individual patient. I never dismiss a patient who relates a certain side effect to a new prescription, though I will tell them whether their possible side effect is a known common, known rare or unknown side effect.

In my opinion, medications are all about risk/benefit ratio. And when it comes to statins, I have a really hard time coming up with a medication class that has a better risk/benefit ratio then a statin (please post a comment if you can come up with a drug with a better risk/benefit ratio then a statin).

Depending on the study you look at and how risky the populations statins reduce heart attack/stroke by about 5-10% (that's absolute risk, you would need to treat 10-50 patients for a few years to prevent 1 event) and reduce death by about 1% (need to treat 100 patients with a statin to prevent 1 death). The most common side effect is myalgia or muscle pain, which about 3% of patients will get, but this pain is usually mild and usually goes away. The rare and serious side effect that the TV advertisements warn of that could be related to muscle pain is called rhabdomyolysis. It is pretty rare (about 1 in a million), but is serious and 10% of patients who get this can die. However, using the FDA data that Spacedoc cites (below), from October 2003-2004, the rate of rhabdo was about 1/500,000 (not including Crestor). During that year there were 120 million statin prescriptions written. Given data that shows that patients on average fill their statin prescriptions 50% of the time (6/12 prescriptions per year), that would give a rough estimate of about 20 million patients on statins during that year (number is probably much higher). Using these numbers, with 20 million patients taking a statin, you are preventing at a minimum of 400,000 heart attacks and strokes and 200,000 deaths, but 40 people will get rhabdomyolysis and 4 of them will die from this. Even if you add up all the other rare and serious side effects mentioned by Spacedoc and others to the rhabdo events, the positive outcomes of statins are favored at least a thousand fold. These are great odds in my mind.

Research into adverse events is very important. One bad event is one too many. If we can figure out why some of these rare side effects occur, maybe we can prevent them in patients at particular risk. However, the media and blogsphere tends to focus on bad news. This news sometimes needlessly scares patients. One of my patients has high cholesterol, poorly controlled blood pressure, and has already had her first stroke. Yet, she is petrified of taking a statin because of everything she has "read and heard." This is why I am so concerned about articles like that mentioned in Men's Health and regurgitated on MSNBC. When it comes to medical journalism these days, there seems to be a major lack of balance. This leads to patients stopping or not taking medicines that can help them, and this will unfortunately lead to preventable heart attacks, strokes and death.



Email from Spacedoc:

Mathew,when you respond that statins are extremely safe and transient global amnesia is extremely rare I wonder how familar you are with the true spectrum of statin side effects. On the subject of TGA, do you know that over 1,000 cases of TGA have been reported to Medwatch over the time period 1998 to present and none of this as been reported to the medical commnity? Don't you wonder about this? And do you know that our thousands of of peripheral neuropathy cases are permanent? And of our tens of thousands of cases of myopathy, 68% will be permanent? And how about our over five hundred cases of disabling ALS-like neuromuscular degeneration (I happen to be disabled with this one but after three years of supplements I seem to be getting better. I still use a walker, however. That's why John Edwards MD of WHO called this "ALS-like" - different pathways and mechanisms may be involved). FYI about Medwatch not reporting I have attached my paper (with Jay Cohen MD as Co) done several years ago when our Medwatch count was 662 just for Lipitor. and remember this was just for amnesia not for the other lesser forms of cognitive deficit such as disorientation, confusion, forgetfulness, dementia and short term TGA measured in minutes not hours. Additionally I have copied you on my survey of other Medwatch data from the same CD that I took my cognitive data. And read this link below for an assessment of where I am right now on my statin research. It is a good concise paper.THIS LINK SAYS IT ALL ABOUT STATINShttp://www.spacedoc.net/mitochondrial_damage_introduction

46 comments:

gary said...

Matthew - I agree with you that medical journalism should be more balanced. Medical journals sould give appropriate space to Spacedoc and his peers to counterbalance the billions of advertising dollars spent by the Pharm companies. That's the only way medical news will be equally balanced.
gary
a second episode TGA patient, and former lipitor user. If you are in the 5% of TGA patients you are 100% affected!!!!!

Mike Cawdery said...

On the basis of the Heart Protection Study (HPS) I presume that you tell your patients that only 3 per 1000 per year will be "saved" while 5 times as many will die despite therapy; and of course, 982/1000 will not benefit in terms of death. Even over a 5 year period 15/1000 were saved, 75/1000 died despite therapy and 910/1000 did not need treatment. In diagnostic terms the risk estimate was 91% WRONG

And of course you will tell your patients that 50% more died in the JUPITER trial in the Crestor group than the placebo group. No wonder they terminated the study early based on statistically significant beneficial NON-FATAL secondary endpoints.
Oh yes if you do not believe me read the NEJM paper and its Table 3 very very carefully and then you can do a little arithmetic. While at the premature termination the death rate was not significant, death/hazard ratios are usually assumed to be constant over time. The result is that in later years this ratio becomes highly significant - something to be avoided at all costs - remember BAYCOL a statin that killed and was taken off the market! No wonder JUPITER was terminated early!

Also, Pharma companies are notorious for cutting studies off early when there's supposedly near-miraculous evidence of a drug's effectiveness. But that's a load of bull -- and a new study published in the Journal of the American Medical Association shows that the only miracle here is that these companies are allowed to get away with such shenanigans.

When researchers compared shortened studies to similar trials that went the distance, they found that the speed course exaggerated drug effectiveness by an average of 30 percent.

Some meds even looked twice as good in shortened studies, and other drugs managed to look effective when they actually didn't work at all. Talk about a miracle!

Dr. Matthew Mintz said...

Mike,
Death, while the ultimate endpoint, is very difficult to show statistical significance in any intervention trial. The study was not designed to show a mortality benefit. It was designed to show a decrease in cardiovascular events like heart attack and stroke.

