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NewdestinyX

Statins - benefits versus risks

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NewdestinyX

I would like to explore the research available on this topic. Sadly a recent very, very helpful thread on the benefits versus risks of statin got deleted because argumentation ensued over the controversial Dr Bernstein input getting intermixed with the more reliable peer reviewed material.

 

I personally believe this topic needs more investigation and we need as T2 diabetics to share our articles, experiences about this important topic of cholesterol management and if statins are the best approach - based on our experiences and the research out there. I will start with the 'tried and true' position on the issue -- which is that statins, for their use in cholesterol lowering, are an important part of the diabetic's arsenal against heart disease that can be caused my their condition.

 

This study referenced at WebMD, represents new research backing the position. Though funded by AstraZeneca a drug company -- it was peer reviewed as well by the research community.

 

As the original poster I need to ask that all input from Dr Bernstein's website and quotations from his book and be disallowed in this thread. It gets too heated because it opens up other diet philosophy controversies. And Bernstein's input has been represented in MANY, MANY threads to date.

 

And I'm interested only in peer reviewed studies as well not Internet opinion pieces. If a study isn't referenced -- then don't post here, please. In this article inflammation seems to be the main key in CVD but its link with high cholesterol is undeniable.

Statin Benefits Patients With Low Cholesterol

Crestor Users Cut Cardiac Deaths in Half

By Salynn Boyles

WebMD Health News

Reviewed by Elizabeth Klodas, MD, FACC

 

Nov. 10, 2008 -- Millions of Americans take statins to lower their cholesterol, but dramatic findings from a study of the statin drug Crestor suggest that millions more might benefit from treatment.

 

The findings may also lead to a more important role for the blood test high-sensitivity C-reactive protein (hsCRP) in assessing cardiovascular risk.

Related Medications

 

More information on common Cholesterol drugs from RxList:

* Vytorin

* Lipitor

* Zetia

The study included about 18,000 apparently healthy men and women with normal cholesterol but higher than normal levels of high sensitivity C-reactive protein, a marker of inflammation that has been linked to heart disease.

 

Originally planned as a four-year trial, the study was stopped late in March after most participants had taken the statin for less than two years.

 

People who took Crestor had half as many major cardiovascular events as people assigned to the placebo arm of the trial.

 

The study was funded by Astra-Zeneca, which makes Crestor. It was presented in New Orleans at the American Heart Association's Scientific Sessions and it also appears in the Nov. 20 issue of The New England Journal of Medicine.

 

"Physicians can no longer assume that a patient with low cholesterol has a low risk for a heart attack or stroke," lead researcher Paul M. Ridker, MD, of Boston's Brigham and Women's Hospital, tells WebMD.

Statins Benefit "Low-Risk" Patients

 

Statins are generally prescribed only for people with high cholesterol or those who have borderline high cholesterol and other risk factors for heart attack and stroke, such as diabetes or established heart disease.

 

But as many as half of all heart attacks and strokes occur among people without these risk factors who have LDL cholesterol levels that are below recommended thresholds for statin treatment.

 

The newly reported trial was designed to explore whether statins might also benefit these people.

 

All of the study participants had LDL cholesterol levels of less than 130 milligrams per deciliter when they entered the trial, and none had known diabetes or heart disease. But they did have high-sensitivity CRP levels of 2.0 milligrams per liter or higher.

 

Blood hsCRP levels of less than 1 milligram per liter are indicative of low cardiovascular risk, while 1 to 3 milligrams per liter indicates moderate risk, and greater than 3 indicates high risk, Ridker says.

 

About 9,000 study participants were treated with 20 milligrams per day of Crestor and an equal number of participants took a placebo.

 

When the trial was stopped after a median follow-up of 1.9 years, statin users had lowered their LDL cholesterol by an average of 50% and their hsCRP by 37%.

 

There were also half as many heart attacks, strokes, and deaths from cardiovascular causes among the participants taking the statin. In all, 0.9% of statin users had one of these events, compared to 1.8% of placebo users.

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Subby

Interesting article. As a type 1 with an established equal if not a great deal more risk in these areas for the same reasons, I hope I am not out of place making a comment on this thread.

 

I'm up in the air about statins personally, I've tried a few for some times, but as they give me unpleasant short term effects, I'm giving them a rest for the moment.

 

What was interesting was that despite the tone of the article, the actual difference statins made seemed quite small to me:

 

There were also half as many heart attacks, strokes, and deaths from cardiovascular causes among the participants taking the statin. In all, 0.9% of statin users had one of these events, compared to 1.8% of placebo users.

 

Put into literal terms, it seems that approximately 85 statin takers had these events, out of 9,000, compared to approximately 160 placebo takers out of 9,000.

 

(someone why is better at maths is welcome to correct those rough figures).

 

So, in effect around a 1% improvement in outcome on statins vs off? That doesn't seem nearly as dramatic as the report made it out to be. I would have thought that such small numbers really tended to exclude the usefullness or accuracy of percentage comparisons - but I do not know for sure.

 

I do think it's only fair, if you are going to exclude non-peer referenced etc materials, to also have very clear disclosure policy. In this case, the makers of Crestor ran the study. It was quoted, but I mention it again to be clear.

 

Two further quotes from the article, also have bearing on this report and discussion, it's interesting to what the actual study publishers think about the study.

