Statins associated with inflammation of the muscles

This study was published in the Journal of Clinical Rheumatology 2001 Oct;7(5):340-5

 

Study title and author:

A case of atorvastatin combined toxic myopathy and inflammatory myositis.

Folzenlogen D.

Department of Internal Medicine, Division of Immunology and Rheumatology, University of Missouri, MA 425, One Hospital Drive, Columbia, MO 65212, USA.

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17039167

This paper reports the case of a 76-year-old male patient undergoing statin therapy.

(i) The patient had elevations of muscle enzymes and was diagnosed with inflammatory polymyositis (chronic inflammation of the muscles) combined with statin toxic myopathy (muscle disease).
(ii) His symptoms and enzyme abnormalities resolved with the removal of the statin medication.

This case highlights the association between statins and inflammation of the muscles.

Statins inflame and destroy blood vessels

This paper was published in Clinical Rheumatology 2008 Dec;27 Suppl 2:S75-7

Study title and authors:
A case of ANCA-associated systemic vasculitis induced by atorvastatin.

Haroon M, Devlin J.
Department of Rheumatology, Waterford Regional Hospital, Waterford, Republic of Ireland. mharoon301@hotmail.com

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/18839266

Vasculitis is a group of disorders that destroy blood vessels by inflammation. ANCA-associated vasculitides are diseases caused by vasculitis in which antineutrophil cytoplasmic antibodies (ANCAs) can be detected in the blood.

This paper reports a case of statin induced ANCA-associated vasculitides.

(i)  A 45-year-old male patient reported to an Accident and Emergency department with a six week history of pain and stiffness involving his legs. Both calves were markedly tender, and he was not able to bear weight.
(ii) He also complained of numbness involving his left big toe for a few days, which later spread to involve his arms, and tinnitus and hearing loss in his left ear.
(iii) He had been taking atorvastatin 10 mg for six months.
(iv) Investigations showed markedly increased inflammatory markers, markedly increased antineutrophil cytoplasmic antibody (ANCA) levels and muscle damage.
(v) A diagnosis of statin-induced ANCA-associated vasculitis and statin-induced distal myopathy (muscle disease) was made.
(vi) The patients symptoms and laboratory abnormalities resolved rapidly after cessation of the statin drug and implementation of treatment.

This case shows the association between statins and ANCA-associated vasculitis. 

Statin treatment associated with significant muscle mitochondrial DNA depletion

This study was published in Clinical Pharmacology and Therapeutics 2007 May;81(5):650-3

Study title and authors:
Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin.

Schick BA, Laaksonen R, Frohlich JJ, Päivä H, Lehtimäki T, Humphries KH, Côté HC.
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada, and Research Unit, Tampere University Hospital, Finland.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17329991

Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation. Oxidative phosphorylation is a process that uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source.

Any depletion of muscle mitochondrial DNA may lead to muscle weakness and/or liver failure, and more rarely, brain abnormalities. “Floppiness,” feeding difficulties and developmental delays are common symptoms.

The aim of this study was to determine whether muscle mitochondrial DNA levels are altered during statin therapy. This clinical trial included 43 patients, aged 31 to 69 years, who had their levels of muscle mitochondrial DNA measured at the start of the study and again after eight weeks. The subjects were placed into three groups:
(i) Simvastatin 80 mg per day.
(ii) Atorvastatin 40 mg per day.
(iii) Placebo.

The study found:
(a) A significant decrease in muscle mitochondrial DNA levels was observed in the simvastatin group and a smaller decrease in levels in the atorvastatin group.
(b) Half the patients in the simvastatin group had a greater than 50% decrease in muscle mitochondrial DNA levels.
(c) 13% of the patients in the atorvastatin group had a greater than 50% decrease in muscle mitochondrial DNA levels.

The study shows that statin treatment may be associated with significant muscle mitochondrial DNA depletion.

The researchers conclude: "Given that statin therapy is often life-long, the large decrease (47%) observed raises concern about the potential longterm effect of statins on mitochondrial DNA and skeletal muscle mitochondria".

Statins exacerbate exercise-induced skeletal muscle injury

This study was published in Metabolism 1997 Oct;46(10):1206-10

 

Study title and authors:

Lovastatin increases exercise-induced skeletal muscle injury.

Thompson PD, Zmuda JM, Domalik LJ, Zimet RJ, Staggers J, Guyton JR.

