Congenital abnormalities in baby born to mother using lovastatin

Thursday, 10 March 2016

Congenital abnormalities in baby born to mother using lovastatin

This study was published in the Lancet 1992 Jun 6;339(8806):1416-7

Study title and authors:
Congenital abnormalities (VATER) in baby born to mother using lovastatin.

Ghidini A, Sicherer S, Willner J.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/1350826

This paper reports the case of an infant born with many malformations after the mother used a statin during pregnancy.

(i) A woman was treated for five weeks with lovastatin, starting approximately six weeks from her last menstrual period.
(ii) The statin was discontinued when her pregnancy was diagnosed at 11 weeks' gestation.
(iii) A female infant was delivered by cesarean section at 39 weeks' gestation. The infant had a constellation of malformations termed the VATER association (vertebral anomalies, anus not developed properly, an abnormal connection between the oesophagus and the trachea with part of the oesophagus missing, and kidney, forearm and wrist abnormalities).
(iv) Her anomalies included a deformed chest, spinal deformity, absent left thumb, foreshortened left forearm, shortened left elbow, fusion of the ribs on the left, anomalies in the spine, deformed left forearm, and a narrow lower oesophagus.

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.

Important safety label changes to cholesterol-lowering statin drugs

FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs

Facts about statins

A class of prescription drugs used together with diet and exercise to reduce blood levels of low-density lipoprotein (LDL) cholesterol (“bad cholesterol”) Marketed as single-ingredient products, including Lipitor (atorvastatin), Lescol (fluvastatin), Mevacor (lovastatin), Altoprev (lovastatin extended-release), Livalo (pitavastatin), Pravachol (pravastatin), Crestor (rosuvastatin), and Zocor (simvastatin) Also marketed as combination products, including Advicor (lovastatin/niacin extended-release), Simcor (simvastatin/niacin extended-release), and Vytorin (simvastatin/ezetimibe)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Safety Announcement

[2-28-2012] The U.S. Food and Drug Administration (FDA) has approved important safety label changes for the class of cholesterol-lowering drugs known as statins. These changes were made to provide the public with more information for the safe and effective use of statins and are based on FDA’s comprehensive review of the statin class of drugs (see Data Summary below). The changes include the following:

Infographic About Cholesterol and Statins1 2

Monitoring Liver Enzymes
Labels have been revised to remove the need for routine periodic monitoring of liver enzymes in patients taking statins. The labels now recommend that liver enzyme tests should be performed before starting statin therapy and as clinically indicated thereafter. FDA has concluded that serious liver injury with statins is rare and unpredictable in individual patients, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.

Adverse Event Information
Information about the potential for generally non-serious and reversible cognitive side effects (memory loss, confusion, etc.) and reports of increased blood sugar and glycosylated hemoglobin (HbA1c) levels has been added to the statin labels. FDA continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.

Drug Interactions
The lovastatin label has been extensively updated with new contraindications (situations when the drug should not be used) and dose limitations when it is taken with certain medicines that can increase the risk for muscle injury (see Lovastatin Dose Limitations below).

Healthcare professionals should refer to the drug labels for the latest recommendations for prescribing statins (also see Additional Information for Healthcare Professionals below). Patients should contact their healthcare professional if they have any questions or concerns about statins.

Additional Information for Patients

• The statin drug labels have been revised to provide patients with more information on the safe and effective use of statins. Patients should be aware of the following information:
  • There have been rare reports of serious liver problems in patients taking statins. Patients should notify their healthcare professional right away if they have the following symptoms: unusual fatigue or weakness; loss of appetite; upper belly pain; dark-colored urine; or yellowing of the skin or the whites of the eyes.
  • Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken.
  • Increases in blood sugar levels have been reported with statin use.
  • Certain medicines should never be taken (are contraindicated) with lovastatin (Mevacor) (see Lovastatin Dose Limitations below).
• Patients should contact their healthcare professional if they have any questions or concerns about statins.
• Patients should report side effects from the use of statins to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of the page.
  

Additional Information for Healthcare Professionals

• Healthcare professionals should perform liver enzyme tests before initiating statin therapy in patients and as clinically indicated thereafter. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, therapy should be interrupted. If an alternate etiology is not found, the statin should not be restarted.
• There have been rare post-marketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These reported symptoms are generally not serious and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
• Increases in glycosylated hemoglobin (HbA1c) and fasting serum glucose levels have been reported with statin use.
• Healthcare professionals should follow the recommendations in the lovastatin label regarding drugs that may increase the risk of myopathy/rhabdomyolysis when used with lovastatin (see Lovastatin Dose Limitations below).
• Healthcare professionals should report adverse events involving statins to the FDA MedWatch program using the information in the "Contact FDA" box at the bottom of this page.
  

