Both clinicians and patients were surprised by the withdrawal of cerivastatin from the US market in 2001 because of reports of serious myopathy, including severe rhabdomyolysis.
Both clinicians and patients were surprised by the withdrawal of cerivastatin from the US market in 2001 because of reports of serious myopathy, including severe rhabdomyolysis. As a class, the HMG-CoA reductase inhibitors (statins) are generally well tolerated and have an excellent safety profile.
Statins do pose a small but definite risk of myopathy when used alone; the risk is higher when they are given with a fibrate. Lovastatin and simvastatin are associated with a 0.08% incidence of severe myopathy,1,2 and the other currently available statins appear to carry a similar risk.
A recent clinical advisory from the American College of Cardiology, American Heart Association, and National Heart, Lung, and Blood Institute provides recommendations on the appropriate use of statins, including precautions, contraindications, and tips for safety monitoring.3 Highlights follow.
Order baseline liver function tests and obtain a lipid and lipoprotein profile before statin therapy is started. Modest elevations in transaminase levels (less than 3 times the upper limit of the normal range) are not a contraindication to statin therapy, as long as the patient is carefully monitored.
A baseline creatine kinase (CK) measurement is also recommended because CK elevations are common and pretreatment levels are valuable to have for comparison. Advise patients who take statins to report any muscle discomfort or weakness or brown urine immediately; these findings mandate CK measurement.
MONITORING FOR ADVERSE REACTIONS
Patients with muscle symptoms. Symptoms of myositis can appear at any time after statin therapy is initiated and are cause for discontinuing treatment. Keep the following points in mind when you monitor patients:
Patients without muscle symptoms. Before cerivastatin was withdrawn from the market, routine monitoring of CK in asymptomatic patients was not recommended. If you elect to monitor CK values in asymptomatic patients, keep these recommendations in mind:
PREVENTING ADVERSE REACTIONS
Most cases of statin-associated myopathy occur in patients with risk factors, such as advanced age, small body size, multisystem disease, and use of concomitant or multiple medications. The risk of myopathy is also increased during the perioperative period (Table).
Other caveats include:
REFERENCES:1. Cressman MD, Hoogwerf BJ, Moodie DS, et al. HMG-CoA reductase inhibitors. A new approach to the management of hypercholesterolemia. Cleve Clin J Med. 1988;55:93-100.
2. Hunninghake DB. Drug treatment of dyslipoproteinemia. Endocrinol Metab Clin North Am. 1990;19: 345-360.
3. Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Circulation. 2002;106:1024-1028.