Division of Cardiology, University of Pittsburgh, PA, USA.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/9322808

This study investigated the association between statins, exercise and creatine kinase levels (high levels of creatine kinase are a marker for muscle damage) using a double-blind, placebo-controlled design. The study include 59 healthy men aged 18 to 65 years who were assigned to receive lovastatin (40 mg per day) or placebo for 5 weeks. The men completed 45 minutes of treadmill walking after 4 weeks of treatment.

The study found that the creatine kinase levels of the men who received lovastatin were 62% and 77% higher 24 and 48 hours after the treadmill exercise compared to the men who received placebo.

The researchers concluded that statins exacerbate exercise-induced skeletal muscle injury.

Statins increase the risk of chronic muscle diseases by 286%

This study was published in the Annals of the Rheumatic Diseases 2008 May;67(5):614-9

 

Study title and authors:

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. sailler.l@chu-toulouse.fr

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17768174

This study evaluated the association between chronic muscle diseases and prior exposure to cholesterol lowering drugs. The study, which lasted for two years, included 37 patients with chronic muscle diseases such as dermatomyositis and polymyositis who were compared to 185 control subjects.

The study found that those who were exposured to statins had a 286% increased risk of dermatomyositis and polymyositis.

Statins increase the risk of muscle adverse reactions

This study was published in Muscle and Nerve 2011 Dec;44(6):877-81

Study title and authors:
Prevalence and risk factors of muscle complications secondary to statins.

El-Salem K, Ababneh B, Rudnicki S, Malkawi A, Alrefai A, Khader Y, Saadeh R, Saydam M.
Department of Neurosciences, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan. khalidelsalem@hotmail.com

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22102457

The aim of the study was to investigate the prevalence of muscle complications among patients using statins. The study included 345 patients receiving statins who were compared with an age- and gender-matched control group of 85 nonusers.

The study found that statin users had a 256% increased risk of muscle adverse reactions compared to nonusers.

Analysis of 119 statin randomized controlled trials find that statins increase the risk of muscle problems

This study was published in Pharmacoepidemiology and Drug Safety 2007 Feb;16(2):132-43

 

Study title and authors:

Systematic review and meta-analysis of clinically relevant adverse events from HMG CoA reductase inhibitor trials worldwide from 1982 to present.

McClure DL, Valuck RJ, Glanz M, Hokanson JE.

Kaiser Foundation Health Plan of Colorado, Clinical Research Unit, Denver, CO 80237-8066, USA. david.l.mcclure@kp.org

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17072896

The objective of the study was to determine the association of adverse events from a systematic review and meta-analysis of statin randomized controlled trials. The study included over 86,000 participants from 119 studies.

The study found:
(a) Statin users had a 59% increased risk of rhabdomyolysis (the breakdown of muscle fibers that leads to the release of muscle fiber contents into the bloodstream and often causes kidney damage) compared to nonusers.
(b) Statin users had a 156% increased risk of myositis (inflammation of the muscles) compared to nonusers.
(c) Statin users had a 9% increased risk of myalgia (muscle pain) compared to nonusers.

This analysis of 119 statin randomized controlled trials found that statins increased the risk of muscle problems.

Statins are associated with an approximate doubling of the risk of muscle disease

This study was published in Clinical Therapeutics 2007 Aug;29(8):1761-70

Study title and authors:
Does statin therapy initiation increase the risk for myopathy? An observational study of 32,225 diabetic and nondiabetic patients.

Nichols GA, Koro CE.
Kaiser Permanente, Center for Health Research, Portland, Oregon 97227-1098, USA. greg.nichols@kpchr.org

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17919557

The objective of this study was to determine the prevalence of myopathy (muscle disease) among subjects with or without diabetes, some of whom received statin treatment. the study included 32,225 subjects who were followed for nine years.

The study found:
(a) Statins users with diabetes had a 43% increased risk of myopathy compared to non-users with diabetes.
(b) Statin users without diabetes had a 143% increased risk of myopathy compared to non-users without diabetes.

The study reveals that statins are associated with an approximate doubling of the risk of muscle disease.

Statins increase the risk of muscle pain by 90%

This study was published in Circulation 2012 Nov 26

 

Study title and authors:

The Effect of Statins on Skeletal Muscle Function.

Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J, Chipkin S, Pescatello LS, Simpson K, White CM, Thompson PD.

1 Hartford Hospital, Hartford, CT;

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/23183941

This study assessed the effects of statins on muscle function. The study included 420 healthy subjects, who had never previously taken statins, who received either 80 mg of atorvastatin or placebo for six months.