 

In an editorial published with the study, Hlatky wrote that it is still not clear if the benefits of treating relatively low-risk people with statins for many decades outweigh the risks.

 

"We are talking about treating relatively low-risk people with a drug that they will take for the rest of their lives," he tells WebMD. "We can't just say everyone should be treated. Individual risk factors need to be considered."

 

In conclusion to my post, I'm pointing out things I think are important to realise about this study in their comment about the benefits vs risks - suitably within bounds of the conversation you were asking for, I hope. I don't really have any agenda to discredit or support statins. I hope and wish statins work well, I sure wish it was an easier decision to make, especially given those short term issues I get taking them (heart palpitations, or liver area pains). If there was very clear, data directly showing statins substantially improve CVD risks (not cholesterol, they sure do that for me), then I would feel more comfortable or justified trying to ride out those other effects. I still haven't seen strong evidence from a study, and from my reading this study is unfortunately no exception. Interested in more findings.

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Josselyn

I've not yet taken statins. I have grave misgivings about them. I investigate them here and via Google. As a result, this thread has drawn my interest...and I have no idea where Dr. B stands on it, but I can hazard a guess...and will later peek elsewhere to find out.

 

My MD will push for statins next visit (end of January) if my cholesterol levels haven't dropped. They'd risen from a 213 at the beginning of this D trip six months ago, to a 263 two months ago (two different labs, though)...despite serious weight loss from lower carbing it. MD chalked it up to a flux in weight/diet for the time being, but mentioned statins.

My trigs are ok...an improvement.

 

I just don't want to take more meds...especially if not needed.

I'm just not a med kind of gal, and having D is forcing me to change that. I hate it.

 

This is an interesting topic, Grant.

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NewdestinyX
Interesting article. As a type 1 with an established equal if not a great deal more risk in these areas for the same reasons, I hope I am not out of place making a comment on this thread.
-NOT AT ALL. Please participate.

 

In conclusion to my post, I'm pointing out things I think are important to realise about this study in their comment about the benefits vs risks - suitably within bounds of the conversation you were asking for, I hope. I don't really have any agenda to discredit or support statins. I hope and wish statins work well, I sure wish it was an easier decision to make, especially given those short term issues I get taking them (heart palpitations, or liver area pains). If there was very clear, data directly showing statins substantially improve CVD risks (not cholesterol, they sure do that for me), then I would feel more comfortable or justified trying to ride out those other effects. I still haven't seen strong evidence from a study, and from my reading this study is unfortunately no exception. Interested in more findings.
I noted all the same caveats you pointed out. And for future posts -- a sponsored study is fine here as long as it is peer reviewed by someone NOT in the study or receiving funding from the sponsor.

 

Now even having said that -- it is harder to find the peer reviewed status of a given article -- so let's just 'post' what we find but be open to each other being 'hard on the sources' if a peer review isn't evident in the article. That's why I used this study first. It had both peer review but also was funded by a drug company. That's fine. The only contributor I don't want cited here is Dr. L. Bernstein.

 

Thanks, Subby!

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NewdestinyX
I've not yet taken statins. I have grave misgivings about them.
So do I.

 

My MD will push for statins next visit (end of January) if my cholesterol levels haven't dropped.
Mine already has - as a preventative measure and my LDL is only'118'!!!, HDL 48 and Trigs only 83. 3.9% ratio. I think he's being 'overprotective'. But I understand why he wants it based on what I read. And all this new research that I hope SHottleBop and Frank will repost has me really wondering, if LDL is the main issue or if it's more about inflammation only and.. well so much more.
I just don't want to take more meds...especially if not needed.

I'm just not a med kind of gal, and having D is forcing me to change that. I hate it.

I'm with you here, Josselyn. I have hated meds all my life. Thankfully the Walmart near me just changed to a different manufacturer for their METFORMIN 500's which now have a nice tapered edge and have a slipperier formulation on the coating of the pill. SO, SO much easier to swallow now than the APOTEX brand -- which is a very 'fat' (tall) pill with a regular rough aspirin-like coating. I choked on them at least once a day.
This is an interesting topic, Grant.
For me too.. hopefully we can get even better educated.

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NewdestinyX

I find THIS ARTICLE interesting in that the chart shows that the 'optimum' LDL number gets lower with the higher risk factors you have -- like CVD in family history and Diabetes. The 'under' 100 numbers is only for the 'highest risk' people. People with low risk need only a 160. That supports the notion I also read that higher LDL cholesterol is very helpful in other areas of good health.

 

How Is High Blood Cholesterol Treated?

 

The main goal of cholesterol-lowering treatment is to lower your low-density lipoprotein (LDL) level enough to reduce your risk for having a heart attack or diseases caused by hardening of the arteries. In general, the higher your LDL level and the more risk factors you have, the greater your chances of developing heart disease or having a heart attack. (A risk factor is a condition that increases your chance of getting a disease.)

 

Some people are at high risk for heart attack because they already have heart disease. Other people are at high risk for developing heart disease because they have diabetes or a combination of risk factors for heart disease. Follow the steps below to find out your risk for getting heart disease. Talk with your doctor about lowering your risk.