About 5 years of statin treatment typically prevented these major vascular events in:


100 of every 1,000 people who have previously had a heart attack

80 of every 1,000 people with angina or some other evidence of coronary heart disease

70 of every 1,000 patients who have previously had a stroke

70 of every 1,000 patients with occlusive disease in leg or other arteries

70 of every 1,000 people with diabetes

Yes, that means that 930/1000 diabetics wouldn't benefit, but it still doesn't mean it's wrong. You need to look at the risk benefit ratio, and specifically in the case of statins, the risk benefit ratio is still quite good, because despite extremely rare events like transient global amnesia, most patient have no side effects from statins, with the exception of mild muscle pain which usuall goes away. Put another way, if you are a diabetic and there is a 7/100 chance your heart attack or stroke would be prevented, a 3/100 chance you might have some mild muscle pain that goes away, a 1/10,000 chance of something really bad happening, and 93/100 chance that the medicine won't harm you but likely won't help you, what would you do?
Most of my patients given these numbers would take the statin.

Regarding the JUPITER trial, here's the quote from the NEJM article:
"The trial's prespecified monitoring plan called for two interim efficacy analyses with O'Brien–Fleming stopping boundaries determined by means of the Lan–DeMets approach. The stopping boundary was crossed at the first prespecified efficacy evaluation, and on March 29, 2008, the independent data and safety monitoring board voted to recommend termination of the trial." This means they pre-determined when to stop the study and the decision was made by and independ group, not the drug company.
Finally, Crestor is not even close to Baycol. At normal doses you started to see myopathy and ast/alt elevations in 1-2% of patients. This should have been a signal not to approve the drug. Crestor, which is much more potent, was studied extensively post-Baycol and this signal was not found. Despite pressure from Sidney Wolfe, the FDA looked at the data extensively and found no problems.

Robert said...

A consumer's perspective:

As a consumer I give little to no credibility to drug company funded studies.

Conflicts of interest run high in the JUPITER STUDY since it was authored by the man who receives royalties from the CRP test, and sponsored by the company that sells the pills.

The actual NNT scores from JUPITER in table one endpoints are extremely high (120, 288, 241, etc) giving Crestor absolute risk reductions well below 1%.

When looking at individual patients it becomes impossible to prove a fatal event was averted simply because they were taking a statin.

However, we can better measure the effectiveness of statins by looking at the population as a whole, and examining changes in trends of death rates from coronary artery disease prior to, and after the introduction of statins. This gives us a 40 year time line and the BIG picture.

Using graphed data from the Centers for Disease Control, and provided that data is accurate, there in no change in the downward trend of death rates from coronary artery disease for a period of 20 years prior, and 20 years after the introduction of statins.

Due to high patient complaints of "debilitating" side effects, sky high NNT scores, and no visible enhancement of reducing death rates on CDC graphs, this consumer views the Risk/Benefit ratio of statins as among the worst the industry has to offer.

Just one consumer's perspective.

Thanks for allowing me to share my viewpoint on the matter.

Robert said...

My consumer perspective on the risk/ benefit ratio of statins:

I never gave much credibility to drug company sponsored trials. Conflicts of interest run high. JUPITER was authored by a Dr. who receives royalties from CRP testing, and the trial was sponsored by the company selling the pills.

Statin drugs have always had very high NNT scores. The JUPITER trial actual 1.9 year NNT's are High ( 288, 241, 120) making absolute risk reductions well below 1%.

When looking at individual patients it becomes impossible to prove a fatal event was averted because they were taking a statin.

However, looking at the population as a whole, we can measure the effectiveness of statins by examining changes in trend of death rates from coronary artery disease prior to, and after the introduction of statins. This is a 40 year timeline and shows the BIG picture

Using graphed data from the Centers for Disease Control, there is no visible change in the downward trend of death rates from coronary artery disease for a period of 20 years prior, and 20 years after the introduction of statins.

Absurdly high NNT scores, High rates of consumer complaints from side effects, and no visible enhancement on the decline of death rates over the last 20 years doesn't exactly sell me on spending my money on these drugs.

My opinion on the Risk/Benefit ratio? You would be hard pressed to do much worse.

Dr. Matthew Mintz said...

Robert,
Thanks for your comments. First, you should realize that almost all data on drug therapies comes from the drug companies. NIH or other non-biased groups simply don't do this kind of research.
Not sure what your exactly looking at on the CDC website. Please provide the link. Better sources for this would be National Center for Health Statistics and NHLBI.
Most data show an increase rate in decline for CV death, particularly if just looking at myocardial infarctions, and many experts attribute this to statins.
Also, even if we assume that there has been a steady decline in death from heart disease before and after the introduction of statins, your logic is flawed because there are many things that have dramatically increased (obesity, diabetes,etc.) which would increase ones risk for death from heart attacks. Thus, a steady decline would be unexpected without statins.
Even if statins showed absolutely no mortality benefit, you are completely discounting their clear benefit in preventing heart attacks. Don't know if you have ever had a heart attack, but they are very scary and costly life-altering experiences in which most patients have decreased functioning if they survive. If statins can prevent heart attacks and not save even one life, they are worth it.
Finally, "high patient complaints" is not based on any data. If you look at all the data, the side effect profile of statins is pretty good. In the JUPITER trial there were no side effects compared to placebo. No side effects in the thousands of patients that took a high dose statin.

Robert said...

Dr. Mintz, Thanks again for allowing me to post my consumer view on statins.

At bthe bottom of this posting is the link you requested. I had said" CDC Graphs." That was my typo. I meant to say NIH.

NIH publishes a web page with the graphs I was referring to. Its a long page, so you will have to scroll down to access the heart attack graphs. There are five graphs:

1. Deaths from cardiovascular disease U.S. 1900-2005

2. Death rates from cardiovascular disease U.S 1900-2005

3. Age adjusted death rates of cardiovascular disease. U.S. 1950-2005 ( this is the main graph I am referring to. pay attention to 1968 to 2000)

4. Death rates in men, selected countries.

5. Death rates women, selected countries.

I am merely pointing out my observation that statins introduced around 1990 had no impact on the downward trend in death rates from coronary artery disease in every single graph.

