Statins & Increase Diabetes Risk

Higher-Dose Statins Linked to Moderate Increase in Diabetes Risk
      By Kelly Young
          Edited by Susan Sadoughi, MD , and Jaye Elizabeth Hefner, MD

 Higher doses of statins are associated with greater risk for incident diabetes than lower doses, according to a BMJ study.

Using healthcare databases from Canada, the UK, and the US, researchers identified 137,000 patients who were prescribed statins after hospitalization for a major cardiovascular event. At 2 years, patients prescribed a higher-dose statin (rosuvastatin, 10 mg and up; atorvastatin, 20 mg and up; simvastatin, 40 mg and up) had a 15% higher rate of new diabetes diagnoses than lower-dose statin users. Incidence rates were highest in the first 4 months.

The authors conclude: "Clinicians should consider our study results when choosing between lower potency and higher potency statins in secondary prevention patients, perhaps bearing in mind that head-to-head randomized trials of higher potency versus lower potency statins have not shown a reduction in all-cause mortality or serious adverse events in secondary prevention patients with stable disease."


- See more at: http://www.jwatch.org/fw108892/2014/06/02/higher-dose-statins-linked-moderate-increase-diabetes#sthash.pAKrtJTt.dpuf


and

http://www.bmj.com/content/348/bmj.g3244

Statins Flop in Sepsis and COPD - MedPage

Statins Flop in Sepsis and COPD

By Crystal Phend, Senior Staff Writer, MedPage Today Published: May 18, 2014

 

SAN DIEGO -- Statins don't prevent chronic obstructive pulmonary disease exacerbations or improve outcomes in sepsis-related respiratory failure, a series of trials showed. For patients with acute respiratory distress syndrome (ARDS) from sepsis in the ICU, rosuvastatin (Crestor) didn't cut 60-day in-hospital mortality compared with placebo (28.5% versus 24.9%, P=0.21) or boost ventilator-free days (mean 15.1 in both groups, P=0.96).

Putting patients on the lipid-lowering drug actually contributed to hepatic and renal failure, Jonathon D. Truwit, MD, of the Medical College of Wisconsin in Milwaukee, and colleagues found in the ARDS Clinical Trials Network study.

In the STATCOPE trial, simvastatin (Zocor) didn't prevent COPD exacerbations compared with placebo (1.36 versus 1.39 mean per person-year, P=0.54) or delay them (median 223 versus 231 days to first exacerbation, P=0.34), Gerard Criner, MD, of Temple University in Philadelphia, reported at the meeting.

Both National Heart, Lung, and Blood Institute-sponsored trials were reported at a late-breaking clinical trials session here at the American Thoracic Society meeting and released simultaneously online in the New England Journal of Medicine.
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Read the complete article here. See also NEJM article here.

Statins, Statistics and Statinistics - Sigurdsson

Statins, Statistics and Statinistics

12, May, 2014 by Axel F. Sigurdsson MD

Current medical knowledge is to a large extent based on results from scientific studies. Traditionally, these results are published in peer-reviewed medical journals. Before being accepted, a scientific paper has to go through critical assessment by expert reviewers who will assess the paper’s suitability for publication. The peer review process is intended to guarantee standards of quality and provide credibility. The highest ranked medical journals only accept a small fraction of papers submitted to them for publication.

Clinical medicine relies on the scientific literature. For a clinical cardiologist like myself, this is a key issue. The procedures I decide to perform, and the therapy I recommend is, and should be, based on scientific evidence. For the clinician, evidence based medicine is the holy grail.

But what if  scientific studies are flawed? What if evidence based medicine relies on erroneous data? Then, obviously, clinical medicine is broken.

Unfortunately, the scientific community is not free from dishonesty and greed. Scientific fraud is hard to deal with. Faked data exists and is often difficult to expose. However, we should be able to rely on high quality medical journals when it comes to wrong use of statistics, erroneous calculations and wrong conclusions. These journals should guarantee that papers plagued with such problems are not accepted for publication. But, are they up to the task?

The Statins and the Elderly Saga
One of the most important questions facing clinical cardiology today is when to use statin drugs for individuals who have not been diagnosed cardiovascular disease (CVD). Clinical trials have shown that these drugs lower mortality and reduce the risk of future cardiovascular events among people with CVD. However, in those without established CVD, the magnitude of effect is less clear end it is uncertain when the benefits of therapy outweigh the risks.

Age itself is independently associated with the risk of CVD, and risk factors such as high blood pressure, lipid disorders and diabetes are common among the elderly. However, limited clinical research is available addressing statin treatment among healthy people above 65 years old.
Four months ago I read with interest a paper by Gianlugi Savarese and colleagues, published in the Journal of the American College of Cardiology (JACC) presenting a meta-analysis of the  benefits of statins in elderly subjects without established CVD. The authors concluded that their “meta-analysis provided the first-time evidence that the benefits of statins on major cardiovascular events extended to people above 65 years old”.

In the paper, the authors came to the conclusion that statins significantly reduce the incidence of myocardial infarction (MI) and stroke, but do not significantly prolong survival in the short term.
Their numbers show that 83 patients have to be treated with statins to prevent one case of MI and 142 patients have to be treated with statins to prevent one stroke, for a mean follow-up of 3.5 years. However, they did not present these numbers in their paper. Instead they claimed that 24 patents needed to be treated for 1 year to prevent one MI and that 42 patients needed to be treated for one year to prevent one stroke.

I guess anybody with some statistical knowledge will see that the Number Needed to Treat (NNT) for one year should be a higher number than the NNT for 3.5 years. If one is performing a clinical trial in order to test an effect of a drug, a higher number of patents is needed if the study is planned to run for 1 year than if it is supposed to run for 3.5 years. There will be fewer events in one year than in 3.5 years, therefore the NNT for 1 year is a higher number than the NNT for 3.5 years. If you’re still doubtful, read my earlier blog post on the issue.

My Letter to the Editor of JACC
After discovering the error in the paper by Savarese and colleagues I wrote a letter to the editor of JACC which has been published online before print. I pointed out that the authors appeared to have made an erroneous calculation when reporting the NNT for a period of one year. By using data from their paper I had calculated that the NNT for one year to prevent one MI and one stroke was approximately ten times higher than reported in the paper, given that NNT is constant over time. In other words, the statin effect was exaggerated by a factor of ten.

I also suggested that the most appropriate approach would have been to report the NNT for the mean follow-up of 3.5 years, instead of calculating the NNT for one year.

A correction was published by the authors in JACC on March 25. It’s not very substantial:

“The authors report the number needed to treat (NNT) for the entire mean follow-up of studies was 83 and 142 for myocardial infarction and stroke, respectively. The authors apologize for this error.”

 

Strangely, not a word about the erroneous calculation. The wrong NNT numbers per year are left uncorrected.

Two of the authors of the paper, Gianlugi Savarese and Pasquale Perrone-Filardi, responded to my letter. Their response was published online together with my letter. They agreed that it was more appropriate to report the NNT for the mean follow-up of 3.5 years than presenting the NNT for one year. Furthermore they write:

“As previous authors did (citation) using the same formula adopted in our meta-analysis, our aim was to calculate the NNT per year dividing the overall NNT calculated for the entire trial duration by the length of the follow up. We agree with dr Sigurdsson that this may represent an oversimplification, since this calculation assumes that the effect of the treatment (relative risk reduction) is constant over time and that events occur at a constant rate over time”

Oversimplification is not the right word. Simply put, this is a completely wrong approach. But to my surprise, Savarese and colleagues don’t seem to realize or understand it. In fact dividing, when you should multiply will provide numbers that are very far from the truth.