 

Check the list to see how many of the risk factors you have. These are the risk factors that affect your LDL goal:

 

* Cigarette smoking

* High blood pressure (140/90 mg/dL or higher), or if you are on blood pressure medicine

* Low high-density lipoprotein (HDL) cholesterol (less than 40 mg/dL)1

* Family history of early heart disease (heart disease in father or brother before age 55; heart disease in mother or sister before age 65)

* Age (men 45 years or older; women 55 years or older)

 

If you have two or more of the risk factors in the list above, use the NHLBI 10-Year Risk Calculator to find your risk score. Risk scores refer to the chance of having a heart attack in the next 10 years, given as a percentage.

 

Use your medical history, number of risk factors, and risk score to find your risk for developing heart disease or having a heart attack according to the table below.

If You Have___________________________________| You Are in Category_| And Your LDL Goal Is:

Heart disease, diabetes, or a risk score higher than 20% | I. High risk__________| Less than 100 mg/dL*

Two or more risk factors and a risk score 10–20%______| II. Moderately high risk | Less than 130 mg/dL

Two or more risk factors and a risk score lower than 10% | III. Moderate risk_____| Less than 130 mg/dL

One or no risk factors_____________________________| IV. Low to moderate risk | Less than 160 mg/dL

 

*Some people in this category are at very high risk because they have just had a heart attack or because they have a combination of heart disease together with diabetes, risk factors that are severe, or metabolic syndrome. If you are at very high risk, your doctor may set your LDL goal even lower, to less than 70 mg/dL. Your doctor may also set the LDL goal at this lower level if you have heart disease alone.


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ShottleBop

Anyone interested in the risks vs benefits of statins should consider checking out the website of the UCSD Statin Effects Study, which has been commissioned by the National Institutes of Health to collect and report information regarding statin side effects, and which has, itself, extensively reviewed the published literature.

 

There are many, many studies out there, not all of which are available in more than abstract form (which can be spun to reflect the biases of the entity that funded the study). There are, however, folks who have reviewed the extant studies--not just the abstracts, but the underlying data. Many of the authors provide footnotes that point you to the studies that they have reviewed. In deference to the request made in the opening post, I will not list them here, but am happy to make recommendations in response to requests by PM.

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Hammer

I thought that what was posted in the other statin thread, more or less answered the question. From what I read in the other thread, LDL cholesterol has no bearing on heart attacks, and that it was now understood that it's the inflammation of the arteries that was the problem. Once you have inflammation, the LDL cholesterol does it's job of depositing plaque over the inflamed area to protect it. It's this buildup of plaque that eventually causes a heart attack.

 

Statins lower LDL cholesterol, but they also reduce the inflammation of the artery. It's this reduction in the inflammation that is what lowers the risk of heart attacks, so why lower the LDL cholesterol and suffer all of the bad side effects that come from lowered LDL levels, when all that's really needed is to reduce the inflammation?

 

Didn't the drug companies who make statins, jump on the new bandwagon of promoting their already tired usage of statins to now say that they reduce the inflammation, and thereby reduce heart attacks?

 

I'm just repeating what was discussed in the other thread, so I don't remember the sources, but isn't that what came out of the other thread? Did I misunderstand the info in the other thread making everything I just said above wrong?:confused:

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ShottleBop

You are right, Hammer, in that those who have reviewed all of the extant studies--underlying data as well as abstracts--have found that the benefits that statins confer is independent of their effect on the level of LDL in our bloodstreams.

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ShottleBop
In conclusion to my post, I'm pointing out things I think are important to realise about this study in their comment about the benefits vs risks - suitably within bounds of the conversation you were asking for, I hope. I don't really have any agenda to discredit or support statins. I hope and wish statins work well, I sure wish it was an easier decision to make, especially given those short term issues I get taking them (heart palpitations, or liver area pains). If there was very clear, data directly showing statins substantially improve CVD risks (not cholesterol, they sure do that for me), then I would feel more comfortable or justified trying to ride out those other effects. I still haven't seen strong evidence from a study, and from my reading this study is unfortunately no exception. Interested in more findings.

 

Subby, you might find Jay Cohen's book (What You Must Know About Statin Drugs & Their Natural Alternatives) helpful. He takes a very balanced view towards statins--he is definitely not anti-statin, just someone who is also cognizant of their risk. He says that the most common side effects, such as muscle pain, are dose-related, and can be ameliorated by reducing the dosage to the smallest amount necessary to achieve the desired effect. (Even Dr. Graveline, who created spacedoc.net to make people aware of the risks posed by the use of statins, believes that they have their place, at a very low dose, as anti-inflammatory agents.)

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MrsMia

ShottleBop,

 

It's my understanding that statins have been prescribed by so many doctors because they've been convinced that the lipid hypothesis somehow became a fact instead of a hypothesis. With no way of determining if somebody who has not had a previous cardiac event actually has heart disease without a ct scan of the heart and arteries itself to check for arteries that are diseased, then why are they prescribing statins? As Dr. Eades has stated, and I am paraphrasing him, 'doctors are supposed to treat diseases not numbers.' Basically doctors are treating high cholesterol numbers and not heart disease without specific testing. Have your read something like this too as I think we both read a lot of the same sources.

 

I think I'll keep that in mind when it comes to statins. Still being a hypothesis will definitely make me stay away from them for the time being.

