Hepatitis, rhabdomyolysis and multi-organ failure resulting from statin use

This paper was published in the British Medical Journal Case Reports 2009;2009. pii: bcr07.2008.0412

Study title and authors:
Hepatitis, rhabdomyolysis and multi-organ failure resulting from statin use.

Rajaram M.
St Helens and Knowsley Hospitals NHS Trust, Medicine-Gastro, Whiston Hospital, Warrington Prescot, L35 5DR, UK.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21686823

This paper reports the case of of a woman who developed hepatitis, rhabdomyolysis and multi-organ failure resulting from the use of statins.

(i) A 77-year-old female patient was admitted to hospital with malaise, anorexia and generally feeling unwell for a week.
(ii) She was taking atorvastatin 80 mg daily.
(iii) The dose of atorvastatin was increased from 40 mg to 80 mg daily approximately six months before admission.
(iv) Examination revealed she was jaundiced.
(v) Laboratory tests revealed the following abnormalities (normal levels in brackets):
Creatine kinase: 523 iu/l (25–200)
Lactate dehydrogenase: 1241 iu/l (240–525)
Total bilirubin: 284 μmol/l (2–22)
Alanine transaminase: 2314 iu/l (11–55)
γ glutamyl transferase: 132 iu/l (5–50)
Aspartate transaminase: 1269 iu/l (12–42)
Alkaline phosphatase: 438 iu/l (40–125)
Urea: 15.9 mmol/l (3.6–7.3)
Creatinine: 290μmol/l (45–110)
(vi) A diagnosis of hepatitis related to statin use with accompanying kidney failure was made.
(vii) The statin was stopped and her liver biochemistry improved.
(viii) However on the fourth day after admission, her kidney function deteriorated.
(ix) Examination revealed excess fluid around the lungs and abdominal areas.
(x) The patient was transferred to the intensive care unit and required haemofiltration. (Hemofiltration is a kidney replacement therapy similar to hemodialysis).
(xi) Despite improvement in her kidney function, the creatine kinase levels continued to rise and peaked at 107178 iu/l.
(xii) Two weeks after admission to the hospital, the patient died of multi-organ failure.

Rajaram concludes: "The cause of hepatitis, rhabdomyolysis, and acute renal failure in this patient was the increase in dose of atorvastatin and subsequent elevation of serum atorvastatin concentration. We suggest that the elevation of atorvastatin concentrations resulted in skeletal muscle damage and rhabdomyolysis, as indicated by the elevation of creatine kinase and subsequent deposition of myoglobin in the kidneys, causing acute renal failure as indicated by the elevation of urea and creatinine".

From a fish tank injury to hospital haemodialysis: the serious consequences of statin drug interactions

This paper was published in BMJ Case Reports 2015 Jun 23;2015

 

Study title and authors:

From a fish tank injury to hospital haemodialysis: the serious consequences of drug interactions.

Hill FJ, McCloskey SJ, Sheerin N.

Renal Department, Newcastle Upon Tyne Hospitals, Newcastle Upon Tyne, UK.

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26106178

This paper describes the case of a man who suffered acute kidney injury following statin-induced rhabdomyolysis.

(i) A 68-year-old man was admitted to hospital with severe acute kidney injury secondary to statin-induced rhabdomyolysis.
(ii) Five weeks previously, the patient started a course of clarithromycin for infection of a finger wound. His current medications included simvastatin, which he continued along with clarithromycin.
(iii) The severity of the acute kidney injury necessitated initial continuous venovenous haemofiltration followed by 12 haemodialysis sessions before a spontaneous improvement in renal function occurred.

Hill concluded: "Statins are widely prescribed and we report this case to encourage increased vigilance in avoiding drug interactions known to increase the risk of statin-induced myopathy, including macrolide antibiotics, calcium channel antagonists and amiodarone".

Rhabdomyolysis occurring under statins after intense physical activity in a marathon runner

This paper was published in Case Reports in Rheumatology 2015;2015:721078

Study title and authors:
Rhabdomyolysis Occurring under Statins after Intense Physical Activity in a Marathon Runner.

Toussirot É, Michel F, Meneveau N.
Clinical Investigation Center for Biotherapy, CIC-1431, FHU INCREASE, University Hospital of Besançon, 25000 Besançon, France

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25815236

This paper reports the case of a marathon runner who developed rhabdomyolysis.