Its not complex. A high school student is capable of making this observation.

Has someone somewhere benefitted from statins? Perhaps. But on the big scale, I don't view the drugs as making any impact on the population as a whole.

Here is the link:
www.nhlbi.nih.gov/about/factbook-07/chapter4.htm

Dr. Matthew Mintz said...

Robert,
Thanks for the link.
1. Do you not acknowledge heart attack and stroke are significant? You keep referring to death as if anything that doesn't decrease death is worthless.
2. Your logic that statins have no impact on mortality because the steady decline in CV death is unchanged pre- and post-statins is flawed. What do you attribute this decline to? Clearly it's not because we are healthier than we were in the 50's (with the exception of smoking). Let's say smoking has affected this (and it has). What you would see is a decline in the CV death rate from 1960-1980 or some other time point, but eventually the decline would plateau, since smoking (or any other single factor) attributes only a certain percent to CV death. In fact, we continue to see a steady decline year after year. And the reason is complex. It is not just one factor that has led to this, but many factors which we continue to make improvements in. It's better inpatient treatment of MI's (before most patients admitted with a heart attack died, now most do not), better blood pressure control with medications, use of aspirin, and very importantly statins. Ask any person with a medical degree, even the most unbiased, anti-pharma, liberal physician; and they will tell you that statins have played a major role in reducing CV disease, including death.
The real issue is not whether statins are good/bad, but what is the true risk/benefit ratio for the drugs. The answer lies somewhere in between we should put statins in the water to only use them in patients with extremely high risk for heart attack and stroke.

Robert said...

Dr. Mintz,

Absolutely heart attacks and strokes are significant. In no way was my observatation of the steady decline in CV death rates pre and post statin meant to minimize the significance of these events.

Once again, I am simply pointing out an observation that the introduction of statins around 1990 did nothing to enhance the decline rate on the population as a whole.

To answer your question, I believe the decrease in smoking is primarily responsible for the decrease of CV deaths from 1968 to 1990, and continued to have a positive impact all the way to year 2000. The smoking decline rate graphs correspond beautifully with the reduction in CV death rate graphs.

I would also agree that medical intervention to save lives has improved over the years, contributing to the decline.

But I don't view statins as having a role in the decline. But hey, thats just my opinion. I'm just sharing my viewpoint. Didn't intend it as a debate.

Robert

Linmalki said...

I am a "heart attack survivor"--nearly ten years and pretty much unimpaired. My cholesterol level was in an average range at the time. I was put on Mevacor (of course). In about 2 1/2 years I was experiencing severe, debilitating muscle pain and very noticeable memory loss. Having read about the possible relationship between statin drugs and memory loss, I discontinued taking the med. In about two weeks, I could feel the fog clear from my brain and the muscle pain was almost gone(although it took a year to regain full range of motion in my arms). I also had great frustration in getting my doctors to take my experience seriously. I personally know other people which similar experiences, most of which, again, are not taken seriously. A cousin, also in his 60's, who had a heart attack about the same time as I did, scared me the last time I saw him. He took almost four hours to make a trip that normally took 45 minutes because he got on a wrong road and wouldn't believe my repeated attempts to tell him, and then couldn't remember how to find the place we were going--somewhere he had been a number of times before. He is on major statin meds and he and his doctor don't believe he is impaired. His family is very convinced and very worried.
The point of overall mortality rate information compared to CV deaths is significant, as statin drugs do affect other physiological processes. Based on my own experiences and a number of other friends and family members, I am not convinced that statin drugs are worth the risks.

Dave said...

Hello, Dr. Mintz. I'm interested in this subject and so found my way here.

I'm interested because I think I am one of those people who have had a side effect from my medication/s.

While it may be true that each individual side effect is extremely rare, perhaps these side effects in aggregate outweigh the benefits. If that were to be true, then statins would not be such a bargain.

Specifically, I had rhabdomyolosis about six weeks ago, and the consequent myoglobinuria that lasted for at least several days.

And I've just gotten it again, three days ago. I'm just not sure why.

I am 62 and I had a heart attack a year and a half ago, with one stent placed in a coronary artery. I was placed on statins after the heart attack, and with my cardiologist's permission earlier this year, I've been taking niacin (my cardiologist prescribed 2000mg a day, which seems high, now that I've looked into it).

One year ago, I needed two additional stents. To me, it seemed that my statin had failed.

Dr rajiv Khanna said...

Dear Dr Mintz,
I am a Senior Surgeon 51 M who was detected to have DM Type2 2002. I started on intensive glycemic control. BP control atorvastatin 20 mg. My numbers have been good tc 150 ldl 100.i also excersised. lost weight 10 kg bmi to 26
In 2010 i had atypical choking symptoms with normal ECG and troponin. I had a thallium scan reported as Normal. A ct angio shows stenosis 50 -60 % rt coronary with soft plaques my atorvas was doubled within three months i am almost crippled with msc aches and weakness there has been msc wasting
As an individual i am disappointed that after all these measures i still seem to have significant cvd i am not sure statin did anything for me except take away my qol .

Dr. Matthew Mintz said...

Dr. Khanna,
There is significant evidence to suggest that the Lipitor may have prevented a heart attack or stroke in you. Only Crestor at max dose has shown the ability to possibly reverse plaque.
Since you have known CAD and high risk, you should be on the highest possible statin dose that you can tolerate. You should ask your physician or cardiologist to go back down on your Lipitor dose or switch to Crestor.

Dr rajiv Khanna said...

Dear Dr Mintz,
I highly appreciate prompt response,
My only question is having started statin therapy eight years ago and lifestyle measures i cannot imagine the plaques existed eight years ago and they just stabilized although i seem it have significant single vessel stenosis with a normal perfusion scan. I am concerned at the apparent progression. If the quality of life deteriorates to the extent it has to reach ldl levels i being a medical professional myself have to question the validity of this treatment. I have many friends in the invasive cardiology circles they all are aware of msc problem but sort of dismissive, I have researched many net clinical trails report low incidence of AE however the patient community including myself ie any one and anybody taking statins experience msc problems over time i would be appreciative if the medical community address this in objective manner and not suggest crestor with mac and fries
thanks
regards

Anonymous said...