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70sFan77

Can statins cause increased blood sugar and dizziness? I asked this question in the thread that was deleted before I could check for replies.

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ShottleBop

This commentary was published in 2007, in "The Lancet." It was written by J Abramson, Harvard Medical School, Cambridge, Massachusetts, USA (JA); and J M Wright, Department of Anesthesiology, Pharmacology & Therapeutics and Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 (JMW). It is called: Are Lipid lowering (Statins) Guidelines Evidence-Based? Excerpt (emphasis added):

 

The last major revision of the US guidelines, in 2001,1 increased the number of Americans for whom statins are recommended from 13 million to 36 million, most of whom do not yet have but are estimated to be at moderately elevated risk of developing coronary heart disease.2 In support of statin therapy for the primary prevention of this disease in women and people aged over 65 years, the guidelines cite seven and nine randomised trials, respectively. Yet not one of the studies provides such evidence.

 

For adults aged between 30 and 80 years old who already have occlusive vascular disease, statins confer a total and cardiovascular mortality benefit and are not controversial. The controversy involves this question: which people without evident occlusive vascular disease (true primary prevention) should be offered statins? With about three-quarters of those taking statins in this category,3 the answer has huge economic and health implications. In formulating recommendations for primary prevention, why do authors of guidelines not rely on the data that already exist from the primary prevention trials?

 

We have pooled the data from all eight randomised trials that compared statins with placebo in primary prevention populations at increased risk.4 Unfortunately, our analysis is imperfect because these trials are not solely primary prevention: 8.5% of patients had occlusive vascular disease at baseline.5 We used two outcomes to estimate overall benefi t (benefi t minus harm): total mortality and total serious adverse events (SAEs). Total mortality was not reduced by statins (relative risk 0.95, 95% CI 0.89-1.01).

In the two trials that reported total SAEs, such events were not reduced by statins (1.01, 0.97-1.05) (data on SAEs from the other trials were not reported).

 

The frequency of cardiovascular events, a less encompassing outcome, was reduced by statins (relative risk 0.82, 0.77-0.87). However, the absolute risk reduction of 1.5% is small and means that 67 people have to be treated for 5 years to prevent one such event. Further analysis revealed that the benefi t might be limited to high-risk men aged 30-69 years. Statins did not reduce total coronary heart disease events in 10 990 women in these primary prevention trials (relative risk 0.98, 0.85-1.12).6 Similarly, in 3239 men and women older than 69 years, statins did not reduce total cardiovascular events (relative risk 0.94, 0.77-1.15).7

 

Our analysis suggests that lipid-lowering statins should not be prescribed for true primary prevention in women of any age or for men older than 69 years. High-risk men aged 30-69 years should be advised that about 50 patients need to be treated for 5 years to prevent one event. In our experience, many men presented with this evidence do not choose to take a statin, especially when informed of the potential benefits of lifestyle

modification on cardiovascular risk and overall health.8

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ShottleBop
Can statins cause increased blood sugar and dizziness? I asked this question in the thread that was deleted before I could check for replies.

 

Sorry, 70sFan77, but I haven't seen a whole lot on this issue, myself, other than that, in at least one statin trial, the number of cases of diabetes cases in the treated group increased slightly, albeit by an amount that was statistically insignificant. I suggest you poke around with Google, yourself.

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xMenace

I would Like to know why these side effects exist. Is it because of the drug interaction or because of the reduction in cholesterol levels. I don't really know.

 

If it's because cholesterol is reduced to a dangerous level, I think low carbers may be unknowingly at risk do to possible inflated LDL values because of innacuracies in the Friedwald formula when triglycerides are very low. There doesn't seem to be any clear answers to this question which makes me lean towards teh lowering of cholesterol theory. Scientific Community: I'd like some clear answers please!

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ShottleBop

Low LDL is associated with increased mortality in patients admitted with heart attacks. This article appeared in: Cardiol J. 2009;16(3):227-33. ("Low admission LDL-cholesterol is associated with increased 3-year all-cause mortality in patients with non ST segment elevation myocardial infarction."; Al-Mallah MH, Hatahet H, Cavalcante JL, Khanal S.; Division of Cardiology, Henry Ford Heart and Vascular Institute, Detroit, MI 48202, USA. malmall1@hfhs.org)

 

Abstract:

BACKGROUND: The relationship between admission low-density lipoprotein (LDL) levels and long-term outcomes has not been established in patients with acute coronary syndrome. We tested the hypothesis that patients who develop non-ST segment elevation myocardial infarction (NSTEMI) despite low LDL have a worse cardiovascular outcome in the long term.

 

METHODS: Patients admitted with NSTEMI between 1 January 1997 and 31 December 2000 and with fasting lipid profiles measured within 24 hours of admission were selected for analysis. Baseline characteristics and 3-year all-cause mortality were compared between the patients with LDL above and below the median. Multivariate analysis was used to determine the predictors of all-cause mortality, and adjusted survival was analyzed using the Cox proportional hazard model. RESULTS: Of the total of 517 patients, 264 had LDL <or= 105 mg/dL and 253 had LDL > 105 mg/dL. There was no difference in age, gender, severity of coronary artery disease, and left ventricular ejection fraction between the 2 groups. Thirty-six percent of patients with LDL <or= 105 mg/dL and 24% of patients with LDL > 105 mg/dL were on lipid-lowering therapy on admission. After 3 years, patients with admission LDL <or= 105 mg/dL had higher all-cause mortality rate compared to patients with LDL > 105 mg/dL (14.8% vs. 7.1%, p = 0.005). The higher all-cause mortality persisted (OR 1.8, 95% CI 1.0-3.5, p = 0.05) even after adjustment for confounding variables.