Data Summary

Removal of routine monitoring of liver enzymes from drug labels

FDA reviewed current monitoring guidelines, including the National Lipid Association’s Liver Expert Panel and Statin Safety Task Force recommendations.^{1, 2} The Liver Expert Panel stated that the available scientific evidence does not support the routine monitoring of liver biochemistries in asymptomatic patients receiving statins. The Panel made this recommendation because (1) irreversible liver damage resulting from statins is exceptionally rare and is likely idiosyncratic in nature, and (2) no data exist to show that routine periodic monitoring of liver biochemistries is effective in identifying the very rare individual who may develop significant liver injury from ongoing statin therapy. The Panel believed that routine periodic monitoring will instead identify patients with isolated increased aminotransferase levels, which could motivate physicians to alter or discontinue statin therapy, thereby placing patients at increased risk for cardiovascular events.¹ The National Lipid Association’s Statin Task Force also stated that routine monitoring of liver function tests is not supported by the available evidence.²

FDA reviewed post-marketing data to evaluate the risk of clinically serious hepatotoxicity associated with statins. FDA had conducted several post-marketing reviews of statins and hepatotoxicity between years 2000 and 2009 by searching the Agency’s Adverse Event Reporting System (AERS) database. Those reviews consistently noted that reporting of statin-associated serious liver injury to the AERS database was extremely low (reporting rate of ≤2 per one million patient-years). FDA’s updated review focused on cases of severe liver injury, defined as a 4 (severe liver injury) or a 5 (death or liver transplant) using the Drug Induced Liver Injury Network (DILIN) liver injury severity scale, which were reported to AERS from marketing of each statin through 2009. Cases meeting those criteria were further assessed for causality. Seventy-five cases (27 cases with a severity score of 4, and 48 cases with a severity score of 5 (37 deaths and 11 liver transplants) were assessed for causality. Thirty of the 75 cases (14 deaths, 7 liver transplantations, and 9 severe liver injury) were assessed as possibly or probably associated with statin therapy. No cases were assessed as highly likely or definitely associated with statin therapy. FDA concluded that, despite a rising use of statins as a class since the late 1990s, there has not been a detectable increase in the annual rates of fatal or severe liver injury cases possibly or probably causally associated with statin use.

FDA also reviewed cases from the DILIN and Acute Liver Failure Study Group (ALFSG), organizations that have been submitting reports to FDA of drug-associated liver injury in their liver injury outcome studies. As of January 1, 2011, DILIN had submitted 25 reports of statin-associated liver injury to FDA, 12 of which gave hospitalization as an outcome. A 2010 article from ALFSG included 133 prospectively identified cases of idiopathic drug-induced liver injury resulting in acute liver failure.³ Of these 133 patients, 15 were taking statins, and in six of these 15 individuals a statin was identified as the only potential drug to cause drug-induced liver injury.

Based on all available data, FDA has determined that all currently marketed statins appear to be associated with a very low risk of serious liver injury and that routine periodic monitoring of serum alanine aminotransferase (ALT) does not appear to detect or prevent serious liver injury in association with statins.

Cognitive adverse events

FDA reviewed the AERS database, the published medical literature (case reports and observational studies),^4-13 and randomized clinical trials to evaluate the effect of statins on cognition.^14-17

The post-marketing adverse event reports generally described individuals over the age of 50 years who experienced notable, but ill-defined memory loss or impairment that was reversible upon discontinuation of statin therapy. Time to onset of the event was highly variable, ranging from one day to years after statin exposure. The cases did not appear to be associated with fixed or progressive dementia, such as Alzheimer’s disease. The review did not reveal an association between the adverse event and the specific statin, the age of the individual, the statin dose, or concomitant medication use.

Data from the observational studies and clinical trials did not suggest that cognitive changes associated with statin use are common or lead to clinically significant cognitive decline.