Dr. Mintz,

There is NO EVIDENCE that the statin prevented a major heart attack in the poster above. It is impossible to prove that a cardiac event didn't take place because a person was takinga statin. Why would you make such an irresponsible statement?

Mommy Phyllis said...

This is interesting reading but as a person who, just three months ago, had only leg weakness and pain to complain about - and am now debilitated by pain and weakness in both arms, neck and shoulders, I can safely say I am sure I am suffering statin side effects.
Doctors and drug companies may agree or disagree, but we patients are the ones suffering and waiting for some kind of support and treatment. The worst part of all this is the ignorance or stubbornness of the medical community which (for the most part) denies the relationship of muscle pain and statins, and then offers no 'cure' for the side effects except perhaps some vague suggestion of supplements and the passage of time. No one speaks of alternatives to drug therapy for high cholesterol. If given a choice of suffering with this constant pain or having the potential for a heart attack, I'd likely take my chances for the latter. I may not die, would have some medical support, and perhaps would recover and be better for the experience. When you haven't the strength to lift up a coffee cup, you see things from a different perspective. Why doesn't the medical profession encourage better lifestyle choices - the ones we know will lower our cholesterol in natural ways? Instead, they just prescribe Lipitor and send you on your way...
It's unlikely a person would equate the pain and weakness they currently experience with a drug they have been taking 7 days a week, 365 days a year.
I wish my doctor would have been brave enough to equate my symptoms with Lipitor's listed side effects. Instead, he set the wheels of referrals in motion: orthopedic surgeon, MRI, x-rays, chiropractic, physical therapy.
I can't help but wonder if my physician were better informed about these side effects and had taken me off the statin months ago, would I now be closer to recovery (if recovery is possible)?
Thanks for allowing my post.

Anonymous said...

Phyllis,

I feel for you and muscle pain you are feeling. There is a simple formula to get physicians to listen to the patients. Spend more money entertaining your physician than the drug company does. I say that light hearted, but in reality its a sad truth.

We live in a world where money talks. That is reality. If the public really wants to get physician attention on the reality of statins, refuse and/or block payment to any physician who writes you a prescription for a statin drug.

Oh trust me, if everyone did this, patients would now have their doctor's attention.

Dave said...

"the ignorance or stubbornness of the medical community which (for the most part) denies the relationship of muscle pain and statins"

This is simply not tur. What evidence is there for this assertion, "Phyllis?" In fact, just a few months ago, the FDA sent out an advisory about the potential side effects of Simvistatin.

"Why doesn't the medical profession encourage better lifestyle choices - the ones we know will lower our cholesterol in natural ways? "

Another very suspect comment. Every doctor tells her or his patients to make better lifestyle choices.

Anonymous said...

Those who turn a deaf ear to patient suffering from statins, will one day cry themselves, and not be heard.

Dave said...

By the way, Mommy Phyllis' comments, above, about suffering side effects from statins, are also suspect for another reason:

When you click through on the links provided, you travel to a slick looking website that makes money by selling food supplements to offset the side effects of statins.  

So "Phyllis''" anecdotal evidence about statin use should be taken with a grain of salt.

I am still thoroughly confused about the efficacy of statins. I've had rabdo (admittedly after very prolonged physical activity). A few months ago my doctor switched me to a different statin, after the FDA warned a high dose of Simvastin could lead to muscle pain, which in fact I experienced. 

I'm sure, Dr. Mintz, that researchers thought Simvastin was nothing like Baycol. Yet we see that the are problems with Simvastatin, too, that have come to light with real-world use of the drug.

My dad had heart disease. I know I have plaque in my coronary arteries. I had a heart attack. Plaque in other areas of my coronary arteries necessitated two more stents eight months after my heart attack (and I was on 40mg of Simvastatin at the time). 

On the other hand, my cholesterol readings WIITHOUT statins  are normal, my c-rp level is normal, I'm not overweight, I eat well, and I can ride my bike 100 miles in a day. And my heart attack came after more than two years of serious daily personal stress. 

While my genes are the same, the stress is gone, so I wonder if statins are of any benefit to me. 

I worry about underreported side effects, like my muscle pain. When in saw my cardiologist and asked him about the Simvastain warning which had just come out, he told me, without questioning from me, that reports of muscle pain were underrated. And he thought the weird muscle pains I reported to him - painful arm and shoulder muscles on wakeup - were related to my statin use.

Sometimes I feel like I am a global warming denier, when I think statins are dangerous drugs that only make money for drug companies, while helping only a few high risk patients. 

At other times, I think that not being able to ride my bike anymore because of clogged arteries is a good reason to take the high dose of the statin I'm on now. The reputed potential ability of 80mg of a statin to halt or reverse the growth of plaque seems like a good reason to take the drug.

In any event, I see compelling but contradictory evidence offered from both sides of the debate about the efficacy and safety of statins. Given that my own condition seems atypical from those who are tested with statins, I do worry about their effect on me.

However, I don't worry because of comments by posters like "Phyllis."

Anonymous said...

Dave, my hat is off to anybody who can ride their bike 100 miles in a day. Wow, I'm impressed.

I'm also anxious to see how Dr. Mintz responds to your post. Excellent post by the way.

Your situation reminds me of stories I have heard about where marathon runners with no risk factors develop artery plaque. It serves as a stark reminder to me that we still have yet to nail down a definitive underlying cause for atherosclerosis.

I wish I had an answer for you.

My dad had heart disease too, Ultrasound shows my arteries clean and clear. I can't tell ya why. I have hypothyroidism, high triglyercides, cholesterol ran around 240 most my life. No known heart disease.

Its frustrating to figure out why one guy gets heart disease and the other doesn't, but I myself have given up on serum cholesterol levels having anything to do with it.