 

CONCLUSIONS: In our cohort, lower LDL-cholesterol at admission was associated with decreased 3-year survival in patients with NSTEMI. Whether this was a result of current therapy or a marker for worse baseline characteristics needs to be studied further.

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ShottleBop
I would Like to know why these side effects exist. Is it because of the drug interaction or because of the reduction in cholesterol levels. I don't really know.

 

If it's because cholesterol is reduced to a dangerous level, I think low carbers may be unknowingly at risk do to possible inflated LDL values because of innacuracies in the Friedwald formula when triglycerides are very low. There doesn't seem to be any clear answers to this question which makes me lean towards teh lowering of cholesterol theory. Scientific Community: I'd like some clear answers please!

 

Statins reduce cholesterol by interfering with its production. They inhibit a reaction far down the chain in the "mevalonate pathway," and prevent the production of several other substances that are critical to our metabolic processes. I can suggest a few sites with the information, if you'd like. Just send me a PM.

 

"Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism", published in

American Journal of Cardiovascular Drugs:

1 November 2008 - Volume 8 - Issue 6 - pp 373-418

doi: 10.2165/0129784-200808060-00004

 

Abstract:

HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications, have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many nonmuscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity.

 

There are other studies that indicate that low cholesterol itself may be an issue.

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CALynn

As someone who failed 4 different statins with myositis and myopathy, driving towards rhabdomyolysis, this is a topic I'm interested in.

 

Statin Associated Rhabdomyolysis

 

Statins & Associated Rhabdomyolysis

 

"Though tolerated well by the great majority of statin users, rhabdomyolysis has proven to be a very significant side effect. This condition is due to extreme muscle cell inflammation with rupture of the cell wall, spillage of cellular contents into the blood stream and secondary renal tubule obstruction."

 

"Some feel this process is related to excess coenzyme Q10 inhibition fostering loss of cell wall integrity. Others show research findings suggesting that cholesterol insufficiency within the muscle cells leading to altered cell signaling is the dominant factor. Still others feel that unrecognized predisposing genetic factors are contributing."

 

"Starting historically, from the period October 1997 to December 2000, 772 cases of statin associated rhabdomyolysis were reported to the FDA. Of this number 387 or 50% of these cases were associated with the use of Baycol, a relative newcomer at the time. During this same time period, 72 deaths resulted from rhabdomyolysis.

These observations prompted the consideration of withdrawing Baycol from the market. However, by the time action was finally taken, seven months later, in August 2001, Baycol was found to be associated with approximately 100 rhabdomyolysis deaths."

 

"The withdrawal of Baycol by no means eliminated the statin associated rhabdomyolysis problem, for all statin drugs share this tendency, especially Zocor and Lipitor. Of the 772 hospitalizations during this time period, 24% were associated with the use of Zocor and 11% with the use of Lipitor. Although the concomitant use of fibrates has been a factor with many of the rhabdomyolysis cases, especially with Baycol, this effect is considered to be somewhat additive only without changing the statin drug tendency in this regard. "

 

"Further review of the FDA results reveal that of the total number of rhabdomyolysis cases reported in their database, 42.7% were found to be statin associated cases, representing a near sevenfold over-representation of statin use among the total cases, strongly supporting the causal role of these drugs. I recently found an article written by a medical doctor stating unequivocally that the statin effect on rhabdomyolysis was about the same as the normal, non-statin incidence. Nothing could be further from the truth.

 

The overall reported incidence of fatal rhabdomyolysis, excluding Baycol, was felt to be close to 0.15 deaths per one million prescriptions for the other statins commonly used. Following Baycol's withdrawal in 2001, this rate of fatal cases, associated primarily with the use of Zocor, Lipitor and Pravachol, continued unchanged until the arrival in 2003 of Crestor."

 

"In October 2003, this powerful new statin drug was approved for marketing after a somewhat stormy approval period during which time its highest strength (80mg) pill was withdrawn because of the several cases of rhabdomyolysis seen and reported during the clinical phase of Crestor evaluation. Troubles were just beginning for this newcomer to the incredibly profitable statin market. The FDA soon learned that Crestor had a unique renal toxicity problem independent of an obvious rhabdomyolysis problem from the very beginning. The new data comparisons showed that the rate of acute renal failure reports in people not having rhabdomyolysis was 75 times higher for Crestor than for the other statins combined.

 

In addition during the period from October 1, 2003 through September 30, 2004, it was found that the rate of reports of rhabdomyolysis sent to FDA was 6.2 times higher than the rate for all of the other statins combined. This is separate from the specific renal toxicity mentioned above."

 

"Physicians must also understand that just behind Crestor in rhabdomyolysis potential is Zocor, now masquerading as Vytorin, accounting for close to 25% of rhabdomyolysis deaths. Lipitor is just as powerful as Zocor but only half as likely to cause rhabdomyolysis. Please take heed. If you think your drug reps are going to tell you any of this you are naïve and if you think you can research it out for yourself, be prepared for many hours of toil."

