American Heart Association: Side Effects of Statins Overview and Context

Underestimated Statins?

Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, known as statins, have significantly contributed to the reduction of cardiovascular diseases in recent decades. However, these diseases remain the most common cause of death in developed countries. Despite the positive effects proven by numerous randomized studies and meta-analyses, adherence to statin treatment is not ideal. The occurrence of symptoms, interpreted by patients or doctors as adverse events associated with statin use, leads to the discontinuation of treatment in up to 10% of patients in the United States. Other patients stop therapy merely due to the fear of side effects.

AHA Report on Statin Safety

The American Heart Association (AHA) issued a new report at the end of 2018, summarizing the safety and risks of statins based on findings from randomized studies, meta-analyses, and observational studies. The report clearly shows that the occurrence of serious adverse events with statin use is rare.

Serious Adverse Events

Statin myopathy (defined for this work as otherwise unexplained muscle pain or weakness associated with statins and accompanied by a creatine kinase level exceeding ten times the upper limit of normal) occurs in less than 0.1% of treated patients. Rhabdomyolysis, which can cause renal failure, was observed in 0.01% of patients. Discontinuing statin therapy usually leads to the disappearance of muscle impairment symptoms, except for the rare autoimmune myopathy, which can progress even after stopping treatment and may require immunotherapy.

Serious hepatotoxic effects of statins occur in approximately 0.001% of patients.

Additionally, although the evidence is not yet convincing, statin use may slightly increase the risk of hemorrhagic stroke in patients with a history of cerebrovascular disease. However, this potential risk is significantly outweighed by the reduced risk of ischemic stroke.

Less Serious Adverse Events

Non-serious muscle symptoms are frequently complained about by patients during statin treatment and affect their compliance. Studies show that only less than 1% of patients taking statins actually experience these symptoms due to pharmacotherapy.

An isolated increase in transaminases above three times the upper limit of normal occurs in about 1% of treated patients, is usually transient, and is not accompanied by other symptoms of liver damage.

Statins slightly increase the risk of diabetes mellitus diagnosis, especially in individuals with numerous risk factors for developing DM. In the general treated population, statin-induced diabetes occurs in approximately 0.2% of treated patients per year.

Adverse Events Not Proven to be Associated with Statin Treatment

A number of other adverse events have been associated with statin use, such as the development of Alzheimer’s or Parkinson’s disease, cancer, tendinitis, peripheral neuropathy, or cataracts. However, no causal relationship between statin treatment and these conditions has been proven. Some studies report effects of statins on testosterone levels, but the changes were not clinically significant.

Conclusions of the AHA Report

In conclusion, the AHA states that the benefits of statin use significantly outweigh the potential risks if statins are indicated for the patient according to current guidelines.

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Source: Newman C. B., Preiss D., Tobert J. A. et al. Statin safety and associated adverse events: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2019; 39 (2): e38–e81, doi: 10.1161/ATV.0000000000000073.