Short summary

The evidence regarding a putative association between statin use and risk of polyneuropathy is conflicting. The purpose of this cohort study is to prospectively investigate the effect of statin use on the peripheral nerve system. We will collect data at baseline and at 1-year follow-up, and compare changes in symptoms, signs and extensive paraclinical tests among patients using the drug, compared with individuals not exposed to statins.

Rationale

Statins are cholesterol-lowering drugs. The use of statins has increased markedly from 1% of the Danish population in 1999 to 11% in 2015. Given the widespread use of statins, it is crucial to investigate potential side effects of this class of drugs. Polyneuropathy is a disorder of the peripheral nerves, which causes considerable morbidity in terms of sensory or motor symptoms, and is frequently painful.

To date, a number of studies examining a possible link between statin use and polyneuropathy have produced equivocal results. One possible limitation is the lack of detailed follow-up data in most studies performed so far. We therefore designed the present study, where detailed clinical, neurophysiological and skin biopsy information is collected in a standardized fashion for patients on statins and a comparison group of individuals not exposed to statins.

Description of the cohort

Exposed cohort:

We will recruit 66 participants among patients admitted to the Department of Neurology, Odense University Hospital, Denmark, or seen in the outpatient clinic of the department with cerebral infarction or transient ischemic attack (TIA). Participants are aged 40-80 years, with no previous use of cholesterol-lowering medicine, including statins, and with no co-morbidities that can cause neuropathy. Participants are considered eligible for the study, if the physician in charge of their admission plans to initiate treatment with simvastatin 40 mg daily.

Unexposed cohort:

We will recruit 50 participants via advertisements in the local community and on the internet (www.sundhed.dk) and by asking the spouse of the exposed participants. Inclusion and exclusion criteria are mainly the same as mentioned above, except that participants in this group do not take any statins.

Data and biological material

In order to examine the possible changes of the nerves we will test the following at baseline and after 1 year:

• Nerve conduction study
• Skin biopsies (to count the number of nerve endings)
• Sensory testing
• Neurological rating scales

In addition we will take blood samples for analyses (e.g., HbA1c, cholesterol levels) and for storage in a biobank. Information about statin use will be retrieved from a local prescription registry (Odense Pharmacoepidemiologic Prescription Database).

Participants in the unexposed group will additionally be tested 6 weeks after baseline to test for variation in repeated Measurements.

Collaborating researchers and departments

Department of Neurology, Odense University Hospital, Denmark and Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark

• PhD-student Toke de Koning Svendsen, MD

• Professor and Consultant Søren H. Sindrup, DrMSc

• Professor and Consultant David Gaist, PhD

• PhD student, Thomas Krøigård, MD

• Consultant Søren Bak, PhD

Department of Pathology, Odense University Hospital

• Professor and Consultant Henrik Daa Schrøder, DrMSc

• Martin Wirenfeldt Nielsen, MD, PhD

Clinical Pharmacology, Odense University Hospital and Institute of Public Health, University of Southern Denmark

• Jesper Hallas, MD, DrMSc