Risks and Benefits of Statin Therapy

Risks and Benefits of Statin Therapy

The increased media attention on the adverse effects associated with statin therapy has unfortunately led to statin therapy discontinuation, nonadherence to therapy or concerns about starting statin therapy. In outpatient clinics, health care providers frequently encounter concern regarding the safety of statins from patients. Herein, lies a brief overview of the risks and benefits of statin therapy.


What are the benefits of statin therapy?

High-quality evidence from randomised trials shows that statin therapy reduces the risk of major cardiovascular events (such as cardiac death, heart attack, stroke and the need for revascularisation i.e. coronary stenting or coronary artery bypass grafting) by about one-quarter for each mmol/L reduction in LDL cholesterol during each year that it continues to be taken. The absolute benefits of statin therapy depend on an individual’s absolute risk of cardiovascular events and the absolute reduction in LDL cholesterol that is achieved.

For example, lowering LDL cholesterol by 2 mmol/L with an effective low-cost statin regimen (e.g. atorvastatin 40mg daily, costing €4.76 per month) for 5 years in 10 000 patients would typically prevent a major cardiovascular event (such as a heart attack or stroke) in about 1,000 patients (i.e. 10% absolute benefit) with pre-existing cardiac disease (secondary prevention) and in 500 patients (i.e. 5% absolute benefit) who are at increased risk but have no yet had a cardiovascular event (primary prevention). Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term. 


What are the risks of statin therapy?

The most common side effect of long-term statin therapy are muscle aches and pains (known as Statin Associated Muscle Symptoms, abbreviated as SAMS), which occur in 10-29% of patients in observational studies, although this figure is thought to be an overestimation. In randomised controlled trials, just 1-2% of patients complained of SAMS.  This discrepancy may be due to a nocebo effect, which is observed when subjective adverse events are more likely to be attributed to a treatment that is believed to cause harm.

New-onset diabetes mellitus and, probably, haemorrhagic stroke (particularly among patients who had a previous haemorrhagic stroke) are other potential serious adverse events. Typically, treatment of 10,000 patients for 5 years with an effective regimen (e.g. atorvastatin 40mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50-100 new cases of diabetes mellitus, and 5-10 haemorrhagic strokes. Statin therapy may cause SAMS in up to about 50-100 patients per 10,000 treated for 5 years. Liver failure occurs in 1 in 100,000 patients and therefore it would be unlikely to be observed in the example above. The large-scale evidence available from randomised trials indicated that it is unlikely that any further serious side effects await discovery.

It is therefore of concern that exaggerated claims about side effects of statins may be responsible for its underuse among individuals at increased risk of cardiovascular events. Whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily (or never even started) can be catastrophic.


Author: Dr Cróchán O’Sullivan, MD, PhD, FESC