Re: re: statins causing neuropathy?

[Guest guest]

Is it possible that neuropathy seen in patients on statins is related to diabetes???

Peripheral neuropathy and lipid-lowering therapy.

South Med J. 1998 Jul;91(7):667-8.

Ziajka PE, Wehmeier T.

Florida Lipid Associates, Orlando 32806, USA.

We report a case of a peripheral neuropathy induced and exacerbated by several commonly used HMG-CoA reductase inhibitors including lovastatin, simvastatin, pravastatin, and atorvastatin, and the vitamin niacin. A review of the literature shows similar cases with individual lipid-lowering drugs, but this case shows the cross-reactivity of the neuropathic process to different HMG-CoA reductase inhibitors, and it is the first reported case of a peripheral neuropathy exacerbated by the use of niacin.

Statin Drugs May Increase Risk Of Peripheral Neuropathy

St. , MN - Statin drugs can increase the risk of developing peripheral neuropathy, according to a study published in the May 14 issue of Neurology, the scientific journal of the American Academy of Neurology (2002).

Peripheral neuropathy results from damage to the peripheral nerves and causes weakness, numbness and pain in the hands and feet. Statin drugs are prescribed for millions of Americans to lower cholesterol.

People taking statins were 14 times more likely to develop peripheral neuropathy than people who were not taking statins, according to the Danish study. However, the overall risk of developing neuropathy is rare, said study author Gaist, MD, PhD, of the University of Southern Denmark in Odense.

"The positive benefits of statins, particularly on reducing the risk of heart disease, far outweigh the potential risk of developing neuropathy," Gaist said. "These findings shouldn't affect doctor or patient decisions to start using statins. But if people who take statins develop neuropathy symptoms, they should talk with their doctor, who may reconsider the use of statins."

For the population-based study, the researchers used a patient registry to identify all of the first-time cases of peripheral neuropathy with no known cause (such as diabetes) in Funen County, Denmark, over a five-year period. Each case was matched to 25 people of the same age and sex with no neuropathy as a control group. The use of statins was then determined for each group.

They identified 166 cases of first-time neuropathy with no known cause. Of those, 35 had a definite diagnosis, 54 were probable cases and 77 were possible cases. Nine of the people with neuropathy had taken statins. They had taken statins for an average of 2.8 years.

For those with a definite diagnosis of neuropathy, the statin users' risk of developing neuropathy was 16 times higher than for the control group. When all cases of neuropathy were taken into account, the statin users' risk of developing neuropathy was four times higher than the control group's risk.Taking statins for longer periods of time and taking higher doses of them increased the risk of developing neuropathy.

Statins lower levels of low-density lipoprotein (LDL) cholesterol by blocking the production of a liver enzyme used by the body to make cholesterol.

The American Academy of Neurology, an association of more than 17,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. For more information about the American Academy of Neurology, visit its web site at http://www.aan.com.

Statins and risk of polyneuropathy

A case-control study

Neurology 2002;58:1333-1337

D. Gaist, MD PhD, U. Jeppesen, MD PhD, M. Andersen, MD PhD, L. A. García Rodríguez, MD MSc, J. Hallas, MD PhD and S. H. Sindrup, MD PhD

From the Department of Neurology (Drs. Gaist, Jeppesen, and Sindrup), Odense University Hospital; Epidemiology (Dr. Gaist) and Clinical Pharmacology (Drs. Andersen, Hallas, and Sindrup), Institute of Public Health, University of Southern Denmark; and Centro Español de Investigación Farmacoepidemiológica (Dr. García Rodríguez), Madrid, Spain.

Address correspondence and reprint requests to Dr. Gaist, Epidemiology, Institute of Public Health, University of Southern Denmark, Sdr Boulevard 23A, 5000 Odense C, Denmark; e-mail: dgaist@... or dg@...

Background: Several case reports and a single epidemiologic study indicate that use of statins occasionally may have a deleterious effect on the peripheral nervous system. The authors therefore performed a population-based study to estimate the relative risk of idiopathic polyneuropathy in users of statins.

Method: The authors used a population-based patient registry to identify first-time-ever cases of idiopathic polyneuropathy registered in the 5-year period 1994 to 1998. For each case, validated according to predefined criteria, 25 control subjects were randomly selected among subjects from the background population matched for age, sex, and calendar time. The authors used a prescription register to assess exposure to drugs and estimated the odds ratio of use of statins (ever and current use) in cases of idiopathic polyneuropathy compared with control subjects.

