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HMG-CoA Reductase Inhibitor Therapy and Peripheral Neuropathy
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TO THE EDITOR:
Lovastatin and pravastatin are inhibitors of the rate-limiting agent in cholesterol synthesis, 3-hydroxy-3 methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Effective in lowering both low-density lipoprotein and total cholesterol levels, they are generally well tolerated. Documented adverse effects include gastrointestinal disturbances, rash, headaches, myalgias, myopathy, and increases in aminotransferase values [1, 2].
I report a case of reversible sensory neuropathy associated with lovastatin and pravastatin therapy. A 47-year-old woman was seen for a routine check-up in May 1991. Except for mild obesity, her complete examination was normal, including intact ankle reflexes and vibratory sensation. Laboratory findings showed normal values for renal and liver function, blood sugar, and erythrocyte and leukocyte counts. Two fasting lipid analyses obtained 2 months apart confirmed a diagnosis of type IIa hypercholesterolemia (total cholesterol levels, 275 and 270 mg/dL; high-density lipoprotein cholesterol levels, 58 and 59 mg/dL; low-density lipoprotein [LDL] cholesterol levels, 190 and 178 mg/dL; triglycerides, normal). In June 1991, she began receiving lovastatin, 20 mg each evening. In July 1992, her total cholesterol level was 235 mg/dL, and her LDL cholesterol level was 124 mg/dL. When next seen in June 1993, she reported stocking and glove paresthesias that were initially intermittent but eventually became constant. Results of a repeat chemistry panel, complete blood count, and sedimentation rate were normal. Lovastatin was stopped, and the symptoms abated over the next 8 weeks. In August 1993, pravastatin was started at a dose of 20 mg daily. Within 2 weeks, paresthesias returned and progressed to involve her upper extremities to the elbows and her lower extremities to the knees. No other neurologic or systemic symptoms were evident. She was taking no other medications. Physical examination showed intact deep tendon reflexes but slightly diminished vibratory sensation at the ankles and wrists. Pravastatin was stopped, and her paresthesias regressed over the next 4 weeks.
Because cholesterol is a ubiquitous component of human cell membranes, interference with its synthesis may have many consequences. The 1993 Physicians' Desk Reference lists “paresthesias” and “peripheral neuropathy” as possibly related to lovastatin and pravastatin therapy but at a frequency that did not differ statistically from that associated with placebo. This side effect is not listed in a recent review of cholesterol-lowering drugs [1]. A MEDLINE database search from 1980 to 1993 also uncovered no such cases. In the lovastatin 5-year safety and efficacy study [2], 745 patients were treated with lovastatin for a median of 5.2 years. One instance of peripheral neuropathy was noted but not described, and its cause was uncertain.
The appearance, disappearance, and reappearance of symptoms in association with treatment and retreatment with related cholesterol-lowering medications strongly suggest that a peripheral sensory neuropathy may occur with the HMG-CoA reductase inhibitors.
Michael B. Jacobs, MD
Stanford University Clinic; Palo Alto, CA 94304-2205
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