Repeating an Error Won’t Make it Right 
Of course I was curious to see the paper cited by Savarese and Perrone-Filardi in their response to my letter. It turns out that it’s a paper published in Circulation 2008; “Lipid Management to Reduce Cardiovascular Risk: A New Strategy is Required“, written by H. Roberto Superko and Spencer King III. Dr. King is a world-famous senior cardiologist, a pioneer in cardiac catheterization and coronary angiography.

These two renowned cardiologists address the NNT from a number of statins trials in primary and secondary prevention. Interestingly, they also calculate the NNT per year. The results are published in Table 2. The table shows that the NNT per year is always a higher number than the NNT for the whole study period (which is always longer than one year). For example the NNT to prevent one MI in the famous 4S (SSSS) trial was 11.7 for the whole study period, but the NNT per year of the study was 63.2. The NNT for the WOSCOP trial was 44.2 for the whole study period, but 216.6 per year of the study. In fact, this all looks very reasonable and correct.

But the strange thing is that in the paper’s text, Superko and King use a different approach which is in complete disagreement with the table. They write:

“… such as the Scandinavian Simvastatin Survival Study (SSSS), which achieved an NNT of 11.7 and an NNT per year of 2.2″

And they do this again and again, as if they never saw the table in their own paper. So, Superko and King are dividing the overall NNT by the length of follow-up in order to find the NNT per year. If they continue to do this they will find that the NNT per six months in the 4S-trial was 1.1. This would mean that only one patient had to be treated for six months to prevent one event. Completely absurd.
I wonder, do these renowned scientific authors don’t understand what they’re talking about, or is this just a slight oversight. Whatever it is, it’s serious and unprofessional. How can a respected peer-reviewed paper such as Circulation publish such rubbish? And, five years later Savarese and colleagues decide it’s time to repeat the error. And now it’s accepted by JACC, another highly respected medical journal.

Surprisingly, Savarese and Perrone-Filardi don’t acknowledge their error. Instead, they cite the old paper where the same error was made, and believe that’ll make it right. Furthermore, despite the real NNT being a tenfold higher number than the one they reported (meaning the drug effect is ten times less), they have no intention to reconsider the main conclusion of their study.

I must admit I’m deeply disappointed. The medical community expects much more responsibility from the editorial boards of these medical journals. If the medical literature is full of such errors, our knowledge is worthless? Maybe, in this particular context, lying with numbers, whether it’s done on purpose or not, could be called statinistics instead of statistics. Statinistics could be the new word for badly treated statistics.
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Read the complete article here.

Also see "Statins For Elderly People – A Deceptive Message" by Axel F. Sigurdsson MD

Ezetimibe Prescribing Fails to Keep Up With Evidence - JAMA

Ezetimibe Prescribing Fails to Keep Up With Evidence     

Mike Mitka, MSJ 

             

JAMA. Published online March 19, 2014. doi:10.1001/jama.2014.2896

          

 

Although physicians like to think they practice evidence-based medicine, that appears to not be the case with prescribing the cardiovascular drug ezetimibe. And some critics say that use of surrogate markers to guide practice rather than clinical outcomes such as occurrence of myocardial infarction, stroke, or death has likely played a role.

 

Ezetimibe is an intestinal cholesterol absorption inhibitor found to reduce low-density lipoprotein cholesterol (LDL-C) levels by about 20% when given alone. It also further reduces LDL-C levels when added to statin therapy, which blocks cholesterol synthesis in the liver by inhibiting HMG-CoA reductase.

 

The Food and Drug Administration approved ezetimibe in 2002 for use in the United States primarily because it lowered LDL-C levels, a surrogate marker for prevention of cardiovascular disease. Whether ezetimibe improved clinically meaningful outcomes remained a question.

 

That question was somewhat answered in January 2008, with the announcement that the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial, sponsored and conducted by industry, found that the addition of ezetimibe failed to reduce atherosclerosis progression compared with simvastatin alone, despite lowering LDL-C levels. Atherosclerosis progression was determined by a change in the intima-media thickness of the walls of the carotid and femoral arteries—yet another surrogate end point (Kastelein JJP et al. N Engl J Med. 2008;358[14]:1431-1443).

Place holder to copy figure label and caption

Graphic Jump Location

US and Canadian physicians continue to prescribe ezetimibe even after a study found giving the drug with a statin failed to reduce atherosclerosis progression compared with the statin alone.

 

 

The ENHANCE result prompted some leaders in the cardiology community to question ezetimibe’s place in cardiovascular disease treatment. Harlan Krumholz, MD, professor of medicine and epidemiology and public health at Yale University in New Haven, Connecticut, said the study should change practice. “Although not definitive, [ENHANCE] increases our uncertainty about the clinical value of this novel drug. Without some evidence of improved outcomes associated with its use, ezetimibe should be relegated to a last option for patients who need medication for hypercholesterolemia, and even in these cases, it is reasonable for clinicians and their patients to wait for further information before considering it,” he wrote in NEJM Journal Watch (http://tinyurl.com/pk9xr29).

 

So did the ENHANCE results change practice? In the United States, the answer is “somewhat,” while in Canada, the answer appears to be “no.”

 

In a study published in the American Heart Journal, researchers looked at ezetimibe prescription trends before and after ENHANCE, using data collected from CompuScript in Canada and IMS Health in the United States from January 1, 2002, to December 31, 2009. The researchers found the monthly number of ezetimibe prescriptions per 100 000 population rose from 6 to 1082 in the United States from November 2002 to January 2008 and then declined to 572 per 100 000 population by December 2009, a decrease of 47.1%. In Canada, however, use continuously increased from 2 to 495 per 100 000 from June 2003 (when the drug was approved in Canada) to December 2009 (Lu L et al. Am Heart J. doi:10.1016/j.ahj.2014.01.014 [published online February 27, 2014]).

 

Coauthor Cynthia A. Jackevicius, PharmD, MSc, a professor of pharmacy practice and administration at Western University of Health Sciences in Pomona, California, and an adjunct scientist, Institute for Clinical Evaluative Sciences, in Toronto, said her team was initially surprised by the Canadian results.

 

“Previous findings showed ezetimibe use in Canada experienced a more conservative uptake, so we expected to see a decrease in use in response to the ENHANCE study,” Jackevicius said. “So we looked for different factors, and one is the Canadian lipid guidelines, which specifically said ezetimibe could be added to statins, and that didn’t change after ENHANCE came out.”

A study of ezetimibe use in Saskatchewan, the only Canadian province that lists the drug for open formulary access, even though guidelines say it’s a second-line agent for lowering cholesterol, reflects Jackevicius’s team’s findings. Using data from provincial health administrative databases, the Saskatchewan researchers found that ezetimibe prescriptions were 2.5% of cholesterol-lowering dispensations in 2004 and 8.8% of such dispensations in 2011 (Alsabbagh WM et al. Can J Cardiol. 2014;30[2]:237-243). The authors concluded that allowing unrestricted use of ezetimibe in Saskatchewan may have led to a large number of inappropriate prescriptions, at odds with Canadian clinical guidelines.

 

And although ezetimibe use declined in the United States, its use per 100 000 population is still greater than Canada’s, generating US expenditures of more than $2.2 billion in 2009.

 

Krumholz, one of the coauthors on the study with Jackevicius, remains perplexed as to the continuing popularity of ezetimibe. “The drug continues to defy gravity, and that’s probably a result of really strong marketing and the singular focus on cholesterol numbers,” he said.