I wish you the best whatever you decide concerning taking the statin.

Dr. Matthew Mintz said...

@Dave,
There is still so much we don't know.
Regarding simvastatin warnings, they were there, but not taken as worrisome by the FDA. The issue with simvastatin is with the higher doses, and the problem is that in order to achieve LDL goals for many, you need the higher doses. Even Dr. Nissen, who I often disagree with, raised early concerns about simvastatin at the higher doses. Somewhat paradoxically, it seems that the more potent (newer) statins, cause fewer side effects. Lipitor only starts to potentially show problems at the 80mg dose. Crestor 20mg (which is just as potent as Lipitor 80mg) showed no side effects (compared to placebo) in the large Jupiter trial.
I think what we are seeing is a gradually increasing concern on the part of the FDA when it comes to adverse events. (In some instances, I believe they are actually going too far, but that's another post).
Now, regarding the marathon runner/100 mile bike rider with heart attack risk, this gets to my first point about how much we don't know.
Today it is reported that HPV may not only increase a women's risk of cervical cancer, but also increase risk of heart disease. The theory is increased inflammation. The aforementioned JUPITER trial with Crestor was stopped early because patients with relatively normal cholesterol but high CRP (marker of inflammation) had fewer heart attacks. Finally, the Vytorin fiasco happened because a trial showed that adding a non-statin, cholesterol lowering medicine lowered the LDL (bad cholesterol), but did nothing to progression of artery disease.
In total, statins may be more about decreasing inflammation and/or stabilizing plaque then reducing LDL and plaque build up. Thus, any one with known heart disease (stents being placed) or a cardiovascular risk equivalent (diabetes), should be on a statin, and probably a potent statin like Lipitor or Crestor.

Mommy Phyllis said...

I'm sorry, but I don't understand why Dave seems to negate every aspect of my post. Since he, himself, has had statin side effects, I cannot understand why he is denying me the right to share my story, give my opinion and try to warn others about potential muscle weakness and pain.
The "evidence for my assertion" that the medical community denies the correlation of statin side effects to muscle weakness is based on my own experiences with no less than three medical professionals - all of whom knew I was on Lipitor and all of whom referred me to other specialists for various expensive tests, rather than suggest my pain might be a side effect.
My doctor put me on Lipitor three years ago. There was no discussion about lifestyle changes, whether Dave thinks 'all doctors' tell their
patients to eat better and exercise or not. My cholesterol was high, my father had his first heart attack at 42 and "we needed to get my numbers down as fast as possible." So I took the Lipitor and one year later began complaining about leg weakness and pain. Three years later, I am virtually crippled every morning and only feel some relief by mid afternoon (after ibuprophen).
It's insulting and rude to say my personal pain and experience and opinion is "anecdotal." I guess that means that Dave's is as well.
I have no idea what links or ads Dave is referring to, or what it has to do with my point here, but I think Dave should take his bike 100 miles and not come back.
How ridiculous for him to go on an on about his own experiences and side effect pain and then deny someone else's similar story.
And as far as I know, there's no one offering any advice about how to recover other than what I stated before: supplements, time and maybe prayer.

Dave said...

Dr. Mintz, thanks for your reply. I appreciate your good efforts and you've presented a lot of good information on your blog. I hope you can keep it up.

You wrote, "statins may be more about decreasing inflammation and/or stabilizing plaque then reducing LDL and plaque build up."

That still makes it tough for me to decide about my medication. If my heart attack a few years was caused by stress (I don't know that it was, but I do know I had unrelenting stress for the prior two years), and if my cholesterol and c-rp levels were/are normal, then why bother with the expense and potential side effects of statins?

If 40mg of Simvastatin didn't stop my plaque from growing (I needed two more stents eight months after my heart attack), will 80mg of Lipator stop the growth?

If Lipator can't stop plaque from growing, then again, why am I taking it?

To my untutored mind, it seems that taking aspirin (and Plavix or Effient or some similar drug) is what's keeping me from having another heart attack. because those two medications keep me from clotting at the location where a piece of plaque might break off.

Also, if there is a tiny imperfection in my tiny stents, then aspirin and Plavix should help keep a clot from forming.

Of course, I don't know and probably can't know if a statin is halting or reversing my plaque. And statins seem to be tested on people with special problems, such as high cholesterol and/or high c-rp levels.

I don't see studies about the effects of statins on people with normal cholesterol/c-rp readings, who have or who have not had a heart attack.

For that matter, I haven't seen studies about the effects of statins on people who have had high degrees of stress, who have or have not had heart attacks. (Nor do I think such studies are even possible, stress being such a subjective condition.)

In any event, the studies I've seen seem to be directed toward people with anomalous conditions - diabetes, super high cholesterol, high c-rp levels, etc.

So the value of statins to someone like me still seems unknown. However, because I still want to be able to ride my bike 100 miles in a day, I am, for now, still taking 80mg of Lipator, in the hope that it will keep my plaque from growing (apparently, as of a few years ago, I had several areas of plaque blocking 20% of the flow of blood through my arteries).

I'm not happy about taking statins, though, because I'm also afraid taking statins might cause me to stop riding my bike, from muscle pain, from rhabdo (both of which I've experienced since being on statins, whether or not statins caused those things to happen), from transient global amnesia, etc.

No need to reply to my comments, Dr. Mintz. I do find that this is a good place to put down my thoughts about a class of drugs that seems to be beneficial for various classes of people, but not necessarily efficacious for every individual.

I look forward to more of your postings.

Dr. Matthew Mintz said...

Dave,
You are right. There are still a lot of unanswered questions, especially for someone like you who has a particularly unusual situation.
One thing to consider:
Risk of rhabdo is 1 in a million. Myopathy (muscle damage) is more common, but still on about 1/10,000. Myalgia (muscle pain) is the most common side effect, which is usually mild and usually goes away. In most cases (even with rhabdo) if you stop the statin, problem is usually solved. Thus, if you are taking the Lipitor and not having any muscle pain, there shouldn't be anything to worry about. It's is pretty uncommon to be on a statin for years and suddenly develop one of these symptoms.