(i) A 50 year old man healthy man started to take atorvastatin but soon suffered from severe muscle pain. He then was prescribed rosuvastatin.
(ii) The patient was a regular long-distance and marathon runner. He was preparing for an international competition.
(iii) On the day of the competition and while being still under rosuvastatin, the patient experienced progressively worsening muscular weakness. At the end of the race, he suffered from severe pains in the lower limbs similar to diffuse cramps associated with generalized muscle contraction.
(iv) Muscle enzymes (creatine kinase) were tested two days after the race and were at 2631 IU/L (normal levels 300) and he was diagnosed with rhabdomyolysis.
(v) One year later, (without taking the statins), for another marathon, the patient felt no muscle weakness at all or muscle contractions after the race.

Toussirot concluded: "Intense physical activity, as performed by statin treated athletes (whether professional or not and particularly during long-distance races) could have adverse consequences on muscles".

Statins with pomegranate juice may increase the risk of rhabdomyolysis

This study was published in the American Journal of Cardiology 2006 Sep 1;98(5):705-6

Study title and authors:
Rhabdomyolysis associated with pomegranate juice consumption.

Sorokin AV, Duncan B, Panetta R, Thompson PD.
Section of Preventive Cardiology, Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, Connecticut, USA.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/16923466

This paper reports the case of a man who developed rhabdomyolysis after drinking pomegranate juice while taking statins.

(i) A 48-year-old man had been taking ezetimibe and rosuvastatin for 17 months.
(ii) Three weeks before admission to hospital, he began drinking pomegranate juice (200 ml twice weekly).
(iii) On admission he had thigh pain and elevated serum creatine kinase level (138,030 U/L, normal is less than 200 U/L) and was diagnosed with rhabdomyolysis.

Sorokin concludes: "This report suggests that pomegranate juice may increase the risk of rhabdomyolysis during rosuvastatin treatment".

Doctor says there is no evidence that statins are safe

This paper was published in the Canadian Medical Association Journal May 6: 2008

Study title and author:
Statins - Safe?
Dr Herbert H. Nehrlich

This paper can be accessed at: http://www.cmaj.ca/content/178/5/576.abstract/reply#content-block

Dr Nehrlich, a doctor from Australia, discusses the effects of statin drugs.

(i) Statins reduce the body's production of mevalonate through the suppression of a liver enzyme called hydroxymethylglutaryl (HMG) coenzyme A reductase.
(ii) This enzyme is crucial in enabling the body to synthesize such substances as cholesterol, Co-enzyme Q-10 etc., substances that are essential for every living cell.
(iii) So, if you reduce the supply of mevalonate, the liver can no longer keep up production of sufficient cholesterol and has to slow the shipping of cholesterol from the depot (liver) to the various areas in need of it via the bloodstream. Hence, blood cholesterol will be lower in lab tests.
(iv) Mevalonate is not just important in this respect but is heavily involved in muscle metabolism as well as in the production of thromboxane. Thromboxane, of course, is the agent responsible for the important stage in healing called clotting and originates in the platelets of our blood.
(v) Mitochondria are energy factories that MUST have coenzyme Q- 10, the very substance that is in short supply when people undergo statin treatment.
(vi) The dismal success record of statin treatment, combined with their sometimes atrocious side effects (identified and hidden) makes the prescription of statins in humans an assault with unknown and likely dire consequences.
(vii) People tend to die with low cholesterol blood levels.
(viii) May I ask for the studies that have shown that lowering cholesterol is reasonable and thus good practice? Statins are safe? Let us look at the PROSPER Trial and the all cause mortality. It is not improved by statins.
(ix) I prefer to see cholesterol as an extremely vital substance, essential for good health and indispensable when it comes to repair and maintenance of the body.
(x) Statins are now Big Pharma's golden goose and the price of gold is rising.
(xi) If we think of rhabdomyolysis, of transient global amnesia and of the propensity of statins to initiate cancer in many animals, if we consider the truly dismal success of statin treatment then we can skip looking at the plausibility of using these drugs altogether.
(xii) Statins are mayhem to Coenzyme Q-10 and it follows that statins may thus weaken the heart. They may cause cancer in humans.

Dr Nehrlich concludes: "There is no evidence that statins are safe".

Statin and NSAID drugs lead to the death of a patient from kidney damage and severe skin lesions

This paper was published in the Annals of Saudi Medicine 2012 May-Jun;32(3):309-11

 

Study title and authors:

A fatal case of cutaneous adverse drug-induced toxic epidermal necrolysis associated with severe rhabdomyolysis.