 

Duane Graveline MD MPH

Former USAF Flight Surgeon

Former NASA Astronaut

Retired Family Doctor

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CALynn

JAMA -- File Not Found

 

289/13/1681

JAMA

 

CLINICIAN'S CORNER

 

Statin-Associated Myopathy

 

Paul D. Thompson, MD; Priscilla Clarkson, PhD; Richard H. Karas, MD, PhD

 

JAMA. 2003;289:1681-1690.

 

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are associated with skeletal muscle complaints, including clinically important myositis and rhabdomyolysis, mild serum creatine kinase (CK) elevations, myalgia with and without elevated CK levels, muscle weakness, muscle cramps, and persistent myalgia and CK elevations after statin withdrawal. We performed a literature review to provide a clinical summary of statin-associated myopathy and discuss possible mediating mechanisms. We also update the US Food and Drug Administration (FDA) reports on statin-associated rhabdomyolysis. Articles on statin myopathy were identified via a PubMed search through November 2002 and articles on statin clinical trials, case series, and review articles were identified via a PubMed search through January 2003. Adverse event reports of statin-associated rhabdomyolysis were also collected from the FDA MEDWATCH database. The literature review found that reports of muscle problems during statin clinical trials are extremely rare. The FDA MEDWATCH Reporting System lists 3339 cases of statin-associated rhabdomyolysis reported between January 1, 1990, and March 31, 2002. Cerivastatin was the most commonly implicated statin. Few data are available regarding the frequency of less-serious events such as muscle pain and weakness, which may affect 1% to 5% of patients. The risk of rhabdomyolysis and other adverse effects with statin use can be exacerbated by several factors, including compromised hepatic and renal function, hypothyroidism, diabetes, and concomitant medications. Medications such as the fibrate gemfibrozil alter statin metabolism and increase statin plasma concentration. How statins injure skeletal muscle is not clear, although recent evidence suggests that statins reduce the production of small regulatory proteins that are important for myocyte maintenance.

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CALynn

Clinical perspectives of statin-induced rhabdomyol... [Am J Med. 2006] - PubMed result

 

Am J Med. 2006 May;119(5):400-9.

 

Clinical perspectives of statin-induced rhabdomyolysis.

 

Antons KA, Williams CD, Baker SK, Phillips PS.

Scripps Mercy Clinical Research Center, Scripps Mercy Hospital, San Diego, Calif 92103, USA.

 

Fear of muscle toxicity remains a major reason that patients with hyperlipidemia are undertreated. Recent evaluations of statin-induced rhabdomyolysis offer new insights on the clinical management of both muscle symptoms and hyperlipidemia after rhabdomyolysis. The incidence of statin-induced rhabdomyolysis is higher in practice than in controlled trials in which high-risk subjects are excluded. Accepted risks include age; renal, hepatic, and thyroid dysfunction; and hypertriglyceridemia. New findings suggest that exercise, Asian race, and perioperative status also may increase the risk of statin muscle toxicity. The proposed causes and the relationship of drug levels to statin rhabdomyolysis are briefly reviewed along with the problems with the pharmacokinetic theory. Data suggesting that patients with certain metabolic abnormalities are predisposed to statin rhabdomyolysis are presented. The evaluation and treatment of patients' muscle symptoms and hyperlipidemia after statin rhabdomyolysis are presented. Patients whose symptoms are related to other disorders need to be identified. Lipid management of those whose symptoms are statin-related is reviewed including treatment suggestions.

PMID: 16651050 [PubMed - indexed for MEDLINE]

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CALynn

Rhabdomyolysis due to the additive effect of statin therapy and hypothyroidism: a case report

J Med Case Reports. 2007; 1: 130.

 

Published online 2007 November 10. doi: 10.1186/1752-1947-1-130. PMCID: PMC2170445

 

Copyright © 2007 Yeter et al; licensee BioMed Central Ltd.

 

Rhabdomyolysis due to the additive effect of statin therapy and hypothyroidism: a case reportEkrem Yeter, 1 Telat Keles,1 Tahir Durmaz,1 and Engin Bozkurt1

 

1Department of Cardiology, Ataturk Education and Research Hospital, Ankara, Turkey

 

Corresponding author.

Ekrem Yeter: ekremyeter@hotmail.com ; Telat Keles: telatkeles@hotmail.com ; Tahir Durmaz: drtdurmaz@hotmail.com ; Engin Bozkurt: ebozkurt@atauni.edu.tr

 

Received March 7, 2007; Accepted November 10, 2007.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License

(http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

 

Abstract

 

We describe a patient with previously undiagnosed hypothyroidism who developed rhabdomyolysis while taking a statin. He had no other precipitating factors. The statin was stopped, intravenous fluids were started immediately and L-thyroxin was given after confirming the diagnosis of hypothyroidism. His symptoms improved over a few days. Because rhabdomyolysis is a rare but potentially life threatening disorder when complicated by acute tubular necrosis and renal failure, physicians must pay special attention when starting statins in patients with hyperlipidemia.