Increases in glycosylated hemoglobin (HbA1c) and fasting plasma glucose

FDA’s review of the results from the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) reported a 27% increase in investigator-reported diabetes mellitus in rosuvastatin-treated patients compared to placebo-treated patients. High-dose atorvastatin had also been associated with worsening glycemic control in the Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) substudy.¹⁸

FDA also reviewed the published medical literature.^19-26 A meta-analysis by Sattar et al.,19 which included 13 statin trials with 91,140 participants, reported that statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.02-1.17), with little heterogeneity (I2=11%) between trials. A meta-analysis by Rajpathak et al.,²⁰ which included 6 statin trials with 57,593 participants, also reported a small increase in diabetes risk (relative risk [RR] 1.13; 95% CI 1.03-1.23), with no evidence of heterogeneity across trials. A recent study by Culver et al.,²⁶ using data from the Women’s Health Initiative, reported that statin use conveys an increased risk of new-onset diabetes in postmenopausal women, and noted that the effect appears to be a medication class effect, unrelated to potency or to individual statin.

Based on clinical trial meta-analyses and epidemiological data from the published literature, information concerning an effect of statins on incident diabetes and increases in HbA1c and/or fasting plasma glucose was added to statin labels.

Lovastatin drug-drug interactions

Information regarding drug-drug interactions and contraindications and dose limitations has been added to the lovastatin label. Subsequent to the June 2011 label revisions to the simvastatin-containing products, which were based largely on the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial,²⁷ a review of drug-drug interactions with lovastatin was conducted because the physicochemical and pharmacokinetic properties of lovastatin are comparable to those of simvastatin.

Lovastatin is a sensitive in vivo cytochrome P450 3A4 (CYP3A4) substrate. Strong CYP3A4 inhibitors are predicted to significantly increase lovastatin exposure. A literature review indicates that itraconazole, a strong CYP3A4 inhibitor, increases lovastatin exposure up to 20-fold and the drug interaction appears to result in rhabdomyolysis.²⁸ The effect of itraconazole on lovastatin exposure can therefore be extrapolated to other strong CYP3A4 inhibitors, including ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, human immunodeficiency virus (HIV) protease inhibitors, boceprevir, telaprevir, and nefazodone.

Lovastatin Dose Limitations

Previous lovastatin label	New lovastatin label
Avoid lovastatin with: Itraconazole Ketoconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Nefazodone	Contraindicated with lovastatin: Itraconazole Ketoconazole Posaconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Boceprevir Telaprevir Nefazodone
Do not exceed 20 mg lovastatin daily with: Gemfibrozil Other fibrates Lipid-lowering doses (≥1 g/day) of niacin Cyclosporine Danazol	Avoid with lovastatin: Cyclosporine Gemfibrozil
	Do not exceed 20 mg lovastatin daily with: Danazol Diltiazem Verapamil
Do not exceed 40 mg lovastatin daily with: Amiodarone Verapamil	Do not exceed 40 mg lovastatin daily with: Amiodarone
Avoid large quantities of grapefruit juice (>1 quart daily)	Avoid large quantities of grapefruit juice (>1 quart daily)