Noordally SO, Sohawon S, Vanderhulst J, Duttmann R, Corazza F, Devriendt J.

Department of Critical Care Medicine, Centre Hospitalier Universitaire de Tubize-Nivelles, 1400 Nivelles, Belgium. Sheikoaleed.Noordally@chu-brugmann.be

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22588445

 
Toxic epidermal necrolysis is a life-threatening skin condition that is usually induced by a reaction to medications. Atorvastatin is a recognized cause of rhabdomyolysis (the breakdown of muscle fibers that leads to kidney damage). Naproxen is a widely used nonsteroidal anti-inflammatory (NSAID) drug that is a known cause of skin lesions.
 
This paper reports of a fatal case of drug-induced toxic epidermal necrolysis associated with severe muscle necrosis (death of muscle cells) due to the use of Naproxen and a statin.
 
(i) A 61-year-old female patient was admitted to hospital with complaints of breathing difficulties, vomiting, and diarrhea that started two days prior to admission.
(ii) Her medications included atorvastatin 10 mg once daily and naxproxen 500 mg three times a day. 
(iii) Acute kidney injury and rhabdomyolysis were present on admission to the hospital.
(iv) She had very high levels of creatine phosphokinase (indicating muscle damage by statins).
(v) Naproxen treatment had started ten days before admission and had led to the rapid onset of skin lesions.
(vi) The patient rapidly developed multiple organ failure with respiratory failure, and complete skin necrosis (death of skin tissue). Despite treatment she died the following day.

The paper concludes that the patient died of drug induced toxic epidermal necrolysis associated with severe muscle necrosis due to the use of naproxen and statin drugs leading to acute kidney damage and complete skin necrosis.

Rhabdomyolysis induced by statins

This paper was published in Clinical Chemistry 1990 Dec;36(12):2145-7

Study title and authors:
Rhabdomyolysis secondary to lovastatin therapy.

Manoukian AA, Bhagavan NV, Hayashi T, Nestor TA, Rios C, Scottolini AG.
Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu 96822.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/2253372

This paper reports a case of lovastatin (Mevacor)-induced rhabdomyolysis (severe muscle breakdown which may lead to kidney damage).

(i) A 59 year old woman was admitted to hospital with a two day history of shortness of breath and difficulty walking. She had been discharged from hospital two weeks earlier for congestive heart failure and, since discharge, had experienced progressive weight gain and swelling of the feet and ankles such that walking had become difficult.
(ii) For 13 days before admission to hospital she had been taking lovastatin, 20 mg orally twice a day.
(iii) On the second hospital day she complained of profound muscle weakness in her lower extremities which progressed over several hours to include the upper extremities. In addition she could no longer walk because of severe pain.
(iv) Creatine kinase levels increased from 157 U/L two weeks before admission to 176,500 U/L on the twelfth hospital day. (High creatine kinase levels are a marker for rhabdomyolysis).
(v) The patient's symptoms and creatine kinase levels resolved after discontinuation of the statin drug.

As well as inhibiting the body from producing cholesterol, statins also repress the production of several other biologically essential compounds such as coenzyme Q10 and heme A which are important components in the system of mitochondrial energy production.

Mitochondria are known as the powerhouses of the cell. They are tiny cellular organelles that take in nutrients, break them down, and create energy for the cells.

Dr Manoukian speculates that the rhabdomyolysis was due to statin-induced mitochondrial damage secondary to inadequate synthesis of coenzyme Q10 and heme A.

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.

Even brief exposure to statins causes muscle damage

This post includes a synopsis of a study published in the Archives of Neurology 2004 Jun;61(6):889-92

Study title and authors:
Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke.
Rundek T, Naini A, Sacco R, Coates K, DiMauro S.
Department of Neurology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/15210526

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Rundek notes there have been various adverse effects of statin drugs, including problems commonly affecting muscle and ranging from muscle pain to the rapid destruction of skeletal muscle which can then cause kidney failure (rhabdomyolysis). These adverse effects may be due to a coenzyme Q(10) (CoQ(10)) deficiency because inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ(10).

The objective of the study was to measure CoQ(10) levels in blood from subjects with high cholesterol levels before and after exposure to atorvastatin at 14 and 30 days.

 
The study found:
(a) Coenzyme Q(10) levels dropped by 51% after 30 days of statin thearpy.
(b) A significant decrease was already detectable after 14 days of treatment.
 