Results: The authors verified a diagnosis of idiopathic polyneuropathy in 166 cases. The cases were classified as definite (35), probable (54), or possible (77). The odds ratio linking idiopathic polyneuropathy with statin use was 3.7 (95% CI 1.8 to 7.6) for all cases and 14.2 (5.3 to 38.0) for definite cases. The corresponding odds ratios in current users were 4.6 (2.1 to 10.0) for all cases and 16.1 (5.7 to 45.4) for definite cases. For patients treated with statins for 2 or more years the odds ratio of definite idiopathic polyneuropathy was 26.4 (7.8 to 45.4).

Conclusions: Long-term exposure to statins may substantially increase the risk of polyneuropathy.

HMG-CoA-reductase inhibitors and neuropathy

Introduction

HMG-CoA reductase inhibitors (statins) lower both the total cholesterol level and the LDL- cholesterol level. The HMG-CoA -reductase inhibitors are competitive inhibitors of the enzyme 3-

hydroxy-3-methylglutargyl coenzyme A reductase, an enzyme that is of major importance in the synthesis of cholesterol. As a group the HMG-CoA reductase inhibitors are, combined with dietary measures, indicated for hypercholesterolemia. They are effective in both the primary and secondary prevention of coronary diseaseand stroke prevention [1].

Gastrointestinal complaints are the most frequently reported adverse reactions of HMG-CoA-reductase inhibitors. Elevation of the liver-enzymes (up to more than three times the upper normal level) and myopathy, including myositis and rhabdomyolysis, are the two most severe adverse drug reactions of the HMG-CoA- reductase inhibitors [2-6]. Patient deaths due to rhabdomyolysis resulted in the withdrawal of cerivastatin.

Peripheral neuropathy is a general term which includes a variety of conditions characterised by paraesthesias, sensory loss, muscle weakness, and hyperaesthesias of the extremities. The back-ground incidence (age- and sex-adjusted) for peripheral neuropathy not associated with alcohol or diabetes is 1.5 cases per 10,000 person-years (95% CI 0.9 - 2.3). The back-ground

incidence (age and sex-adjusted) for diabetic polyneuropathy is 5.4 cases per 10,000 person-years (95% CI 3.3 - 8.3) [7].

Peripheral neuropathy is mentioned in the SPC of atorvastatin (Lipitor®) as an uncommonly (0.1-1%) occurring adverse reaction [5]. The SPC of simvastatin (Zocor®) mentiones peripheral neuropathy as an adverse reaction, which occurred in non-controlled trials and post-marketing surveillance [2]. SPC's of the other HMG-CoA-reductase inhibitors do not mention (peripheral) neuropathy as a possible adverse drug reaction.

Reports

On March 8 2004 the database of the Netherlands Pharmacovigilance Centre Lareb contained ten reports of neuropathy, expressed as neuropathy, peripheral neuropathy or polyneuropathy, in association with the use of HMG-CoA-reductase inhibitors. In addition to these reports the database contained 26 reports of paraesthesias, one report of sensory loss, 22 reports of muscle weakness and no reports of hyperaesthesias, conditions that might be a symptom of neuropathy. From the ten reports of neuropathy, five concerned simvastatin, three pravastatin and two atorvastatin. In four cases the suspect HMG-CoA-reductase inhibitor has been discontinued and in these cases the patient (partially) recovered. The mean time to onset is 25.5 months (range

0.75 to 72 months).

Table 1 shows an overview of all reports concerning neuropathy, peripheral neuropathy and polyneuropathy associated with the use of HMG-CoA-reductase inhibitors.

Other sources of information

Literature

According to Backes and [8], two epidemiologic studies and several case reports (with a total of 15 patients) have demonstrated a possible increased risk of peripheral neuropathy in patients using HMG-CoA-reductase inhibitors [8].

s [9] described a case of peripheral neuropathy in a patient treated with lovastatin and pravastatin. A 47-year-old woman with hypercholesterolemia experienced sensory neuropathy within two years after starting with lovastatin 20 mg daily. After discontinuation of lovastatin she recovered within eight weeks. After starting with pravastatin 20 mg daily she developed within two weeks progressive paraesthesias of the extremities, which diminished within four weeks after discontinuation of pravastatin [9]