 

Krumholz said heart health campaigns urging patients to “know your numbers” and treatment goals based on cholesterol measurements, such as getting asymptomatic individuals’ LDL-C levels below 130 mg/dL, have worked in ezetimibe’s favor at the expense of evidence-based medicine. “Is this the drug that lowers your LDL-C and helps you? We don’t know that,” he said. “The comfort of hitting a target offers little benefit if you don’t know that it is really protecting you.”

 

Although ENHANCE has not derailed ezetimibe prescribing, the newest cholesterol management guidelines just might. The guidelines, issued late last year by the American College of Cardiology and the American Heart Association, abandon the idea of reaching a target level for LDL-C, instead recommending the use of statins to reduce LDL-C levels only for certain types of patients.

Will this change in the guidelines affect ezetimibe prescribing? “It will be interesting to see what the guidelines will do,” Krumholz said.

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Read the complete article here.

Heartwire

Statins Linked to Cataracts in Large, Retrospective Study

Shelley Wood Sep 20, 2013

 

Sponsored

Lowering high cholesterol: Combination therapy vs single statins
Summary of clinical evidence on using combinations of lipid-lowering medications compared to using a statin medication alone.

Get the clinical bottom line

SAN ANTONIO TX — Another large study is linking statin use to the development of cataracts^[1]. The latest, following on a Canadian analysis last year, is a propensity score-matched analysis of over 45 000 subjects in a military healthcare system, published this week in JAMA Ophthalmology .

                   
As Dr Jessica Leuschen (Wilford Hall Ambulatory Surgery Center, San Antonio, TX) and colleagues point out, observational studies of statins have been conflicting, with some suggesting an increased risk of cataracts with statin use while others appear to show a beneficial effect of statins on cataract risk. At the recent European Society of Cardiology (ESC) 2013 Congress , Dr John B Kostis (Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ) presented the results of a random-effects meta-analysis, showing a 20% lower rate of cataracts with statin use compared with no statin use, with a more pronounced benefit seen when statins were started in younger patients.

The meta-analysis published today, however, found the opposite. It matched 6972 statin users with nonusers within the San Antonio Military Multi-Market Area health system using propensity scores based on variables that increased the likelihood of receiving statins and increased the risk of developing cataracts. Statin users had to have been on the drugs for more than 90 days; simvastatin was prescribed in almost three-quarters of the patients.

They found that statin users in the propensity-matched analysis had a 9% increase in cataracts. In secondary analyses that looked at all patients with no comorbidities (based on the Charlson index) at baseline, the risk of developing cataracts was 29% higher in the statin users. Results were consistent regardless of whether patients had been taking statins for two, four, or six years, authors note.
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Read the complete article here.

Another large study is linking statin use to the development of cataracts - Wood

Statins linked to cataracts in large, retrospective study

September 19, 2013 Shelley Wood

            

 

 

 

 

 

 

 

 

 

 

 

San Antonio, TX - Another large study is linking statin use to the development of cataracts [1]. The latest, following on a Canadian analysis last year, is a propensity score-matched analysis of over 45 000 subjects in a military healthcare system, published this week in JAMA Ophthalmology.

 

As Dr Jessica Leuschen (Wilford Hall Ambulatory Surgery Center, San Antonio, TX) and colleagues point out, observational studies of statins have been conflicting, with some suggesting an increased risk of cataracts with statin use while others appear to show a beneficial effect of statins on cataract risk. At the recent European Society of Cardiology (ESC) 2013 Congress, Dr John B Kostis (Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ) presented the results of a random-effects meta-analysis, showing a 20% lower rate of cataracts with statin use compared with no statin use, with a more pronounced benefit seen when statins were started in younger patients. 

 

The meta-analysis published today, however, found the opposite. It matched 6972 statin users with nonusers within the San Antonio Military Multi-Market Area health system using propensity scores based on variables that increased the likelihood of receiving statins and increased the risk of developing cataracts. Statin users had to have been on the drugs for more than 90 days; simvastatin was prescribed in almost three-quarters of the patients.

 

They found that statin users in the propensity-matched analysis had a 9% increase in cataracts. In secondary analyses that looked at all patients with no comorbidities (based on the Charlson index) at baseline, the risk of developing cataracts was 29% higher in the statin users. Results were consistent regardless of whether patients had been taking statins for two, four, or six years, authors note.

 

The study is the first to use propensity matching to try to eliminate baseline confounding—making it a key contribution to the relatively recent research into this potential interaction. To heartwire, senior author Dr Ishak Mansi (VA North Texas Health Care System, Dallas) noted that there are a number of ways in which statins could be a marker for important confounders, including accessible healthcare and health insurance, as well as underlying risk factors such as smoking, diabetes, and older age—all of which are also risk factors for cataract.

 

That kind of confounding may have been a factor in the Kostis et al meta-analysis at ESC, Mansi commented, when asked about the divergent findings, adding that since the paper is not yet published, he hasn't had a chance to review its methodology.

 

"Without knowing the specifics of the paper . . . I can generally say the following: During the mid-1990s and early 2000s, there were many papers that associated statin use with improved outcomes of many diseases such as cataract, fracture, infection, dementia, etc; however, recently, it was realized that statin use was associated with 'healthy-user bias.' That is to say, individuals who are health-conscious are more likely to take statins, and better outcomes may be secondary for their health consciousness and not due to the statin itself. . . . Therefore, if this meta-analysis included large-volume studies that date back to this period of time, their results may be affected by these biases of these studies."

 

Cardiologists have had plenty of experience with seemingly contradictory studies, he added. "Historically, we have been through these controversies on several topics, such as the use of hormonal-replacement therapy, treatment of chronic systolic heart failures with antiarrhythmic drugs, etc. We will have to study and search for our best capabilities until we reach an answer."

 

"Statins are very effective medications; therefore, side effects are expected. Healthcare providers should make sure that there is justifiable indication to prescribe statins according to guidelines and that the potential benefits outweigh the potential risks of side effects for individual patients. These medications should not be prescribed lightly."

 

For the public, however, the message is slightly different. "For some patients, these medications have been a main tool in treatment of heart disease and should not be stopped because of a small higher risk of association with other diseases," Mansi said. All effective medications can be expected to have side effects, he continued. "It is much better to do your best to lower your own risk of cardiovascular disease (if feasible) by stopping smoking and keeping physically active than to take a pill to lower your risk of heart disease."

 

Source

1. Leuschen J, Mortensen EM, Frel CR, et al. JAMA Ophthalmol 2013; DOI:10.1001/.jamainternmed.2013.4575. Available at: http://archopht.jamanetwork.com/journal.aspx.

Related links

• Statins linked with development of cataracts
  [Lipid/Metabolic > Lipid/Metabolic; Aug 13, 2012]
• Genetic marker may identify risk for statin-induced myopathy
  [Clinical Conditions > Lipid/Metabolic; Sep 06, 2013]
• Treat risk and not LDL-cholesterol targets, new perspective argues
  [Lipid/Metabolic > Lipid/Metabolic; Jan 19, 2012]

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Read the complete article here.http://www.theheart.org/article/1584825.do

 

Antibiotics and Statins: A Deadly Combo? - Laino

Antibiotics and Statins: A Deadly Combo?

By Charlene Laino, Senior Writer, Gupta Guide

Published: June 19, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

For best viewing, click the bottom right corner for full screen.

Action Points

• Prescribing clarithromycin or erythromycin to older patients taking the most commonly prescribed statins raised the risk for statin toxicity.
• Point out that to decrease the risk of statin toxicity for a patient who requires a mycin antibiotic, the study authors suggested that azithromycin is the best option.

