Statin safety: a systematic review

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Am J Cardiol. 2006 Apr 17;97(8A):S52-60.

Statin safety: a systematic review.

Law M, Rudnicka AR.

Wolfson Institute of Preventive Medicine, Barts and The London School

of Medicine, London, United Kingdom.

A systematic review of cohort studies, randomized trials, voluntary

notifications to national regulatory authorities, and published case

reports was undertaken to assess the incidence and characteristics of

adverse effects in patients treated with 3-hydroxy-3-methylglutaryl

coenzyme A (HMG-CoA) reductase inhibitors, or statins. For statins

other than cerivastatin, the incidence of rhabdomyolysis in 2 cohort

studies was 3.4 (1.6 to 6.5) per 100,000 person-years, an estimate

supported by data from 20 randomized controlled trials. Case fatality

was 10%. Incidence was about 10 times greater when gemfibrozil was

used in combination with statins. Incidence was higher (4.2 per

100,000 person-years) with lovastatin, simvastatin, or atorvastatin

(which are oxidized by cytochrome P450 3A4 [CYP3A4], which is

inhibited by many drugs) than pravastatin or fluvastatin (which are

not oxidized by CYP3A4). In persons taking simvastatin, lovastatin,

or atorvastatin, 60% of cases involved drugs known to inhibit CYP3A4

(especially erythromycin and azole antifungals), and 19% involved

fibrates, principally gemfibrozil. The incidence of myopathy in

patients treated with statins, estimated from cohort studies

supported by randomized trials, was 11 per 100,000 person-years. For

liver disease, randomized trials reported fewer hepatobiliary

disorders in patients allocated statins than in those allocated

placebo. The notification rate of liver failure to regulatory

authorities was about 1 per million person-years of statin use.

Randomized trials show no excess of renal disease or proteinuria in

statin-allocated participants, and the decline in glomerular

filtration rate was smaller with statins than with placebo.

Evidence from 4 cohort studies and case reports suggests that statins

cause peripheral neuropathy, but the attributable risk is small (12

per 100,000 person-years). No change in cognitive function was found

in randomized trials of statins in elderly patients.