Anonymous said...

Dr. Mintz, I think Dave makes some very good points about his situation.

He states CRP has been normal so what value would the statins ability to reduce inflammation be for his situation?

He states his cholesterol isn't elevated so what value is there in lowering it?

And Dave is right about the studies. I am not aware of ANY statin studies that fit his individual situation.

As far as lipitor's efficiency, I myself have never heard any claims of Lipitor inhibiting the growth of artery plaque. I do see the claims of Lipitor lowering cholesterol, and claims of reducing events, but again I see no claims of slowing plaque growth.

I think Dave's concerns for the risks are legitimate, especially since he had already experienced problems previously on the lower dosage.

Its ironic just today there was an article in the news about a bunch of young people developing heart disease that had no risk factors. Their artery walls are thickening despite normal cholesterol, normal blood pressure, normal weight, normal everything.

I think this demonstrates how little we know about this disease. As one doctor said "We are not as smart as we think we are" I would agree.

As for the statins, its normal for anyone pushing any product to portray their product in a more favorable light than reality.

To date I am unaware of any magic pill to ward off heart disease.

Dave said...

Anonymous wrote:

"I myself have never heard any claims of Lipitor inhibiting the growth of artery plaque."

There is such a claim. From a press release by Pfizer in 2006:

"The REVERSAL trial ...In a subset of high-plaque burden patients, Lipitor demonstrated a 5.9 percent … total plaque reduction with excellent toleration."

And here's a link to a news article, again from 2006, about Crestor's ability to regress plaque:

http://www.medicalnewstoday.com/releases/39470.php

The problem with the above study was the lack of a control group. So I'm not sure it's possible to say exactly what caused the reduction of plaque.

Nor am I sure what a "subset of high-plaque burden patients" means.

Dave said...

Dr. Mintz,

1) I'm going to stay on my statins.

2) Do you know how fast plaque grows in arteries, on average?

I had a heart attack in Dec., 2008. My dr. told me I had a 70% blockage in a small area of my left coronary artery that he didn't remove.

Eight months later, I had two more stents placed after I had some chest pain (while riding my bike at 9,000 feet above sea level). A few days later, I had two areas of 80-90% blockages stented. I was told i also had several small blockages that were 20%.

I've felt great ever since.

If my 70% blockage went to 80% in eight months, then I'm thinking my 20% blockages could, if the growth rate remains the same, now be at 40%. That means my blockages could be at 80% in about four more years.

If statins can slow or even reverse the build-up of plaque, then taking the drug, despite the side effects, seems worthwhile, at least if I want to keep riding my bike without chest pain.

If statins can't halt plaque buildup, then for someone like me, statins would seem to be of far less value.

And I just haven't seen the evidence that statins can stop/reduce plaque in someone who has normal levels of cholesterol and c-rp.

For now, though, I'm willing to bet that statins can reduce plaque (which I know I have).

So, again, are there estimates of how fast existing plaque can grow in arteries?

Dr. Matthew Mintz said...

Dave,
There are very few studies that look at whether or not statins can stop/reduce plaque in patients at high risk, let alon in someone who has normal levels of cholesterol and c-rp. In your previous comments, you mention REVERSAL and the Crestor study, which are the two main ones. Also, of note, that these were very high doses of potent statins. See this link for some more info http://www.theheart.org/article/662781.do

Of note, in the Crestor/ASTEROID study all patients were statin naive, but the mean LDL was about 130. This means that many of these patients could have been like you, i.e. established blockage with normal cholesterol.

As far as rate of progression of atherosclerosis it is very slow over years and years. I don't know how your cardiologist determined you went from 70% blockage to 80%, but if it was through an angiogram, these numbers are not very precise. The only way you can really get at actual blockage is through the IVUS method mentioned in both previous studies. Most cardiologist don't do this routine. Thus, your 10% change could have been as much as 20% or as little as virtually no change.

Dave said...

OK, I probably shouldn't respond to Mommy P's latest comment. However, for the few of us still here, I will.

First, I apologize for offending you, Mommy P.

However, this is the Internet, and we can be snarky behind our anonymous personas. Well, you can, since I have revealed who I am.

"I don't understand why Dave seems to negate every aspect of my post."

I'm not. I'm commenting on parts of it I don't think ring true. As you noted later in your last post, I've agreed with you on some things.

"My doctor put me on Lipitor three years ago. There was no discussion about lifestyle changes"

Mommy P, unless you were taking notes at that meeting with your dr., when you were prescribed Lipitor, I doubt you could remember what you WEREN'T told. And I doubt you took any notes.

You had some expensive tests. What were they for? And what were the results?

And how old are you? How do we know you aren't just suffering the effects of simple aging, lack of exercise, and/or poor eating habit?

Maybe you have arthritis. Maybe you have a form of neuropathy.

"I wish my doctor would have been brave enough to equate my symptoms with Lipitor's listed side effects."

We'll, there you go. The side effects were listed, and you failed to figure it out, until three months ago, when you suffered debilitating pain.

If you google "statin," every webpage that is linked to on the first page of google lists the side effects of statins, including the drug companies. Except for the very old and the very young, and the mentally challenged, everyone can use google to look up things like the side effects of drugs.

As to the link I refer to, it's the link that's associated with your name on this web page. If I click on your name, I can see another web page where you are the claimed blogger for "Life in Experiment."

OK - so I'm not saying you don't have pain. I do challenge your assertion that the medical community, which is a kind of nebulous term, doesn't inform the public about the need to lead lives that include healthy foods and exercise.

And I wonder about that link to the website which you indicate you publish. It's quite a blog - 15 posts alone today.

Anonymous said...

I have a medication that has absolutely no harmful side effects and many more benefits than statins. It's called DIET and EXERCISE.