References

1. Cohen DE, Anania FA, Chalasani N; for the National Lipid Association Statin Safety Task Force Liver Expert Panel. An assessment of statin safety by hepatologists. Am J Cardiol. 2006;97(8A):77C-81C.
2. McKenney JM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006;97(8A):89C-94C.
3. Reuben A, Koch DG, Lee WM; for the Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065-2076.
4. Orsi A, Sherman O, Woldeselassie Z. Simvastatin-associated memory loss. Pharmacotherapy. 2001;21:767-9.
5. Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy. 2003;23:871-80.
6. Evans MA, Golomb BA. Statin-associated adverse cognitive effects: survey results from 171 patients. Pharmacotherapy. 2009;29:800-811.
7. Parker BA, Polk DM, Rabdiya V, et al. Changes in memory function and neuronal activation associated with atorvastatin therapy. Pharmacotherapy. 2010;30(6):236e-240e.
8. Zamrini E, McGwin G, Roseman JM. Association between statin use and Alzheimer's disease. Neuroepidemiology. 2004;23:94-98.
9. Zandi PP, Sparks DL, Khachaturian AS, et al. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry. 2005;62:217-224.
10. Zhou B, Teramukai S, Fukushima M. Prevention and treatment of dementia or Alzheimer's disease by statins: a meta-analysis. Dement Geriatr Cogn Disord. 2007;23:194-201.
11. Beydoun MA, Beason-Held LL, Kitner-Triolo MH, et al. Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. J Epidemiol Community Health. 2011;65:949-957.
12. Bettermann K, Arnold AM, Williamson J, et al. Statins, risk of dementia, and cognitive function: secondary analysis of the Ginkgo Evaluation of Memory Study. J Stroke Cerebrovasc Dis. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2010.11.002³. Accessed January 31, 2012.
13. Benito-León J, Louis ED, Vega S, Bermejo-Pareja F. Statins and cognitive functioning in the elderly: a population-based study. J Alzheimers Dis. 2010;21:95-102.
14. Muldoon MF, Barger SD, Ryan CM, et al. Effects of lovastatin on cognitive function and psychological well-being. Am J Med. 2000;108:538-546.
15. Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am J Med. 2004;117:823-829.
16. Trompet S, van Vliet P, de Craen AJ, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol. 2010;257:85-90.
17. Feldman HH, Doody RS, Kivipelto M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74:956-964.
18. Sabatine MS, Wiviott SD, Morrow DA, McCabe CH, Cannon CP. High-dose atorvastatin associated with worse glycemic control: a PROVE-IT TIMI 22 substudy. Circulation. 2004;110(Suppl I):S834.
19. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-742.
20. Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32(10):1924-1929.
21. Sukhija R, Prayaga S, Marashdeh M, et al. Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Investig Med. 2009;57:495-499.
22. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol. 2010;55:1209-1216.
23. Thongtang N, Ai M, Otokozawa S, et al. Effects of maximal atorvastatin and rosuvastatin treatment on markers of glucose homeostasis and inflammation. Am J Cardiol. 2011;107:387-392.
24. Kostapanos MS, Liamis GL, Milionis HJ, Elisaf MS. Do statins beneficially or adversely affect glucose homeostasis? Curr Vasc Pharmacol. 2010;8:612-631.
25. Mills EJ, Wu P, Chong G, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM. 2011;104:109-124.
26. Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med. 2012;172(2):144-152.
27. Armitage J, Bowman L, Wallendszus K; for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. , et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376:1658-1669.
28. Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med. 1995;333:664-555.

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Read the complete article here.

Professional athletes...rarely tolerate statin treatment because of muscular problems

Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems

Abstract

 

Aims

Muscular problems are the major group of side-effects during statin treatment. They are known to occur much more frequently during and after exercise.

 

Methods and results

For the last 8 years we have monitored 22 professional athletes in whom, because of familial hypercholesterolaemia, treatment with different statins was attempted. Only six out of the 22 finally tolerated at least one member of this family of drugs. In three of these six the first statin prescribed allowed training performance without any limitation. Changing the drug demonstrated that only two tolerated all the four or five statins examined (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin). Cerivastatin was not among the statins prescribed.

 

Conclusions

These findings indicate that in top sports performers only about 20% tolerate statin treatment without side-effects. Clinical decision making as to lipid lowering therapy thus becomes a critical issue in this small subgroup of patients.

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 Read the full article here.

Statin Associated Myopathy and Exercise

Statin Associated Myopathy and Exercise

By Dr. Duane Graveline, M.D., M.P.H.
Not only can statin drugs cause myopathy ( muscle disease ) of varying degrees but this myopathy is greatly exacerbated by exercise. ( Ref 1 ). The effect of exercise is such that most experienced athletes will not use statins for fear of predisposition to muscle side effects of all kinds.

The severity of the muscle side effects from statins vary widely from relatively benign CPK elevation without symptoms, to muscle tenderness, aching, soreness and pain, and rarely, even to death from rhabdomyolysis.
The existing literature is lacking as to definite identification of mechanisms but a number of potential mechanisms include:
1. Induction of skeletal muscle fiber apoptosis ( cellular death, the usual result of accumulation of sufficient mitochondrial DNA mutations so the cell is taken out of service, so to speak ).
2. Alterations in ubiquitin-proteasome pathway activity ( a cellular system that identifies and degrades proteins ) leading to mitochondrial dysfunction ( the ultimate effect of CoQ10 inhibition secondary to mevalonate blockade ).
3. Terpenoid depletion ( consequence of dolichol inhibition and aberration in glycoprotein synthesis ).

These three pathways are also considered to be the primary channels by which we age - mitochondrial damage, CoQ10 depletion and dolichol inhibition. Additionally, I suspect that these three pathways that explain statin drug effects on muscle cells are the same for damage to other cell types as well.

