Clinical Perspectives of Statin-Induced Rhabdomyolysis

Antons, Kenneth; Williams, Craig D.; Baker, Steven K.; Phillips, Paul S

doi:10.1016/j.amjmed.2006.02.007

Cited by 206 publications

(125 citation statements)

References 95 publications

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“…Advanced age, renal and hepatic failure, thyroid dysfunction, hypertriglyceridemia, exercise, Asian race and perioperative period are accepted risk factors 8 . Despite the fact of CLAM has been described as a necrotizing myopathy 9 , some authors have noted relative absence of muscle fiber degeneration, even in patients with marked weakness and elevated CPK 7 .…”

Section: Discussionmentioning

confidence: 99%

Myotonic potentials in statin-induced rhabdomyolysis

Almeida

Lissa

Melo

2008

Arq. Neuro-Psiquiatr.

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Lipid lowering drugs are used worldwide to control dyslipidemias. The muscle disorder associated with them are coined cholesterol-lowering agents myopathy (CLAM) 1 . The annual incidence of rhabdomyolysis in patients taking statins is 3.4 per 100000 persons 2 . Between 1987 and 2001 there were 42 deaths +related to statin-induced rhabdomyolysis, resulting in a mortality rate of 0.15 per million of prescriptions 3 . Although myotonic potentials have been described in some drug-related myopathies, they are rarely reported in CLAM. Though there are a few experimental myotonic myopathy associated with statin in rabbits 4-6 , there was only one single report describing 5 patients with this finding in humans 7 .We report a patient with statin-related rhabdomyolysis and profuse myotonic potentials in the needle EMG with clinical and electrophysiological recovery shortly after the statin interruption. CaSeA 68 year-old Asian Brazilian woman was admitted with progressive painless weakness for one week, started on the proximal muscles of the four limbs and neck flexors with rapid progression to inability to walk and elevate the limbs. Urine was redbrown in color. Thirty days before the admission she was put on simvastatin due to hypercholesterolemia. Other medication she was taking was enalapril for mild hypertension. There was no personal or family history of myopathy. On neurological examination, abnormal findings were grade 2 (MRC) strength in the proximal lower limb muscles and grade 3 in the proximal upper limb muscles, grade 4 in the distal muscles and hypoactive deep tendon reflexes. No clinical myotonia was detected.A complete blood count, electrolytes, creatinine, glucose, TSH, and free T4 were all normals. Myoglobin was detected in the urine. CPK was 22.260 U/l on the admission day and 55.000 U/l on the third day. AST and ALT were 790 and 750 U/l, respectively. The nerve conduction studies perfomed in both arms and legs showed normal results in the median, ulnar, superficial radial, tibial, peroneal, superficial peroneal and sural nerves bilaterally. The F wave latencies were normal in the median, ulnar, fibular and tibial nerves bilaterally. The needle EMG perfomed with disposable monopolar needle in cervical paraspinal, supraspinatus, deltoid, triceps, abdutor pollicis brevis and first dorsal interosseus in the upper right limb and tibialis anterior, gastrocnemius, vastus lateralis and iliopsoas in the right lower limb showed rare positive sharp waves and fibrillations in the right supraspinatus muscle, as well as a few small amplitude and short duration (SASD) motor unit potentials (MUP) in the right iliopsoas muscle. On the other hand, the needle study showed profuse amount of myotonic potentials in deltoid, supraspinatus, iliopsoas and cervical paraspinal muscles on the right side (Fig 1).Simvastatin was stopped and vigorous hydration was started to prevent acute renal failure. She was discharged two weeks later with normal strength, renal function and CPK levels. A second needle EMG performed 30 days after...

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Section: Discussionmentioning

confidence: 99%

Myotonic potentials in statin-induced rhabdomyolysis

Almeida

Lissa

Melo

2008

Arq. Neuro-Psiquiatr.