Prescribing clarithromycin or erythromycin to older patients taking the most commonly prescribed statins, which are metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4), raised the risk for statin toxicity, according to a population-based retrospective cohort study.

Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome CYP3A4, and that inhibition increases blood concentrations of statins that are metabolized by CYP3A4 to potentially dangerous levels, Amit M. Patel, MD, of the London Health Sciences Center in Ontario, and colleagues reported online in the Annals of Internal Medicine.

Compared with azithromycin, co-prescription of atorvastatin, simvastatin, or lovastatin with clarithromycin or erythromycin was associated with a 0.02% increase in the absolute risk of hospitalization with rhabdomyolysis within 30 days (95% CI 0.01%-0.03%). That translates to a relative risk increase of 2.17 (95% CI, 1.04-4.53).
Risks were also increased for:

• Acute kidney injury -- absolute risk increase, 1.26% (95% CI 0.58%-1.95%); RR 1.78 (95% CI 1.49-2.14)
• All-cause mortality -- absolute risk increase, 0.25% (95% CI 0.17%-0.33%); RR 1.56 (95% CI 1.36-1.80)

"Statins are the No. 1 class of drugs prescribed in North America," co-author Amit Garg, MD, PhD, also from the London Health Sciences Center, said in a statement.

Coprescription of a statin with a macrolide antibiotic is very common. Until now, the clinical and population-based consequences of this potential drug-drug interaction were unknown, he said.
While the absolute risk increase is relatively small, "given the frequency at which statins are prescribed and the high rate of coprescription seen in our study and in other jurisdictions, this preventable drug-drug interaction remains clinically important. The results suggest many deaths and hospitalizations due to acute kidney injury in Ontario may have been attributable to this interaction, the researchers wrote.

For the study, the researchers examined the frequency of statin toxicity in continuous statin users older than 65 years who were prescribed clarithromycin (n=72,591) or erythromycin (n=3,267), compared with azithromycin (n=68,478) in Ontario from 2003 to 2010.

The primary outcome was rhabdomyolysis within 30 days of the antibiotic prescription.
The most commonly prescribed statin was atorvastatin (73%), followed by simvastatin (24%) and lovastatin (3%).

American Heart Association spokesperson Robert Eckel, MD, of the University of Colorado at Denver, said that although the potential for drug-drug interactions between certain antibiotics and statins was known, this study really underscores the potential for dangerous, even fatal complications.
"And while the study was only done in elderly patients, this "provides a signal" these complications could develop in younger people as well," he told "The Gupta Guide."

There's another option too, said John Higgins, MD, of the University of Texas Health Science Center at Houston. "If you have a patient on a statin and you need a mycin antibiotic, the study suggests you choose azithromycin.

"But there is also a statin that is not metabolized by the CYP3A4 system -- pravastatin. So you really have two choices here. Switch the antibiotic or switch the statin," he said.

The study has several major strengths, including its large size, Eckel said
But there are limitations, too, Higgins said. "For example they only studied people over 65, with a median age of 74, who may have a lot of comorbidities. So these patients may be more prone to some of these problems anyway," he said.

Additionally, it is an observational study and therefore subject to all the biases of such an analyses -- that is, they show associations, but cannot prove casual relationships, he said.
Finally, "coders record the health problems and we know that coders often don't note complications in all patients," Higgins said. "So, if anything, the risks may have been higher than those found in the study," he said.

Also, the researchers themselves noted that despite the large sample size, they could "not meaningfully examine interactions with each CYP3A4-metabolized statin individually. However, given the known effect on CYP3A4 statin pharmacokinetics, it remains prudent to generalize the coprescription warning to atorvastatin, simvastatin, or lovastatin with clarithromycin or erythromycin," they wrote.

Said Patel, "The results provide important safety information regarding these commonly prescribed medications. When prescribing clarithromycin or erythromycin to patients on these statins, preventive measures should be considered, such as cessation of the statin for the duration of the antibiotic therapy, increased monitoring for adverse events, or use of a different antibiotic that does not interact with these statins."

The authors also suggested that clinicians take advantage of free online drug interaction programs and/or software aimed at improving the overall safety of polypharmacy in older adults.
And there's always the obvious solution: Better multidisciplinary collaboration between departments, Eckel added.

Do you double-check what statins your patients are on before prescribing an antibiotic? Add Your Knowledge below. -- Sanjay Gupta, MD.

The investigators received grant support from the Academic Medical Organization of Southwestern Ontario to conduct this research. This project was conducted at the Institute for Clinical Evaluative Sciences site at Western University. The Institute for Clinical Evaluative Sciences is funded by an annual grant from the Ontario Ministry of Health and Long-term Care. The Institute for Clinical Evaluative Sciences site at Western University is funded by an operating grant from the Academic Medical Organization of Southwestern Ontario. Dr. Garg was supported by a Canadian Institutes of Health Research Clinician Scientific Award.
Eckel and Higgins have no financial conclicts of interest to disclose.

Primary source: Annals of Internal Medicine
Source reference:Patel AM, et al "Statin toxicity from macrolide antibiotic coprescription" Ann Intern Med 2013; DOI: 10.7326/0003-4819-158-12-201306180-00004.
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Read the complete article here.

Licence for another unproven cholesterol drug - Briffa

The FDA grants licence for another unproven cholesterol drug

By Dr John Briffa on 8 May 2013

 

Ezetimibe is a drug that lowers cholesterol levels by blocking its absorption from the gut. The drug is available under the brand name Zetia. Doctors can also prescribe ezetimibe in combination with the statin drug simvastatin. This combination medication is sold under the name Vytorin. Both Zetia and Vytorin have racked up billions of dollars in sales. What a shame, then, that neither of them has been found to have any benefit at all in terms of reducing the risk of heart disease, heart attacks, strokes or risk of death.

Zetia and Vytorin are licenced on the basis of their impact on cholesterol levels. The thinking is that LDL-cholesterol must be bad, so anything that reduces it must be good. However, we know from experience that many things that ‘improve’ cholesterol do not bring broad benefits to health. And besides, it’s simply not good science or medicine to assume that a drug has benefits for health based on its impact on what is known as a ‘surrogate marker’ such as cholesterol. I mean, if arsenic reduced cholesterol it still would not make sense for us to swig back arsenic each day, would it?

This seems like perhaps an extreme analogy, but it should be borne in mind, I think, the Vytorin use has in some studies been associated with an increase (not statistically significant) in the thickening of the arteries compared to simvastatin alone. Also, there was some early evidence the Vytorin increased the risk of death from cancer, though some more recent evidence is said to have allayed fears here.

While some doctors continue to prescribe Zetia and Vytorin it’s difficult (for me) to justify this. There is some evidence that since 2008 (when we saw the first of a few negative studies on Zetia/Vytorin emerge) sales of these drugs have fallen considerably, though profit remains considerable. Make no mistake, though, the fact that Zeta/Vytorin is still on the market and was licensed in the first place is seen by some doctors and researchers as testament to the ability of drug companies to bamboozle regulatory authorities such as the Food and Drugs Administration (FDA) in the US. Either that, or the FDA is perhaps putting the needs of drug companies above those of patients.

Against this background, it is interesting to note that Merck (manufacturer of Vytorin) has been for some years attempting to get another similar drug combination passed by the FDA. The drug combines ezetimibe with the statin atorvastatin and has the brand name Liptruzet. As with Vytorin, there exists no evidence that Liptruzet benefits so-called ‘clinical’ outcomes such as incidence of heart disease and stroke.