To conclude: Even brief exposure to statins causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, muscle pain, and rhabdomyolysis.

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Rhabdomyolysis induced by a single dose of a statin.

This post includes a summary of a study published in Heart 2004 Jan;90(1):e3

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Study title and authors:

Rhabdomyolysis induced by a single dose of a statin.

Jamil S, Iqbal P.

Medical Directorate, Chesterfield and North Derbyshire Royal Hospital NHS Calow, Chesterfield, UK.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/14676266?dopt=Abstract

Statins have been shown to cause toxic effects on muscles and rhabdomyolysis. In most cases rhabdomyolysis occurs following the use of these drugs for at least one week.

This paper reports a case of rhabdomyolysis after just a single dose of simvastatin.

(i) A 54 year old man was admitted to hospital with a one week history of shortness of breath and was found to have high blood pressure. 

(ii) He was treated with various drugs including simvastatin (40 mg/day).
(iii) After one dose of simvastatin he was found to have a raised creatinine kinase concentration of 11,290 μ/l (normal 10-120 μ/l) with a raised urine myoglobin concentration of 46,560 μg/ml (normal 0–50 μg/ml). (Raised levels of creatinine kinase and urine myoglobin are associated with rhabdomyolysis).
(iv) All his parameters improved when simvastatin treatment was stopped.

This case highlights that rhabdomyolysis may be caused by a reaction to simvastatin.

The reasearchers conclude: "Clinicians should be aware of this possible complication presenting in the early days of the use of statins".

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Statins And Cancer: Cause For Concern

This post featues a paper published in the British Medical Journal 17 November 2001;323:1145

Study title and authors:
Statins And Cancer: Cause For Concern
Uffe Ravnskov, Paul J. Rosch, Peter H.Langsjoen, Joel M. Kauffman, and Kilmer S. McCully
Magle Stora Kyrkogata 9, S-22350 Lund, Sweden.
This paper can be accessed at: http://www.bmj.com/cgi/eletters/323/7322/1145#26439
 
Dr Uffe Ravnskov has published over 80 scientific papers regarding the cholesterol, saturated fat, heart disease hypothesis. Here he questions the wisdom of recommending statin treatment for a large segment of the world’s population simply because they have elevated cholesterol levels or are assumed to be at increased risk for coronary events because of the presence of other risk markers.

He finds:
(i) It is already known that statins may induce fatal rhabdomyolysis, cardiac insufficiency, peripheral polyneuropathy, hepatic toxicity, and mental disturbances.
(ii) A much more momentous issue is that all statins have proven carcinogenic.
(iii) In the Heart Protection Study non-melanoma skin cancer was seen in 243 patients treated with simvastatin compared with 202 cases in the control group. 
(iv) In the Scandinavian Simvastatin Survival Study non-melanoma skin cancer was seen in 13 patients treated with simvastatin compared with six in the control group.
(v) Also disquieting was the significant increase in breast cancer rates in patients treated with pravastatin in the Cholesterol and Recurrent Events trial.

Statin drug induces rhabdomyolysis

This post includes a summary of a paper published in Clinical Therapeutics 2007 Jan;29(1):172-6

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Study title and authors:

Asymptomatic statin-induced rhabdomyolysis after long-term therapy with the hydrophilic drug pravastatin.

Schindler C, Thorns M, Matschke K, Tugtekin SM, Kirch W.

Institute of Clinical Pharmacology, Faculty of Medicine, Technical University of Dresden, Dresden, Germany. christoph.schindler@tu-dresden.de

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17379057

This paper discusses how a patient developed rhabdomyolysis after three years of statin treatment.

(i) A male patient aged 73 years presented to the emergency department with dyspnea (shortness of breath).
(ii) He had undergone heart transplantation seven years earlier and been receiving daily pravastatin therapy for more than three years without complaining of any symptoms.
(iii) Laboratory testing revealed that his creatine kinase levels was substantially above the reference range. (High creatine kinase levels indicate injury or stress to muscle tissue, the heart, or the brain).
(iv) Pravastatin was immediately discontinued, and the patient was admitted to the intensive care unit for treatment.
(v) Creatine kinase values declined after three days, and they returned to within reference range after three weeks.
(vi) The patient was diagnosed with acute rhabdomyolysis.

Schindler concludes: "The occurrence of acute statin-induced rhabdomyolysis in this case suggests that statins may have the potential to damage myocytes (muscle cells)".
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