The study found:
(a) The creatine kinase levels of those who received statins increased by 20.8 U/L. (The appearance of creatine kinase in blood has been generally considered to be an indirect marker of muscle damage).
(b) Those who received statins had a 90% increased risk of muscle pain compared to those who received placebo.

The results of this trial show that statins increase the risk of muscle injury.

Statins impair energy production and promote muscle damage

This study was published in Muscle and Nerve 2011 Jan;43(1):76-81

Study title and authors:
Evaluation of skeletal muscle during calf exercise by 31-phosphorus magnetic resonance spectroscopy in patients on statin medications.

Wu JS, Buettner C, Smithline H, Ngo LH, Greenman RL.
Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. jswu@bidmc.harvard.edu

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21171098

Phosphocreatine is a substance that is fundamental to the ability of the body to produce muscular energy.

Elevated blood levels of creatine kinase are indicative of muscle damage.

The study investigated the association of statin treatment on recovery from exercise. The study included ten patients, (who were subject to a four-week regimen of statin therapy), who had their phosphocreatine and creatine kinase levels measured pre- and post-statin therapy.

The study found:
(a) Phosphocreatine levels took 97% longer to recover from exercise after statin therapy.
(b) Creatine kinase levels rose by 17.7% after statin therapy.

The results of the study suggest that statin therapy may impair energy production and promote muscle damage.

Statins increase the risk of musculoskeletal pain

This study was published in the American Journal of Medicine 2012 Feb;125(2):176-82

Study title and authors:
Statin use and musculoskeletal pain among adults with and without arthritis.

Buettner C, Rippberger MJ, Smith JK, Leveille SG, Davis RB, Mittleman MA.
Harvard Medical School, Boston, MA, USA. cbuettne@bidmc.harvard.edu

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22269621

This study investigated the relationship between statin use and musculoskeletal pain. (The musculoskeletal system is made up of the body's bones (the skeleton), muscles, cartilage, tendons, ligaments, joints, and other connective tissue that supports and binds tissues and organs together). The study included 8,228 adults aged 40 years or more.

The study found those taking statins had a 15% increased risk of musculoskeletal pain compared to non-users.

After only six months of therapy with a statin (Zocor), nearly a quarter of the patients suffered from side effects

This study was published in the New Zealand Medical Journal 1991 Nov 27;104(924):493-5

Study title and authors:

Simvastatin and side effects.

Scott RS, Lintott CJ, Wilson MJ.

Princess Margaret Hospital, Christchurch.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/1745460

The object of the study was to investigate the side effects of simvastatin (Zocor). The study included 110 patients newly commenced on simvastatin who completed a side effects questionnaire after six months of therapy.

The study found:
(a) 23.6% of patients suffered side effects.
(b) 13.6% of patients suffered muscle aches.
(c) 4.5% of patients suffered gastrointestinal symptoms.

After only six months of therapy with a statin (Zocor), nearly a quarter of the patients suffered from side effects.

The unintended adverse effects of statins in men and women

This study was published in the British Medical Journal 2010 May 20;340:c2197

Study title and authors:
Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database.

Hippisley-Cox J, Coupland C.
Division of Primary Care, University Park, Nottingham NG2 7RD. julia.hippisley-cox@ntlworld.com

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/20488911

The objective of the study was to quantify the unintended effects of statins. The study included 2,004 692 patients aged 30-84 years.

The study found after five years:
(a) Women who used statins had a 56% increased risk of acute renal (kidney) failure compared to women who did not use statins.
(b) Women who used statins had a 30% increased risk of cataracts compared to women who did not use statins.
(c) Women who used statins had a 53% increased risk of liver disease compared to women who did not use statins.
(d) Women who used statins had a 197% increased risk of myopathy (muscle disease) compared to women who did not use statins.
(e) Men who used statins had a 61% increased risk of acute renal (kidney) failure compared to men who did not use statins.
(f) Men who used statins had a 32% increased risk of cataracts compared to men who did not use statins.
(g) Men who used statins had a 53% increased risk of liver disease compared to men who did not use statins.
(h) Men who used statins had a 515% increased risk of myopathy (muscle disease) compared to men who did not use statins.

The study highlights some of the unintended adverse effects of using statins.
Statins increase the death rate by 150-300%
Statins increase the incidence of liver damage
Statin use increases muscle damage after exercise (including the heart muscle)