Oh, and those figures that you like to cite? Those are only the effects that we KNOW of and are DOCUMENTED. How often do we find out that certain drugs are causing severe side effects over the long-term? Hmmm... constantly. How long have statins been around? A few decades? And we're already finding this many problems with them in the short term? Doesn't look promising to me.

Maybe doctors should start looking at treating their patients health instead of pumping them full of drugs. God knows every time I go to a new physician I walk out of the office with three new scripts.

bella said...

My mother has been taking Zocor for at least 10 years if not 15 years, and her memory and overall mental function has been declining vertiginously. A few month ago we received a letter from her cardiologist stating that Zocor could cause dementia and to stop taking it. Based on her decline I believe that her mental status was affected by Zocor, and her breathing and pains are most likely due to Zocor too. Big Pharma cares about big dollars! With diet and exercise we could have done more good than with zocor. It seems to me that dr. Matthew Mintz advocates the drug even though few people die or have declined in their mental status. To him, it doesn't matter if one in 1000 dies, unless that ONE is YOU! There IS NO PROOF that the 3 in 1000 people saved, could've not been saved with lifestyle changes either! The doctors receive many perks in order to write many prescriptions. Read Dr. Jerome Groopman's book: How Doctors Think!

Dave said...

Interesting comment, Bella.

If 3 out of 1000 people whom a stain helps could have changed their lifestyle, that would be awesome.

Only, in the real world, that doesn't happen.

There are always going to be people who are overweight and, for whatever reason, can't exercise - illnesses, accidents, etc. So the benefits of exercise will be lost to them.

There will always be people who have super-high cholesterol, despite diet and exercise.

There will always be people who don't process food as efficiently as others. They will always be overweight.

Food isn't just cheap, it's easy to come by, and it's tasty. We're programmed, genetically, to crave tasty food. We're programmed to be hungry for any kind of food, because we evolved in a world where there were no McDonald's, where getting enough food was a much-of-the day, life-long process.

There are all sorts of "if only" situations. If only all nations could stop having wars, if only we could practice racial tolerance there would be no hate crimes, if only we didn't drive too fast or drive drunk we wouldn't have to pay extra for seat belts.

Well, this isn't an ideal world, because we do drive too fast - it's why we have seat belts. We can preach tolerance all we want, and there will still be crimes against people based on the color of their skin or religious beliefs (or lack thereof).

And we aren't going to stop people - one out of three in the U.S? - from eating enough to become obese, nor make them exercise enough to lose the weight once they become overweight.

"With diet and exercise we could have done more good than with zocor."

Maybe. There's no way to know, though.

Anonymous said...

In response to Bella's post: The brain is the one organ most dependent upon cholesterol. Roughly 25% of the body's cholesterol is in the brain. The brain depends on cholesterol to function properly. It even makes its own cholesterol.

A process called synapses in the brain uses cholesterol. This is nerve signaling between cells, or cell communication. This aids in memory and cognition.

Cowboy Willie said...

Dr. Mintz,

I was on Lipitor for four years. I complained to my cardiologist that my legs seemed anarobic all the time. He had me tested for pad which came back neg. It was the statin causing my problem. I used to run seven miles in 43 minutes, now I use two canes just to be able to walk. Stopped taking this drug four months ago and my lipid panel now reads 140 with my hdl up from 38 to 49. Hopefully sometime in the future I'll get the use of my legs back.

Cowboy Willie

Dave said...

Cowboy Willie, this is a tough post to understand.

"It was the statin causing my problem."

How do you know this? You still use canes, you haven't indicated you feel better, AND your LDL cholesterol marker for something bad happing in your body is worse.

" I used to run seven miles in 43 minutes, now I use two canes just to be able to walk."

How long ago did you stop running? Before or after you started taking statins? And how old are you now? 45? 50? 75?

Anonymous said...

Dr. Mintz,
thank you for your blog. I'd would be interested in your opinion on this article:

http://www.nytimes.com/2012/03/05/opinion/the-diabetes-dilemma-for-statin-users.html?scp=3&sq=statins&st=cse

In this blog:

http://www.proteinpower.com/drmike/statins/statins-and-diabetes/

much is made of an apparently highly cited stude where the authors use p<.05 (!) and single-tailed tests (!)

I don't know much about medicine, but I do know mathematics and this looseness is troubling to say the least.

Thank you.

Bill

Dr. Matthew Mintz said...

anonymous,
thanks for you comments and links.
Dr. Topol's article in the NY Times raised a lot of controversy. (On blogger pointed out that Dr. Topol seems to have changed his mind on statins based on previous statements). It should be noted that in the second link 1) the doctor is clearly against statins and 2) is selling books and nutritional supplements.

It is true that few big studies have shown a mortality benefit from statins. However, showing a mortality benefit is very, very difficult for virtually any medication that is out there. Off the top of my head, smoking cessation is the one thing I can think of where a clear mortality benefit was shown. More recently, colon cancer screening seems to have shown mortality benefit. Notice that neither of these are examples of pills. That being said, there is a substantial amount of data showing that in high risk patients, statins reduce heart attacks and strokes. I don't know if you know of anyone who has had a heart attack or stroke, but I can tell you that quality of life after a heart attack an stroke is substantially affected. Thus, if something substantially reduces heart attacks or strokes, even if it doesn't save lives, this is a pretty big deal. This is why most of the medical community is on board with statin therapy. The real controversy lies with where you draw the line a benefit and high risk. The lower the risk of the patient, the less benefit you see. The Crestor study was controversial, not because of the diabetes caused by the statin, but because in a relatively low risk population, the relative reduction in heart attacks was almost 50%, but the absolute number (number of heart attacks you actually prevented) was not huge.
I think with the newer evidence we have, it seems clear that high potent statins elevate blood glucose a little bit. For those that are pre-diabetic, this will make them officially diabetic by current standards a little bit sooner. However, if a pre-diabetic uses a statin and that statin raises their sugar a bit, it is not likely to be harmful. The impact of raising a patients sugar from 110 to 126 is unclear. However, men who are pre-diabetic have 4x the risk of heart disease and pre-diabetic women have 6x the risk. Thus, in these patient, it is far more likely that the statin helped the patient (prevented a heart attack or stroke) then harmed them (raised their sugar a tiny bit).