 

 

Introduction

 

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been widely used as the first choice for treatment of hyperlipidemia. Side effects of statins are relatively infrequent [1]. The most common side effects are skeletal muscle complaints, including clinically important myositis and rhabdomyolysis, mild serum creatine kinase (CK) elevations, myalgia with or without elevated CK, muscle weakness, muscle cramps, and persistent myalgia [2]. The risk of rhabdomyolysis and other adverse effects with statin use can be exacerbated by several factors, including compromised hepatic and renal function, hypothyroidism, diabetes, and concomitant medications [2]. Herein, we report a case of rhabdomyolysis due to atorvastatin in a patient without any precipitating factors other than hypothyroidism.

 

Case presentation

 

A 56-year-old man was admitted to hospital with complaints of a two week history of severe myalgia and proximal muscle weakness of the extremities, with difficulty in exercise and climbing stairs. He denied vigorous physical exercise and alcohol use. His medications consisted of ramipril for hypertension and atorvastatin for hyperlipidemia which he had taken for the previous two weeks. He had no familial or prior personal history of thyroid disease or muscle disorders. He had no previous history of muscular toxicity with statin or fibrate use.

On physical examination, he was afebrile, had periorbital puffiness, lip swelling and mild diffuse goitre, normal heart rate (89 beats/min). All the limbs were swollen and he had pitting edema. Other systems were normal.

 

On admission, laboratory measurements revealed: hemoglobin 11.3 g/dl, total leucocyte count 7.7 × 109/l, serum K 3,9 mEq/l, Na 137 mEq/l, urea 34 mg/dl, creatinine 1,4 mg/dl blood glucose 85 mg/dl. Serum muscle enzymes were markedly elevated: CK 3471 IU/l (normal up to 170), CK-MB 90 IU/l (normal up to 15), LDH 730 IU/l (150–500), Aspartate transaminase (AST) 91 IU/l, alanine transaminase (ALT) 50 IU/l. Urine analysis showed moderate blood on dipstick, but on microscopic examination there were no erythrocytes. Therefore, we assumed that this was due to myoglobulinuria. Thyroid function tests confirmed the diagnosis of hypothyroidism: thyroid stimulating hormone (TSH) >75 uIU/ml (0.4–4), free T3 (FT3) 0.85 pg/ml (1.57–4.71), free T4 (FT4) 0.3 pg/dl (0,85–1,78). The diagnosis was rhabdomyolysis secondary to the additive effect of hypothyroidism and atorvastatin. Atorvastatin was stopped, intravenous fluids were started immediately and L-thyroxin (100 μg/day) was given after confirming the diagnosis of hypothyroidism. His symptoms progressively improved in a few days. On discharge, two week after admission, serum CK, AST and ALT measurements had decreased to 668 IU/l, 23 IU/l, and 27 IU/l respectively. TSH level was in the normal range 6 weeks after starting treatment.

 

Discussion

 

The report describes a patient with rhabdomyolysis due to the additive effect of undiagnosed hypothyroidism and atorvastatin. Statins have been found to be effective in primary prevention as well as secondary prevention of coronary disease [3]. Although statins are well tolerated by most of the patients, they may cause myopathy, rhabdomyolysis and elevated liver enzymes [4].

 

Medications that inhibit cytochrome P-450 (CYP) 3A4, such as macrolide antibiotics, antifungals, and cyclosporine, increase serum concentrations of statins and the risk of rhabdomyolysis [2]. There have been several case reports of rhabdomyolysis induced by hypothyroidism [5] but most of the reported cases were precipitated by exercise [6]. In a previous report, 11.7% of patients with primary hypothyroidism accidentally received statins without having the diagnosis of hypothyroidism. Severity of hypothyroidism might be partially associated with elevation of CK. Statins might be a risk factor for severe myopathy and rhabdomyolysis in patients with hypothyroidism [1].

 

Conclusion

 

We wish to alert the physicians to the importance of early recognition and treatment of hypothyroidism before starting statins, which is essential in reducing risk of mortality and complications from rhabdomyolysis. Screening thyroid function before starting statins is important to avoid rare but serious complications.

 

Competing interests

The author(s) declare that they have no competing interests.

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CALynn

FDA adverse event reports on statin-associated rhabdomyolysis -- Omar and Wilson 36 (2): 288 -- The Annals of Pharmacotherapy

 

The Annals of Pharmacotherapy: Vol. 36, No. 2, pp. 288-295. DOI 10.1345/aph.1A289

 

© 2002 Harvey Whitney Books Company.

 

FDA adverse event reports on statin-associated rhabdomyolysis

 

MA Omar and JP Wilson

 

OBJECTIVE: To determine the number of cases of statin-associated rhabdomyolysis reported to the Food and Drug Administration for 6 statins and to profile the cases.

 

METHODS: A retrospective analysis of all domestic and foreign reports of statin-associated rhabdomyolysis between November 1997 and March 2000 was conducted. Outcome measures included the total number of reports (initial plus follow-up), the number of unique cases, age, gender, percentages of report codes and role codes, and frequencies of concomitant interacting drugs that may have precipitated rhabdomyolysis, outcomes codes, and report source codes.