Now, given all the controversy around Vytorin and the lack of evidence for the benefit of this product, you might imagine the FDA would be keen not to repeat its mistake by granting Liptruzet a licence. Astonishingly, though, the FDA did just this last week.

Now, normally, when a new drug hits the market the press reports parrot the drug company rhetoric about, say, the benefits of the drug and the lives it could save. What is interesting about the press reports on the licensing of Liptruzet is how many of them report scepticism regarding the wisdom of this decision expressed by doctors and researchers. See here for an example.

The piece quotes Steven Nissen, chairman of cardiology at the Cleveland Clinic in the US. According to Dr Nissen, the FDA’s decision to approve the Liptruzet “just doesn’t make any sense.” He is quoted as saying:

I find it astonishing that after all the controversy about ezetimibe the FDA would approve another combination product with a drug that has been on the market for a decade and has not been shown to improve cardiovascular outcomes. It seems like the agency is just tone deaf to the concerns raised by many members of the community about approving drugs with surrogate endpoints like cholesterol without evidence of a benefit for the disease we are truly trying to treat – cardiovascular disease.

And what does Merck have to say for itself? According to spokeswoman Pamela Eisele, Merck is “confident in ezetimibe and in the established relationship between lowering LDL cholesterol and reducing cardiovascular events.”

Merck can be confident all it likes in ezetimibe and its products Zetia, Vytorin and Liptruzet, but the fact is, none of these have been shown to lower ‘cardiovascular events’. My personal opinion is that either Merck is full of idiots or is taking us for idiots. The good news is that the sort of rhetoric spouted by Merck is immediately being recognised by some as having a distinct whiff of b.s. about it.
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Reaqd complete article here.

Fears of cancer link to statin - AB Rossebo,

Scientists raise fears of cancer link to statin used by thousands

 

This post includes a synopsis of a study published in the New England Journal of Medicine September 25, 2008; 359(13): 1343-56 and a recipe for roccoli, bacon and nut salad.

Study title and authors:

Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.
AB Rossebo, TR Pedersen, K Boman, P Brudi, JB Chambers, K Egstrup, E Gerdts, C Gohlke-Barwolf, I Holme, YA Kesaniemi, W Malbecq, CA Nienaber, S Ray, T Skjaerpe, K Wachtell, R Willenheimer, and SEAS Investigators Division of Cardiology, Aker University Hospital, Trondheimsveien 235, N-0514 Oslo, Norway.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/18765433

This trial observed the effects of the drug Inegy (a combination of simvastatin and ezetimibe).The trial was a randomizsd, double-blind trial involving 1,873 patients with mild-to-moderate, asymptomatic aortic stenosis (obstruction of blood flow across the aortic valve). The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily and were followed for 52 months.

The study found:

(a) Those taking the simvastatin/ezetimibe combination had a 4% increased risk of death compared to those taking placebo.

(b) Those taking the simvastatin/ezetimibe combination had a 21% increased risk of death from heart failure compared to those taking placebo.

(c) Those taking the simvastatin/ezetimibe combination had a 67% increased risk of death from cancer compared to those taking placebo.

(d) Those taking the simvastatin/ezetimibe combination had a 195% increased risk of death from violence or accidents compared to those taking placebo.

Professor Heinz Drexel, of the University of Innsbruck in Austria and spokesman for the European Society of Cardiology, said: "I am not sure that the efficacy is proven and I am not sure that the safety is proven. I wouldn't take the drug myself".

In Britain, about 300,000 NHS prescriptions have been dispensed for Inegy in the last two years.
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High potency cholesterol drugs linked to risk of kidney injury- Branswell

Use of high potency cholesterol drugs linked to risk of kidney injury: Study

By Helen Branswell, The Canadian Press

 

TORONTO - The use of high potency versions of cholesterol lowering drugs called statins may increase a person's risk of developing kidney failure, a new study suggests.

 

The research found that when compared to low dose statin regimens, high potency versions of the pills were linked to slightly elevated rates of acute kidney injury.

The researchers, who are from institutions across Canada, estimate that for every 1,700 people who used high dose statins for 120 days, you would expect to see one more person hospitalized with kidney failure.

While that number may seem small, a drug safety expert who wasn't involved in the work noted that use of these drugs is common.

"Tens of millions of North Americans take these drugs, and so even side-effects that are relatively uncommon are important," said Dr. David Juurlink, a specialist in internal medicine and clinical pharmacology at Toronto's Sunnybrook Health Sciences Centre.

"The findings strongly suggest that high-dose statins can cause acute kidney injury.... Most clinicians don't generally perceive statins to be a potential cause of kidney injury. Hopefully this study will change that perception, and make us all a bit more careful of how we use these drugs."

The research was produced by the Canadian Network for Observational Drug Effect Studies, which is funded by Health Canada. The study was published in the journal BMJ.

Lead author Colin Dormuth said previous studies have shown hints that high potency statins may increase the risk of kidney failure, but the studies were not large enough to provide more than a signal of a potential problem. If the increased risk only shows up at a rate of one additional case per 1,700 people treated, a study would need to be very large to ensure that effect was real and not merely a chance observation.

So Dormuth and his colleagues pooled data on more than two million people who took statins, comparing those who took high potency formulations to those taking lower doses of the drugs. People included were aged 40 and older and started taking statins between the beginning of 1997 and April 30, 2008.

The data were drawn from databases from seven Canadian provinces as well as from Britain and the United States. About a third of the 2,067,639 people in the study were using high potency statins.
"We thought given that so many people use these medications that it was really important to try to determine if there was an association between statin potency and risk of acute kidney injury," said Dormuth, who is an epidemiologist with the University of British Columbia's Therapeutics Initiative. The program uses an evidence-based approach to drug therapy to try to balance the information sources funded by the pharmaceutical industry.

High potency statins were defined as 10 milligrams or more of rosuvastatin (sold under the brand name Crestor), 20 mg or more of atorvastatin (sold under the brand name Lipitor) and 40 mg or more of simvastatin (sold under the brand name Zocor). All other statins were considered to be low potency.

The kidney problems, when they occurred, seemed to materialize early in the treatment, generally within 120 days. But the risk of kidney injury associated with high potency statins remained elevated for at least two years, the study found.

An editorial on the issue that ran with the study said that despite the broad use of statin drugs, the science of finding the Goldilocks dosage — maximizing benefit while minimizing risk — was still evolving.

Still, Robert Fassett and Jeff Coombes, professors from the University of Queensland in Brisbane, Australia, said doctors should make note of the Canadian findings.

"The results of the current study indicate that clinicians should use low potency statins whenever possible to provide cardiovascular benefits without the increased risk of acute kidney injury," they wrote.

Dormuth said he and his colleagues are not suggesting there is no place for high potency statins. Rather, he suggested, people considering taking these drugs should talk with their doctors about their risk of heart disease and how it stacks up against the risk of taking these drugs.

"We're seeing patients younger and healthier getting the drugs," he said.

"This is where the 1,700 number needs to be put in context with other known harms, such as rhabdomyolysis (and) diabetes, and that needs to be weighed against the expected benefit. And the expected benefit of taking a statin is very small in younger, healthier people — particularly women."

Rhabdomyolysis is a potential side-effect of statin use. It is a condition where muscle tissue breaks down and is released into the blood stream, which can lead to kidney damage.
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Read the complete article here.

