What are the current guidelines for monitoring adverse effects in patients treated with statins?
Ian Graham: The current European guidelines look particularly at when to measure liver enzymes, when to measure muscle enzymes, and how to handle muscle pain.
With regard to liver enzymes, if the alanine transaminase (ALT) is less than 3 times the upper limit of normal, the guideline suggests that treatment with statins can be continued, but the test should be repeated in 4 to 6 weeks. If the ALT is above 3 times normal, the statins should be reduced or stopped, and the test repeated in 4 to 6 weeks. Then the statin can be resumed in a lower dose or a different statin [can be introduced] if the result has returned to normal. It is recommended that liver enzymes should be checked before treatment and once 8 to 12 weeks after starting treatment, and if normal, it is not necessary to continue to measure liver enzymes after that.
With regard to muscle enzymes, that is creatine kinase (CK), these should be measured before starting statin treatment. If the baseline is less than 4 times the upper limit of normal, the statin can be started, but the CK should be rechecked regularly. If the statin is over 10 times normal, the treatment should be stopped, renal function should be checked, and the CK should be checked every 2 weeks. If the CK is between 4 and 10 times the upper limit of normal without symptoms, the statin can be continued, but the CK should be monitored. If the CK is between 4 and 10 with symptoms, the statins should be stopped and reintroduced at a lower dose when the level becomes normal. If the CK remains elevated, myopathy should be considered and an alternative combination drug therapy or an alternative drug therapy should be continued.
With regard to muscle pain, this is a particular problem with statins because in most people the blood tests are normal and it is hard to know whether the muscle pain is causally related to statin or not. In a very small minority of people, actual rhabdomyolysis occurs with very high levels of CK, and, of course, the statin has to be stopped immediately and kidney function and liver function need to be monitored. There is an algorithm in the guideline explaining exactly how to approach muscle pain. Essentially, if the enzymes are normal, in general the statin can be continued.
There is a group of people—even with normal muscle enzymes—who just cannot take statins. Then the advice is to stop the statin for a while and reintroduce either another statin or extremely low-dose statin and build it up very slowly over a number of weeks. But these issues are spelled out in the algorithm in the guidelines.