Anonymous said...

Dr. Mintz, Are you willing to share YOUR conflicts of interest on this thread? I think to be fair and balanced you should reveal your financial relationship with statin drug companies.

Dave Wyman said...

"quality of life after a heart attack an stroke is substantially affected."

But is it? I've had two heart attacks. The first was mild. The second time was serious, painful, I thought I might die; a clot formed inside a stent - I was left with, according to my Dr., "a little scarring" of my heart.

I've made, twice, full recoveries. I don't hold back when I exercise. At 64, I'm going to ride my bike 100 miles on Saturday.

Isn't this, that you also wrote, more true, Dr. Mitnz:

"The lower the risk of the patient, the less benefit you see."

I've lowered a lot of risks: I eat healthy foods, I exercise a lot, I got rid of the stress that I think caused the first heart attack (two years of personal issues).

My coronary artery plaque consists of, and as of a couple of years ago, some 20% "bumps." Recent ultrasound of my carotid arteries shows they are clear. Without statins, my cholesterol numbers are normal to excellent (LDL about 120). I'm fairly lean. No diabetes, I don't smoke.

So why am I taking a high-dose statin?

I think my cardiologist has put me in a box: prior heart attack, family history = statins. I'm a statistic to him, not an individual patient.

Whereas I think my lifestyle since my heart attack confers plenty of risk reduction, other, than perhaps, the reported stabilization of plaque, without resorting to statins.

On the other hand, I did have a heart attack, and I have a family history of heart disease. And so, when I read back a couple of paragraphs, I think I'm acting like a crazy global warming denier when I question the value of statins.

"the lower the risk of the patient, the less benefit you see."

Dr. Matthew Mintz said...
This comment has been removed by the author.
Dr. Matthew Mintz said...

My conflicts of interests are clearly displayed on my disclosures page. The link is available just below "about Dr. Mintz" and just above the google search box. As an academic physician who has done research in several areas, I am highly sought after by multiple companies in the industry and have advised, consulted and spoked for a variety of companies over the years in several disease states. My primary areas of expertise are respiratory and diabetes. I have not spoken or advised for a company regarding cholesterol drugs in over 2-3 years.

Dr. Matthew Mintz said...

@Dave Wyman,
Your raise an excellent point that all patients are unique. That's part of what is fun about being a physician. If we just did guidele/cookbook medicine, anyone could do this.
When writing a blog with medical information, I have to write in generalizations. Thus, it is generally true that someone who has had two heart attacks is at substantial risk for a 3rd heart attack, and should be treated very aggressively to prevent this, which by most experts would include use of a statin.
However, there are always exceptions. I can not give you specific medical advice on a blog without knowing your complete medical history, but I am very suprised that you had two heart attacks (one if which the cardiologist felt they needed to stent you) but your carotid ultrasounds are clear. This just doesn't make sense. Cardiovascular disease is a systemic process. If you received a stent you should at least have a moderate amount of atherosclerosis in both you coronary arteries (which they would have seen on your angiogram) and your cartoid ultrasound.
Again, I am not giving you specific advice, but rather suggesting your situtation may indeed be unique and once again agreeing with you that every patient needs to be treated individually.

Anonymous said...

Too bad so many physicians have little or no under standing of physiology and therefor are easily brain washed about supposed posative effects of cholesterol promoting plaque build up and the need for statins to destroy cholesterol. Highh cholesterol is not the cause of plaque problems. Any competant cardiac surgeon will tell you that artery cell lining inflamation is the real problem. Destroying cholesterol with statins also destroys CoQ10 promoting stokes and heart attacks. if you take a statin poison, why not take cyanide too?

Anonymous said...

Dr. Mintz,
Maybe someday there will be genetic testing or other screening to determine people who could react very badly to statins (in my case, Simvastatin). I hope you will not prescribe them to anyone who is being seen for unexplained weakness, as I was at the time. Looking back, I was always having some kind of intermittent problem with fatigue over adulthood, even though I was now running personal-best 10k's in my late 40's. Now, 6 years later, I am debating whether to take the ultimate step, which is to go see a mito doctor. The Mito/genetic specialty is the only one that seems to have a handle on permanent statin drug reactions. Most everyone else seems to think they do not exist.

In 2007, after significant prodding by the Dr. for high cholesterol but no inflammation or anything else, I took 10 mg Simvastatin. My muscles started to feel tight and dead when I ran, but I did not connect the dots. After four weeks, my stomach valve quit working at night, and acid began pouring out when I tried to sleep. All kinds of other things broke soon after, resulting in several trips to the emergency room. They got to the end of the differential diagnoses and - you guessed it - "it's in your head". Only after taking the supplements I learned of from fellow sufferers on the spacedoc forums did I start to get to where I could function enough to go back to work six months later. I have to carefully manage energy now, and I am up past $3000/yr of supplements (increasing over time) to be able to function at least enough to hold down a job.

Drug reactions are an interesting statistical theory, unless it happens to you. If you read the forums over on that site, you will see that there is terrible, crushing permanent destruction that happens to people - much more than temporary side effects.

Sorry, I have to be "Anonymous". My name is rare and would come up on a search.

Jared McDade said...

Dr. Mintz,

Concerning balanced opinion, I would feel more confident in your opinions if you had at least read the works of Dr. Graveline and others. As one of those who suffered a minor heart attack and had two stents installed I don't feel that 10% lessening of risk for another heart attack justifieds the reduction in lifestyle that my symptoms of (I feel)statin damage has me living with i.e. leg weakness despite bicycling, back pain, mood change and agression to name a few. I realize that, as a doctor you're busy, but also realize that as a doctor your words carry added weight and I would have more confidence if you expressed youself from having read Graveline's work(s).

Russ Brady