Myositis from Statin and PPI Drugs - Dach

A Neurosurgeon with a Painful Arm, Myositis from Statin and PPI Drugs by Jeffrey Dach MD

Sam, a 67 year old retired neurosurgeon came to see me because of pain and weakness in his right arm over the past 6 months. The pain and weakness is chronic and so severe, that he has given up Golf, his favorite pastime. His medical history is unremarkable except for his medications which includes a statin drug to lower cholesterol, simvastatin, which he has been taking for three years, and Prilosec a proton pump inhibitor (PPI) acid blocking drug for the past year for symptoms of heart burn.
Upon examination, there is diffuse tenderness of the muscles of the right shoulder and arm, as well as generalized muscle wasting.

Lab studies revealed extensive vitamin and mineral deficiencies suggesting malabsorption, B12 was low at 337 . There was a very low cholesterol level of 146.

My diagnosis was drug induced myositis from the combination of statin drug and proton pump inhibitor acid blocking drug. I advised the retired Neurosurgeon to stop these drugs and to take vitamin and mineral supplements to allow the muscles to heal.

Sam’s cardiologist and gasteroenterologist disagreed with my assessment and objected to the idea of stopping the drugs. They told Sam that these were “lifesaving drugs”. and were unlikely to be related to the muscle problems, and to continue them. In addition, Sam didn’t need any vitamins, as he was getting all his vitamins from his diet. Sam relayed this information to me on the phone. He thanked me for seeing him, but he would follow the advice of his other doctors, the cardiologist and the gasteroenterologist who he had known for years and trusted them.

Six months later, Sam’s wife called me to ask if there was anything I could do for Sam. He was still taking the statin anti-cholesterol drugs and the acid blocking drug ( PPI), and Sam’s conditionn had deteriorated to the point he was now in a wheel chair in a nursing home with early dementia.

Myopathy and Myositis are well known adverse effects of statin drugs which lower cholesterol. They also lower CoQ-10 levels and serve as mitochondrial toxins causing myopthy and dementia. The PPI drugs are also known to cause myopathy, thought to be caused by protein, mineral and vitmain malabsorption from lack of stomach acid.(1-9)



Links and References
Myopathy caused by proton pump inhibitors and statins
1) http://www.ncbi.nlm.nih.gov/pubmed/16758264
Eur J Clin Pharmacol. 2006 Jun;62(6):473-9. Epub 2006 Apr 22.
Myopathy including polymyositis: a likely class adverse effect of proton pump inhibitors? Clark DW, Strandell J.Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand.
Polymyositis occurring in patients treated with omeprazole has been signalled as a possible adverse drug reaction (ADR) by the New Zealand Intensive Medicines Monitoring Programme (IMMP) and the WHO Collaborating Centre for International Drug Monitoring: the Uppsala Monitoring Centre (UMC). Polymyositis and other myopathies have also been reported in post-marketing data and in the medical literature in association with proton pump inhibitor (PPI) use. We wished to follow-up these signals and investigate the evidence of causality for the association of polymyositis and other myopathy with PPI use.
METHODS: Spontaneously reported ADRs from national monitoring centres are sent to the WHO ADR database (VigiBase). VigiBase was searched for case reports of the PPIs, omeprazole, pantoprazole, lansoprazole, esomeprazole and rabeprazole, with terms indicative of myopathy, and further information was elicited from the national centres to help establish causality. Literature sources were reviewed for the occurrence of the above terms in combination with PPIs.
RESULTS: In total, there were 292 reports of various myopathies with PPIs, excluding 868 cases of ‘myalgia’. In this analysis, 69 patients recovered when the drug was withdrawn and, in 15 patients, the reaction re-occurred when the drug was reinstated. In one-third of the 292 cases, the PPI was the single administered drug, and the PPI was the single suspected drug by the reporter in 57% of reports where concomitant medication was used. In this analysis, three index cases are documented. One involves the same patient taking three different PPIs (lansoprazole, esomeprazole and rabeprazole) at different time periods, with myalgia and muscle weakness occurring with all three drugs. In the two other index cases, myopathies with esomeprazole and omeprazole were reported with positive rechallenge, and causality was assessed as ‘possible’ and ‘certain’ by the reporting centres. In 27 cases myositis or polymyositis was reported. Other myopathies were reported, including 35 cases with rhabdomyolysis. In 9 of these cases, the PPI was withdrawn and the reaction abated. The PPI was reinstated in one patient, but the reaction did not re-occur. Time to onset was given in 17 of the rhabdomyolysis cases, rhabdomyolysis occurred with the first week in 9 cases, and in 3 cases the reaction occurred between 14 days to 3 months of treatment. In 12 of these patients, an HMG-CoA reductase inhibitor (statin) was taken concomitantly.
CONCLUSION: Case reports from the WHO ADR database, including index cases involving four out of five PPIs, along with evidence of a possible mechanism, provide compelling evidence that there is a causal association between members of the PPI drug class and myopathy including polymyositis. Evidence was also obtained to support the view that PPI use may be associated with occurrence of other myopathies, including the serious reaction rhabdomyolysis.
statin induced myopathy
2) http://www.ncbi.nlm.nih.gov/pubmed/12672737
JAMA. 2003 Apr 2;289(13):1681-90.
Statin-associated myopathy. Thompson PD, Clarkson P, Karas RH.Preventive Cardiology and Cardiovascular Research, Division of Cardiology, Hartford Hospital, Hartford, Conn 06102, USA.
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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3) http://www.ncbi.nlm.nih.gov/pubmed/22560377
Eur J Intern Med. 2012 Jun;23(4):317-24.
Statin induced myotoxicity. Sathasivam S. The Walton Centre NHS Foundation Trust, Lower Lane, Liverpool L9 7LJ, United Kingdom.
Statins are an effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, myotoxicity induced by statins is a common adverse event and a major barrier to maximising cardiovascular risk reduction. The clinical spectrum of statin induced myotoxicity includes asymptomatic rise in creatine kinase concentration, myalgia, myositis and rhabdomyolysis. In certain cases, the cessation of statin therapy does not result in the resolution of muscular symptoms or the normalization of creatine kinase, raising the possibility of necrotizing autoimmune myopathy. There is increasing understanding and recognition of the pathophysiology and risk factors of statin induced myotoxicity. Careful history and physical examination in conjunction with selected investigations such as creatine kinase measurement, electromyography and muscle biopsy in appropriate clinical scenario help diagnose the condition. The management of statin induced myotoxicity involves statin cessation, the use of alternative lipid lowering agents or treatment regimes, and in the case of necrotizing autoimmune myopathy, immunosuppression.
4) http://www.ncbi.nlm.nih.gov/pubmed/22154355
Atherosclerosis. 2012 May;222(1):15-21.
Statins as a possible cause of inflammatory and necrotizing myopathies. Padala S, Thompson PD.
Department of Internal Medicine, University of Connecticut, Farmington, CT 06030, USA.
Hydroxy-methyl-glutaryl Co-A reductase (HMGCR) inhibitors or statins are a well recognized cause of a variety of skeletal myopathic effects which generally resolve on stopping the medication. Recent reports, however, suggest that statins are associated with a unique autoimmune myopathy wherein symptoms persist or even progress after statin discontinuation and require immunosuppressive therapy. We performed a systematic review to examine the association of statins with inflammatory (dermatomyositis/polymyositis) and necrotizing myopathies.
METHODS: We searched PubMed, Ovid and Scopus for English language articles addressing statin associated inflammatory and necrotizing myopathies. Given the paucity of cases, we extended the search to include articles in all languages.
RESULTS: The search yielded 14 articles reporting a possible association of statins with inflammatory myopathies describing 10 cases of polymyositis and 14 cases of dermatomyositis, and 4 articles reporting a possible association of statins with necrotizing myopathies describing 63 cases. One study identified a unique antibody directed against HMGCR in patients with necrotizing myopathy. Systemic immunosuppressive therapy was required in majority of these cases for resolution of symptoms.
CONCLUSION: Statins have recently been associated with a variety of inflammatory myopathies including polymyositis, dermatomyositis, and a necrotizing myopathy. The association of statins with necrotizing myopathy is strengthened by the discovery that the serum of some of these patients contains an anti-HMGCR antibody. This suggests that statins can cause or unmask an immune mediated myopathy.
5) http://www.if-pan.krakow.pl/pjp/pdf/2011/4_859.pdf
Pharmacol Rep. 2011;63(4):859-66.
Statin-induced myopathies. Tomaszewski M, Stępień KM, Tomaszewska J, Czuczwar SJ.
Source Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, PL 20-954 Lublin, Poland.
Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medications. The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis. Clinical trials commonly define statin toxicity as myalgia or muscle weakness with creatine kinase (CK) levels greater than 10 times the normal upper limit. Rhabdomyolysis is the most severe adverse effect of statins, which may result in acute renal failure, disseminated intravascular coagulation and death. The exact pathophysiology of statin-induced myopathy is not fully known. Multiple pathophysiological mechanisms may contribute to statin myotoxicity. This review focuses on a number of them. The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk. Currently, the only effective treatment of statin-induced myopathy is the discontinuation of statin use in patients affected by muscle aches, pains and elevated CK levels.
Free full text
6) http://www.ncbi.nlm.nih.gov/pubmed/20688875
Phys Ther. 2010 Oct;90(10):1530-42.
Effects of statins on skeletal muscle: a perspective for physical therapists.Di Stasi SL, MacLeod TD, Winters JD, Binder-Macleod SA.SourceUniversity of Delaware, Newark, Delaware, USA.
Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy.
7) http://www.ccjm.org/content/78/6/393.long
Statin myopathy: A common dilemma not reflected in clinical trials Cleveland Clinic Journal of Medicine June 2011 vol. 78 6 393-403 GENARO FERNANDEZ, MD ERICA S. SPATZ, MD CHARLES JABLECKI, MD Department of Neurosciences, University of California San Diego, La Jolla PAUL S. PHILLIPS, MD⇓ Director, Interventional Cardiology, Department of Cardiology, Scripps Mercy Hospital, San Diego, CA
myopathy and muscle pain while on the combined treatment of atorvastatin plus ezetimibe.
8) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538990/
Can J Cardiol. 2006 February; 22(2): 141–144.
Ezetimibe-associated myopathy in monotherapy and in combination with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor Chantale Simard, B Pharm, PhD, and Paul Poirier, MD PhD FRCPC FACC
Centre de recherche, Hôpital Laval; Faculté de Pharmacie, Université Laval, Sainte-Foy, Québec
Correspondence: Dr Chantale Simard, Centre de recherche, Hôpital Laval, 2725 chemin Sainte-Foy, Sainte-Foy, Québec
9) http://www.ncbi.nlm.nih.gov/pubmed/17768174Ann Rheum Dis. 2008 May;67(5):614-9.
Increased exposure to statins in patients developing chronic muscle diseases: a 2-year retrospective study.Sailler L, Pereira C, Bagheri A, Uro-Coste E, Roussel B, Adoue D, Fournie B, Laroche M, Zabraniecki L, Cintas P, Arlet P, Lapeyre-Mestre M, Montastruc JL.Unit of Pharmacoepidemiology, EA 3696, Clinical Pharmacology Department, Paul Sabatier University, 37 Allées Jules Guesdes, 31000 Toulouse, France.

