100 QUESTIONS IN CARDIOLOGY

12 What are the side effects of lipid-lowering

therapy, and how should they be monitored?

John Betteridge

Statins

These are generally well tolerated. In the major end point trials,

adverse events were little different from placebo.

• Myositis, defined as painful, tender muscles with a high CPK, is

rare, occurring with a frequency of lower than 1 in 10,000

patient years. Routine CPK measurement is not recommended

as modest elevations (generally secondary to physical activity)

are quite common even in patients on placebo treatment. It is

important to remember that black patients have higher CPKs

than whites, and that hypothyroidism is an important cause of

raised CPK. Patients should be warned to stop the drugs if

severe muscle pain is experienced.

• Liver functionshould be checked prior to statin therapy as

abnormal hepatic function and high alcohol intake are relative

contraindications for these drugs which are metabolised

principally through the liver. Approximately one in 400 patients

will develop greater than 3-fold transaminase increases which

revert to normal with dose reduction or stopping of the drug. They

can be used in moderate renal impairment. It is good practice to

check liver function tests periodically during statin therapy.

Fibrates

These are also generally well tolerated but can also cause myositis

and hepatic dysfunction. Clofibrate (in the WHO trial) was

associated with increased gallstone formation through increased

biliary cholesterol content. This drug is now redundant and the

newer fibrates have less impact on biliary composition. Doubt

remains concerning long term safety with the fibrate class in

terms of non-cardiac mortality. However the WHO clofibrate trial

was the major contributor to this concern. The recent VA HIT

study (reported at the AHA meeting in Dallas, November 1998)

showed that gemfibrozil reduced risk by approximately a quarter