 

RESULTS: There were 871 reports of statin-associated rhabdomyolysis in the 29-month time frame examined, representing 601 cases. The following number of cases were associated with each of the individual statins: simvastatin, 215 (35.8%); cerivastatin, 192 (31.9%); atorvastatin, 73 (12.2%); pravastatin, 71 (11.8%); lovastatin, 40 (6.7%); and fluvastatin, 10 (1.7%). Drugs that may have interacted with the statins were present in the following number of cases: mibefradil (n = 99), fibrates (n = 80), cyclosporine (n = 51), macrolide antibiotics (n = 42), warfarin (n = 33), digoxin (n = 26), and azole antifungals (n = 12). The reports of 62.1% of cases were classified as expedited. Statins were designated as the primary suspect in 72.0% of the cases. Death was listed as the outcome in 38 cases. The majority of reports (n = 556) were from health professionals.

 

CONCLUSIONS: Compared with the other statins, simvastatin and cerivastatin were implicated in a relatively higher number of reports. Because of the various limitations of a spontaneous reporting-system database, caution is urged when interpreting the relative number of cases reported.

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CALynn

http://www.ncbi.nlm.nih.gov/pubmed/11978159?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA&linkpos=3&log$=relatedarticles&logdbfrom=pubmed

 

Ann Pharmacother. 2002 May;36(5):820-3.

 

Rhabdomyolysis after concomitant use of cyclosporine, simvastatin, gemfibrozil, and itraconazole.

Maxa JL, Melton LB, Ogu CC, Sills MN, Limanni A.

Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246-2088, USA. janma@bhcs.com

 

OBJECTIVE: To report a case of rhabdomyolysis in a patient receiving cyclosporine, simvastatin, gemfibrozil, and itraconazole.

 

CASE REPORT: Rhabdomyolysis occurring in transplant patients receiving both cyclosporine and the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin has been well documented. The exact mechanism by which this interaction leads to rhabdomyolysis is unknown. Experience with newer agents of the statin drug class in transplant patients is limited. Since the interaction between cyclosporine and HMG-CoA reductase inhibitors involves the CYP3A4 enzyme system, the possibility of amplifying this interaction exists when other drugs affecting the same enzyme system are coprescribed. We describe a case in which a heart transplant recipient stable on a drug regimen that included cyclosporine, simvastatin, and gemfibrozil developed rhabdomyolysis after initiation of the antifungal agent itraconazole.

 

DISCUSSION: Drug-drug interactions due to shared metabolism via the CYP3A4 pathway can result in significant adverse outcomes. This article discusses concurrent use of an HMG-CoA reductase inhibitor with other drugs that inhibit the CYP3A4 isoenzyme, leading to a case of possible fatal rhabdomyolysis.

 

CONCLUSIONS: Clinicians must be aware of drugs metabolized via cytochrome P450 isoenzymes and identify those requiring risk-versus-benefit analysis before prescribing. Patients need to be educated as to signs and symptoms requiring immediate physician intervention.

PMID: 11978159 [PubMed - indexed for MEDLINE]

 

 

Note by CALynn: You would be wise to check your meds and determine if any are in the P450 or CYP3A4 groups. This information can be found at:

 

http://medicine.iupui.edu/clinpharm/ddis/table.asp

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bunbury

For those of us, like me, who did not know what Rhabdomyolysis was:

 

Rhabdomyolysis is the rapid breakdown (lysis) of skeletal muscle (rhabdomyo) due to injury to muscle tissue. The muscle damage may be caused by physical (e.g., crush injury), chemical, or biological factors. The destruction of the muscle leads to the release of the breakdown products of damaged muscle cells into the bloodstream; some of these, such as myoglobin (a protein), are harmful to the kidney and may lead to acute kidney failure.

 

Non-physical causes reported to cause rhabdomyolysis include:

 

Medications:

Statins, especially when prescribed in combinations with fibrates. Cerivastatin (Baycol) was withdrawn in 2001 after numerous reports of rhabdomyolysis. Other statins have a small risk of 0.44 cases per 10,000 patients annually, which increases to 5.98 if a fibrate is added. However, other studies detected no increased risk from statins.

Anti-psychotic medications may cause neuroleptic malignant syndrome, which can cause severe muscle rigidity, with rhabdomyolysis and hyperpyrexia.

Neuromuscular blocking agents, used in anasthesia may cause malignant hyperthermia, also associated with rhabdomyolysis.

Medications that interfere with potassium levels (e.g. diuretics)

 

No peer review to go with the above. It's from Rhabdomyolysis - Wikipedia, the free encyclopedia, for those who wish to check the references.

 

I note that diuretics are used to treat hypertension, a condition often associated with being over-weight and therefore diabetes (more than 85% of hypertension cases occur in those with a body mass index greater than 25, The Lancet). There are plenty of threads on this site exploring the links between weight-loss, cholesterol / lipid levels and blood pressure.

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Hammer

There's a lot of interesting reading here, even if some of it is over my head. Something that I don't see mentioned in these studies is how the side effects are affected by the dosage of the statin. Were the doses high, or were they the bare minimum?

 

I remember reading in the other thread that Merck, the company that makes Zocor ( simvastatin is the generic name), states in the Physician's Desk Reference, that their research indicates that using 10mg of Zocor reduces the LDL levels by 30%. Today, doctors are prescribing 40mg or more, so that makes me wonder if the test results that show all of the side effects are due to an excessive dosage, and I wonder if using the 10mg dose would result in little or no side effects?

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