Case reports have suggested that lipid-lowering drugs (LLDs), especially statins, could induce or reveal chronic muscle diseases. We conducted a study to evaluate the association between chronic muscle diseases and prior exposure to LLDs.METHOD:This was a retrospective study of chronic primary muscle disease cases newly diagnosed at the Toulouse University Hospitals between January 2003 and December 2004 among patients living in the Midi-Pyrénées area, France. All patients remained symptomatic for more than 1 year after drug withdrawal, or required drugs for inflammatory myopathy. Data on the patient’s exposure to LLDs and to other drugs were compared with that of matched controls (5/1) selected through the Midi-Pyrénées Health Insurance System database.RESULTS:A total of 37 patients were included in the study. Of those, 21 (56.8%) suffered from dermatomyositis (DM) or polymyositis (PM), 12 (32.4%) from genetic myopathy, and 4 (10.8%) from an unclassified disease. The prevalence of exposure to statins was 40.5% in patients and 20% in controls (odds ratio (OR) 2.73, 95% confidence interval (CI) 1.21-6.14; p<0 .01="" strong="">There was a significant positive interaction between statins and proton pump inhibitors exposure (weighted OR 3.3, 95% CI 1.37-7.54; p = 0.02).

Statin exposure rate was 47.6% among patients with DM/PM (OR 3.86, 95% CI 1.30-11.57; p<0 .01="" and="" between="" border="0" controls="" difference="" exposure="" fibrates.conclusion="" for="" img="" no="" patients="" src="http://jeffreydach.com/emoticons/tongue.png" there="" to="" was="">atients who developed chronic muscle diseases after the age of 50, including DM/PM, had a higher than expected frequency of prior exposure to statins. Further studies are needed to confirm this association and the role of proton pump inhibitors.

warmest regards,

Jeffrey Dach MD

Offices of Willow Grove

7450 Griffin Road, Suite 190

Davie, Fl 33314

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The Dark Side of Statins - Colpo

The Dark Side of Statins: Stroke, Muscle Breakdown, Kidney Failure & More

from AnthonyColpo by Anthony Colpo

If you’ve read The Great Cholesterol Con, the name Brian Barker should ring a bell. Brian was featured in Chapter 9 of the book, where I described the life-changing events that took place after his doctor prescribed him a statin drug. Brian remains very ill to this day, and his experiences both sadden and infuriate me. I met Brian and his lovely wife Heather in Sydney in 2005, and it was dispiriting to see such truly nice folks have to suffer what they’ve been through, and it’s infuriating to realize they’re victims of a patently stupid medical mindset that often views toxic statin drugs as wonder pills that should be prescribed freely to everyone over fifty. Ironically, Brian had no personal history of heart disease whatsoever, but his doctor at the time – faithful believer of drug company and medical authority propaganda that he was – figured he’d throw Brian on simvastatin anyhow, “just as an extra precaution”. This flippantly prescribed and utterly unnecessary “extra precaution” transformed Brian from a healthy, active man into a chronically and seriously ill patient who now needs others to help him with the most basic of daily tasks.

In this article, Heather Barker describes their ordeal in full, from that fateful day in May 2002 when Brian was first prescribed a statin drug, to the present, where he continues to struggle not only with ill health but a callous New Zealand health bureaucracy that seems hellbent on denying Brian the financial compensation he is legally entitled to.

A statin is a lipid-lowering agent and although the mechanism is not fully understood or agreed upon by the medical professionals – statins do appear to lower cholesterol. However is the lowering of cholesterol beneficial in reducing heart mortality and what are some of the consequences of lowering cholesterol? This is my personal experience and I do not wish to contradict or undermine those people who tirelessly work towards lowering cardiovascular disease.

My husband Brian and I live in Auckland, New Zealand. Brian was an active person who enjoyed walking, swimming, writing and watching sport. He had solid computer skills in his job with a major airline and was responsible for paying about 700 staff. Brian was a good communicator and was extremely thorough and analytical in his work. He was able to do complex equations in his head and prided himself on accuracy. Honesty and confidentially were key to this job. He also contributed short stories to books held in the National Library and enjoyed looking forward to planned holidays.

