Myopathy associated with statin therapy

The literature concerning statin-induced myopathy is poor, with many of the reports coming from cardiologists, epidemiologists and pathologists with no expertise in the field of muscle disorders; for example, to define myositis on the basis of myalgia and elevated serum creatine kinase (CK), without histological evidence of inflammatory changes, is inappropriate and confusing [1]. Most reports suggest that myopathy is secondary to metabolic factors, although the significance of lowered levels of CoQ remains uncertain [2]. The most dramatic complication is that of a necrotizing myopathy, presumed to be metabolic in origin, without evidence of primary inflammation. There have been few reports of a true inflammatory myopathy complicating statin therapy.

The reports of Needham [3] and Wahl [4] relate to patients who appear to have developed a myopathy whilst on a statin, which then progressed or persisted despite discontinuation of the statin. Some of the patients had features of myositis. But there must remain the possibility that the patients described had a pre-existing, but asymptomatic, myopathy. In none of the 16 patients described had they had their CK measured before starting a statin.

Nor presumably had a detailed neurological history been taken. I am aware of several patients thought to have had a statin-induced myopathy who in fact had clearly had a pre-existing myopathy.

After commencing a statin it is likely that the patient will be encouraged to report symptoms such as myalgia, and many patients will read, avidly, the information sheet with the tablets which includes details of side-effects. Alerted, the physician will then check the CK. Finding it elevated the statin will be stopped. If the CK remains elevated it will be assumed, possibly wrongly, that the statin is to blame. What will not be known, in most cases, is the CK level before starting therapy. Two cases illustrate this:

The first was a 73-year-old woman with ischaemic heart disease. She was put on a statin. She reported myalgia and her CK was found to be elevated. The drug was stopped, her complaint persisted, and her CK remained elevated. Taking a detailed history she had had a lifelong history of myalgia, her CK had been recorded to be elevated when she had presented on several occasions with angina, but attributed to her heart. She was shown to have McArdle’s disease.

A 50-year-old woman was put on a statin because of a high cholesterol and family history of vascular disease. On follow-up the doctor elicited a history of myalgia. Her CK was elevated, and remained elevated when the statin was stopped. On more detailed enquiry the myalgia had started before commencing the statin. She was found to be hypothyroid and on replacement therapy her CK returned to normal and cholesterol level fell.

In such cases, measuring CK before commencing the statin would have been helpful. I believe that an argument can be put forward for such to be standard practice, and was disappointed by the conclusion of a recent America review [5] which stated “The Muscle Expert Panel did not consider a baseline CK level absolutely necessary. Baseline CK values may be useful to determine whether increased CK levels on statin therapy are due to the drug or to other causes, but similar information can be obtained by statin withdrawal”. As the above cases illustrate the latter is not true and in patients such as those reported by Needham and Wahl we are left with uncertainty as to whether or not the statins really are the cause of the myopathy.

Statins arrived, hailed as a major medical therapeutic triumph. There is currently the inevitable questioning about benefits versus side-effects and many vociferous campaigners against their use. With respect to statin-induced myopathy what we need is quality evidence, and that is lacking.