Ten years ago an internet search would have come up with little to nothing on the subject of statin associated myopathy pathways but now the general pathophysiology has been defined by the many studies now in progress.

A major problem at present is that although these pathways are now well known to the research community, the clinical community of doctors is mostly lacking in the knowledge of even the basics of this statin effect and the very idea that statin damage uses the same pathways as aging is particularly difficult for clinicians to conceive.

The very idea that deficiency of this quaint supplement, CoQ10, is now considered by researchers to be a major foundation of statin damage and that many alternative medicine physicians are now far ahead of "regular doctors" in both their understanding and treatment of statin damage is particularly galling.

Dysfunction of the so called ubiquitin-proteasome pathway is a fancy way of saying CoQ10 inhibition, clearly defined in my first book, Lipitor®, Thief of Memory, years ago. What this refers to is the two-pronged statin attack on our mitochondria: first blocking the vital anti-oxidant role of CoQ10 and next blocking uptake of CoQ10 into the structure of complexes 1 and 2, major elements of electron transfer and ATP production. This occurs in every cell of our bodies.
It is difficult to understand how the developers of statins failed to recognize this potential, inevitable effect of compactin ( Mevastatin ) and lovastatin ( Mevacor ) the first statin drugs. The effect is there for all to see. What researchers are saying today had to have been clear to the original makers of statins. 

Next on this list of statin damage mechanisms currently reported by the research community is the consequence of terpenoid depletion. This is a fancy way of saying dolichol inhibition, additional collateral damage from mevalonate blockade. Remember, statin drugs are reductase inhibitors. To achieve reduction of cholesterol synthesis they have blocked the mevalonate pathway, inevitably blocking CoQ10 and dolichols ( and many other vital biochemicals as well ).

If the full range of CoQ10 deficiency on cellular function is difficult to accept, that of dolichols is nearly impossible for most clinicians since they have barely been introduced. Dolichols orchestrate the entire process of glycoprotein synthesis, the linkage of peptide fragments and certain sugars so the resulting strand not only determines our very emotionality but also cellular identity, communication and immunodefense. Without at least some basic understanding of dolichol biochemistry the possible effects of statins become unimaginable.

Not only do these processes of apoptosis, CoQ10 mediated mitochondrial damage and dolichol mediated glycoprotein dysfunction help to explain the full range of effects seen with statin myopathy but this same group of factors is involved in all other types of statin damage.

What we have found to be true as the underlying mechanism of statin injury to muscle cells is true for every other cell in our bodies as well. As to the aggravation of statin muscle damage from exercise, the ubiquitin-proteasome pathway in particular addresses this CoQ10 mandated process. When one's CoQ10 is at a minimal level, the slightest exercise is bound to aggravate.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

April 2011
1. http://www.ncbi.nlm.nih.gov/pubmed/20878737

Dangers of Statin Drugs - Time Magazine article

Note added July 18, 2010 - Time Magazine seems to have removed the article titled "Dangers of Statin Drugs" mentioned in this blog post from their web site. Just goes to show that MSM is not really about to give any credence to other than the mainstream view of CVD and statin drug use.

Please read this very good article on the dangers of Atorvastatin, Lovastatin, Rosuvastatin, Simvastatin etc. Also known by more common names Lipitor, Mevacor, Crestor, Zocor, Vytorin. Note this is not a complete list of statin drugs. Cerivistatin or Baycol was pulled because too many people died from taking it (the ultimate side effect).

NOTE: I removed the link to the Time article because they removed the original article which I referred to and substituted another.
Here is a link to a blog that has a copy of the article you can read.

Stopped Our Statins - A Yahoo group

Having trouble dealing with your doctor about cholesterol and statin side effects?

Join this Yahoo Group and see how others handle it and read about their experiences.










Here's what they say:

Stopped Our Statins is for those experiencing AE's (adverse effects) to statins: Advicor(Niacin Extended-Release & Lovastatin), NEW ~ Caduet (Lipitor & Norvasc), Crestor(Rosuvastatin),Lipitor(Atorvastatin),Lescol(Fluvastatin), Mevacor(Lovastatin), Pravachol(Pravastatin), Zocor(Simvastatin),Vytorin(Ezetimibe-Simvastatin) & Baycol(Cerivastatin). Baycol, causing over 100 deaths & 11,000 cases of severe side effects, was removed from the market 8/01.