That was until a weekend in June 2002 when our lives changed forever. On May 1st 2002 Brian started taking a statin prescribed by a cardiologist based on Brian’s family history and not his health. The cardiologist agreed he was physically fit and did not otherwise meet the criteria for a statin. No blood tests were taken.

Several weeks later Brian became seriously ill with a life threatening event we now know is called rhabdomyolysis which means his muscle tissue melted. This caused acute renal failure. Our GP did not recognize the symptoms which included severe pain in the right flank, frequent vomiting, nausea, no urine output, confusion and weakness.

The GP did not feel it was necessary to do blood tests until pressured by me to do so. When the test results showed Brian had renal failure the doctor’s response was to get Brian to drink a further 4 litres of water. This exacerbated the already dangerous situation. It was 5 days after the initial onset of these symptoms before Brian was hospitalized.

Caused by Simvastatin

Once hospitalised at North Shore Hospital the doctors examined Brian and confirmed the renal failure due to the statin. Neither of us understood most of what was said but were grateful for their help. Brian was transferred to the renal unit at Auckland Hospital and started dialysis. This was now 7 days after the onset of symptoms.

During the course of his treatment both in the hospital and as an outpatient, Brian and I mentioned his weakness, pain, nausea, tingling sensations in many of his muscles, fatigue and frequency in urinating once his kidneys started working again. The list also included urinary incontinence, impotence, confusion, tiredness, widespread discomfort, nightmares, anxiety, thumping headaches and an inability to seize and understand facts.

While he was on dialysis Brian had what we were told 3 years later was a stroke. Neurologists have told us this was due to the extreme stress his body was under in addition to the toxicity from the statin.

Reporting the Problem

Mandatory reporting of adverse reactions is not required in NZ, so I gave the information to the Centre for Adverse Reactions in Dunedin and it was also recorded at the WHO database by Merck Sharp and Dome.

Brian remained on dialysis for some time and eventually his kidney function returned but he remained very ill and was unable to do much without assistance.

Getting Compensated

In New Zealand we have a compulsory accident cover. It is called the Accident Compensation Corporation. ACC is the sole and compulsory provider of accident insurance for all work and non-work injuries. The ACC Scheme is administered on a no-fault basis, so that anyone, regardless of the way in which they incurred an injury, is eligible for coverage under the Scheme. Due to the Scheme’s no-fault basis, people who have suffered personal injury do not have the right to sue an at-fault party, except for exemplary damages.

ACC  accepted our claim that Brian had a medical misadventure and he was assured by his case manager at ACC that any future treatment relating to his injury – for the duration of his life would be covered by ACC. This was in 2002.

ACC provided support with speech language therapists, physiotherapists, psychologists and ongoing treatment from muscular skeletal specialists.

When Brian did not make a full recovery he was retired from his employment and I left my full time job to assisted Brian with day to day tasks like showering and getting dressed. Making decisions were now often difficult for him, he was easily confused about what was required of him and exhausted much of the day. Logging in to a computer was much too hard for him and driving was initially impossible. Brian had become very vulnerable and emotional often weeping with fear and frustration at his inability to move on with his life.

I read as much as I could about rhabdomyolysis and muscle damage. We changed our diet to include far more vegetables, eliminated processed foods and reduced carbohydrates and under medical advice from overseas doctors I included – CoQ10, Omega 3, and magnesium.

I was also really concerned to find thousands of others world wide had been damaged by statins. I had information from the Centre of Adverse Reactions in Dunedin in 2010 which said 11 people in NZ have died fromsimvastatin and there are over 30 reports of rhabdomyolysis  in their database. I didn’t ask about other statins. It is my belief that ACC and in general, the medical profession and pharmaceutical companies would prefer these statistics were not made public.

Compensation Quicksands

The first eight years after the adverse reaction were really hard for Brian and he has shown courage and determination to be the best he can. Many of the original symptoms from 2002 became more manageable but he still suffers from ongoing pain and is limited in his capacity to function fully in society. Until 2009 ACC was very supportive so we could concentrate on Brian’s rehabilitation.

However since 2009, ACC has continued to strive to ‘prove’ he didn’t have an adverse reaction to the statin or the symptoms from the statin injury are spent or most frustratingly that the symptoms are all age related or pre-existed 2002.

Over the next two years he was sent for assessment after assessment, in total around 15. Each assessment leaves him exhausted and traumatised. He was compelled to attend each appointment in order to preserve his entitlements with the ACC. Brian battled on and almost every specialist agreed with the original diagnosis. However it took just one report challenging the original diagnosis to determine that the effects of the injury were now spent. As a consequence Brian has now had his entitlements suspended.

This has directly impacted on our relationship and health. At times, both of us have felt we could not face one more day of this additional pressure. Brian’s nightmares and anxiety have become more regular and his speech and confidence in communicating with people has deteriorated as he has to endure the retelling of details of the original injury and subsequent illness to medical assessors contracted by ACC.

In 2012 we opted for Brian to have a muscle biopsy to ‘show’ he had long standing damage from the statin. The results did not show any mitochondrial damage but did show cell hypertrophy. The muscular skeletal specialist has explained that essentially the muscle cells which survived the rhabdomyolysis became super big and have contributed to the body wide discomfort.

Brian has also had a blood test to see if he had any genes that could predispose him to statin-induced myotoxicity. But he was negative for these tests.

Was it Needed?

To our knowledge Brian had no pre-existing health disorders, he didn’t have diabetes or any cardiovascular disease. But his father, mother and brother had all had heart attacks. So it is reasonable to assume that taking a statin to lower cholesterol would be just the thing for Brian. This is what the advertisements say. This is what the doctors say – at least the ones who haven’t read the impartial reports about cardiovascular disease and mortality.

It is strange then to think that Brian’s mother was on a statin but still had a heart attack.

His younger brother was on a statin for years and developed a heart problem and later had a heart attack and triple bypass and he is still on high doses of a statin. He has also developed diabetes.

Does Cholesterol Need to be Lowered?

Maybe lowering cholesterol isn’t the answer. Many well known doctors and researchers are bold enough to query the statistics provided by the pharmaceutical companies. And to their credit many doctors we have dealt with over the last 11 years have been very supportive and for that we would like to thank them.

Could it be that inflammation or other factors cause atherosclerosis? Is animal fat relevant? Does a diet full of processed foods affect our heart? Would we be better with a diet rich in olive oil and fish? Physicians, scientists and science writers are debating these issues. Having a debate about it is good. It’s a start. Our goal should be to reduce disease but not at the risk of damaging other parts of the body. Nobody should have to go through what we go through every day.

Persisting and unresolved damage from the statin injury has remained a problem for Brian, but we must also endure ongoing legal battles with ACC to ensure his Claimant Rights are being met.

There are still too many doctors and health professionals who are not willing to look at drug side effects, overall risk versus benefit and most importantly the need to remember the Hippocratic Oath: ‘I will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone.’

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Heather’s article originally appeared at RxISK.org. Clicking here will not only link to the original article but also comments by others who suffered serious health issues after being prescribed statin drugs.

You can also report a drug side effect and get a free RxISK Report here.

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Anthony Colpo is an independent researcher, physical conditioning specialist, and author of The Fat Loss Bibleand The Great Cholesterol Con. For more information, visit TheFatLossBible.net orTheGreatCholesterolCon.com
Copyright © Anthony Colpo.
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