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“…In hypothyroid patients, myopathy with mild elevation of serum CK activity is not rare and in a few cases might take the form of overt rhabdomyolysis even in patients not on statin treatment. However, if statin treatment is added it seems that the risk of muscle-related side effects increases markedly [91][92][93][94][95][96][97]. It is therefore recommended that a clinical examination, thyroid-stimulating hormone (TSH) and thyroxine levels measurement should be performed before statin treatment initiation.…”

Section: Thyroid Diseases and Statin Intolerancementioning

confidence: 99%

“…Given that patients with hypothyroidism have been excluded from statin clinical trials there are limited data regarding the incidence of statin muscle toxicity in patients with hypothyroidism [92][93][94][95][96][97]. In hypothyroid patients, myopathy with mild elevation of serum CK activity is not rare and in a few cases might take the form of overt rhabdomyolysis even in patients not on statin treatment.…”

Section: Thyroid Diseases and Statin Intolerancementioning

confidence: 99%

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Banach

Rizzo²,

Tóth

et al. 2015

Expert Opinion on Drug Safety

181

204

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“…Simvastatin has been shown to increasing cytosolic calcium by direct diffusion through sarcolemma and impairing membrane integrity due to prenylated protein deficiency which is a class effect. In addition, it induced altered mitochondrial function and thereby mitochondrial calcium efflux through the Na + /Ca 2+ exchanger or permeability transient pore which leads to large calcium release from sarcoplasmic reticulum (13,14). This along with defective oxidative metabolism in the setting of rhabdomyolysis leads to Ca+2 ATPase pump dysfunction due to ATP depletion.…”

Section: O N I I N T E R N a Z I O N A L Imentioning

confidence: 99%

“…Deficiencies of synthetic products of the HMG (3-hydroxy-3-methylglutaryl) CoA reductase pathway have been implicated as possible mechanisms. Abnormal membrane integrity secondary to cholesterol deficiency, abnormal mitochondrial respiratory function secondary to coenzyme Q 10 deficiency and abnormality in cell signaling cascades involving Rho, Ras and Rap-1a, apoptosis secondary to prenylated protein deficiency are the proposed mechanisms (13,14). Simvastatin has been shown to increasing cytosolic calcium by direct diffusion through sarcolemma and impairing membrane integrity due to prenylated protein deficiency which is a class effect.…”

Section: O N I I N T E R N a Z I O N A L Imentioning

confidence: 99%

Bone scintigraphy of severe hypercalcemia following simvastatin induced rhabdomyolysis

Mirza

Amorosa

2016

ccmbm

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SummarySimvastatin induced rhabdomyolysis with renal failure is a well reported clinical entity with hyperkalemia recognized as a life threatening risk. The risk of delayed hypercalcemia during the recovery of renal function is not well appreciated as this varies in severity and can be caused by multiple mechanisms. We present a patient with high dose simvastatin induced rhabdomyolysis leading to late onset of severe hypercalcemia due to calcium phosphate deposition in muscles diagnosed by distinctive bone scintigraphy. A 60-year-old Asian male was admitted to the hospital for profound weakness one week following the initiation of simvastatin 80 mg daily post myocardial infarction. His clinical course was complicated by contrast nephropathy. One week later, he developed progressive weakness in all his extremities and inability to raise his head and eat. Simvastatin was discontinued at this point. CPK elevation to greater than 425,000 U was found, consistent with rhabdomyolysis. He became oliguric requiring hemodialysis. Muscle biopsy showed severe muscle necrosis and type 2 fiber atrophy. One month later, he developed hypercalcemia with suppressed intact PTH and 1, 25(OH) D levels. Whole body bone scintigraphy showed calcium phosphate deposition throughout his musculature. His calcium levels normalized in 1 week on hemodialysis. This patient's experience illustrates the marked risk of delayed severe hypercalcemia from rhabdomyolysis due to dissolution of myocellular calcium phosphate deposits. It also provides an opportunity to review the different mechanisms of hypercalcemia especially in statin induced rhabdomyolysis. Recognition of this phenomenon is critical for appropriate follow up and treatment of such patients.

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Clinical Perspectives of Statin-Induced Rhabdomyolysis

Cited by 206 publications

References 95 publications

Myotonic potentials in statin-induced rhabdomyolysis

Myotonic potentials in statin-induced rhabdomyolysis

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Bone scintigraphy of severe hypercalcemia following simvastatin induced rhabdomyolysis

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