Simvastatin Dose And Risk Of Rhabdomyolysis: Nested Case-Control Study Based On New Zealand National Health and Drug Dispensing Data
Statins are one of the most widely prescribed classes of drugs, therefore reliable estimates of adverse effects are important. Two randomised controlled trials have found higher rates of rhabdomyolysis in users of 80mg versus 20mg simvastatin, but there is limited information about the risk associated with other doses. Clinical guidelines in some countries specifically recommend simvastatin as the first-line statin for the primary and secondary prevention of cardiovascular events, hence further investigation into dose-related risk is warranted. We undertook a nested case-control study, using routinely collected national health and drug dispensing data, to estimate the relative and absolute risks of rhabdomyolysis resulting in hospital admission or death according to simvastatin dose.
METHODS:
The underlying study cohort comprised all patients (n=313,552) who initiated a new episode of simvastatin use in New Zealand between 1 May 2005 and 31 December 2009. Cases (n=29) were patients with a diagnosis of rhabdomyolysis after cohort entry, confirmed by hospital discharge letter or death records. Ten controls, matched by year of birth and sex, were randomly selected from the study cohort using risk set sampling. Odd ratios and 95% CIs were estimated using conditional logistic regression.
RESULTS:
Current users of 40mg simvastatin daily were five times as likely to develop rhabdomyolysis as those taking 20mg (adjusted odds ratio 5.3 [95% CI 1.9–15.0]). The absolute excess risk of rhabdomyolysis associated with the use of 40mg versus 20mg was about 10 per 100,000 person-years; the incidence rates were 11.5 (95% CI 7.1–17.5) and 2.1 (95% CI 0.7–4.8) per 100,000 person-years respectively.
CONCLUSIONS:
These findings provide reassurance that the absolute risk of rhabdomyolysis in a general population of simvastatin users is very low. Nonetheless, they also raise questions about the optimal simvastatin regimen to maximise cardiovascular benefits and minimise the risk of serious muscle injury.