The most widely prescribed cholesterol medication has come under scrutiny time and again over its possible effects on the liver and muscle. By Michael Lim

A PATIENT and her son came to my clinic one day looking rather upset. She had been told by a doctor that the cholesterol medication, 10 mg of simvastatin daily, that was prescribed to her will damage her body, including her liver and muscle and she should not take any cholesterol lowering medication called statins. I had to patiently explain the merits and safety of statin to this patient in great detail and after an hour, she and her son were fully convinced of the benefits of taking statin.

Time and time again, questions have arisen from patients about the safety of statins after they have read reports posted on the Internet.

Statins are the most widely prescribed cholesterol medication and they comprise a class of drugs which block the production of LDL cholesterol (LDL-C ) or “bad” cholesterol by the liver. The Internet has a mix of scholarly studies expounding on the merits of statins and anecdotal articles written by individuals who describe the demerits of statins, and it is not surprising for the lay person to be confused.

A recent publication in the Circulation Cardiovascular Quality and Outcomes journal, which compared how well the different statins were tolerated and their harmful effects, examined 135 randomised controlled studies conducted on about 250,000 subjects. The publication provided an extensive overview of the safety of statins and a comparison of the different statins based on data from studies in the last few decades.

Are statins beneficial?

Many studies have shown without the shadow of a doubt that statins, by lowering the LDL-C or “bad” cholesterol, will increase the likelihood of survival and reduce the risk of heart attacks and strokes. The benefits were seen even in those without pre-existing heart disease. It is estimated that for those taking statins over a four-year period, for every decrease of 40-mg/dL in the LDL-C, the risk of death from any cause is decreased by 9 per cent (for those with diabetes mellitus) to 13 per cent (for those without diabetes mellitus). These beneficial effects are apparent within the first year of taking statins.

Are statins well tolerated?

Interestingly, when statins as a group are compared to taking placebo (a tablet with no drug content which externally looks exactly like the drug-containing tablet), the likelihood of stopping medication as a result of perceived side effects was similar. In other words, whether you are taking a statin or a placebo, the likelihood of stopping the medication as a result of being unwell from the consumed tablet was similar.

When comparisons are made between individual statins, those on pravastatin and simvastatin are less likely to discontinue medication compared to those on atorvastatin and rosuvastatin. While most statins did not show a higher discontinuation rate when higher doses were prescribed when compared with placebo control, atorvastatin at higher than 20 mg daily dosage had significantly higher discontinuation rates.

Muscle aches and statins

Muscle and liver complaints are the two commonest concerns in those taking statins. Muscle ache is a complaint not infrequently mentioned by those on statins, with a reported incidence of about 2 per cent. However, for statins as a class, the studies showed that when patients were given either placebo or a statin without their knowledge of which tablet they were taking, there was no significant difference in the incidence of muscle aches between both groups. Among statins, those on simvastatin were less likely to complain of muscle aches compared to those on atorvastatin.

In relation to the possible effects of statins on muscle, physicians frequently check the blood level of the muscle enzyme, creatine kinase (CK), as a surrogate measure of the degree of muscle damage from statin consumption. The reported incidence of CK elevation was 0.6 per cent. Overall, as a class of drugs, statins do not appear to have a higher incidence of elevation of CK as compared to placebo. However among the statins, the reported incidence appears to be higher in some compared to others. Pitavastatin is more likely to cause CK elevation when compared to placebo and fluvastatin is more likely to cause CK elevation than all other statins except lovastatin. Some statins such as lovastatin and simvastatin can cause significant CK elevations at higher dosages.

The incidence of severe muscle ache or “myopathy” (defined as unexplained muscle weakness or pain with more than 10 times elevation of the CK level in the blood) is 0.02 per cent for those on simvastatin 20 mg daily and increases to 0.9 per cent for those on 80 mg daily.

The incidence of severe muscle cell damage or rhabdomyolysis (defined as severe muscle damage with more than 40 times elevation of the CK level in the blood) was 0 per cent for patients on 20 mg daily and about 0.4 per cent for those on 80 mg/day.

The likelihood of myopathy increases if the statin is given together with certain types of drugs. Gout patients, those requiring antibiotics, transplant patients, HIV patients and women starting hormone replacement therapy will need to have a discussion with the physicians regarding drug interactions with statins. In comparison, data from studies on rosuvastatin report an incidence of myopathy of 0.2 per cent to 0.4 per cent for dosages of five to 40 mg daily.

Simply put, the likelihood of serious adverse effects on muscle is extremely rare when low doses of statins are used and appears to be similar to the incidence seen when taking a placebo. However, the risk increases when high statin doses are used and when used with other drugs that have potential interactions with the statins.

This is the first of two parts on cholesterol-lowering medications