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The most common side effect of statins is mild myalgia, which occurs in 5% to 10% of patients taking the medication. Severe side effects such as rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM) are rare. Other associated side effects include diabetes mellitus and neurological complaints. Lowering statin dose or switching lipid-lowering protocols may be needed.
Abstract
This abstract is available on the publisher’s site.
Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are “statin-associated symptoms” because they are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving mediations. SAMS is the most frequent SAS, and mild myalgia may affect 5% to 10% of statin users. Clinically important muscle symptoms, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM), are rare. Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is largely anecdotal. Management of SAS requires making the possible diagnosis, altering or discontinuing the statin treatment, and using alternative lipid-lowering therapy.
Statin-Associated Symptoms
This review article goes through in detail all of the statin-associated side effects. The authors have categorized the side effects, and the three key ones that we all deal with are muscle symptoms, diabetes, and neurocognitive effects.
Statin-associated muscle symptoms (SAMS) is the most common side effect; it affects some 10% to 25% of patients; however, even a formal definition is difficult and the severity can range from myopathy to myalgia to myositis and rhabdomyolysis. Creatine kinase (CK) levels can be used to categorize severity, but some patients have SAMS without any increase in CK. Also, after exercise, the CK levels can be above 10,000. So, CK is not statin-specific. Therefore, the recommendation on diagnosing SAMS is to use a combination of factors such as symmetrical muscle symptoms, CK levels, and temporal relationship with the start of statin therapy in order to make a clinical diagnosis of SAMS.
Unfortunately, co-enzyme Q10, which has been popularized as a treatment of SAMS, has only been studied in small trials, and it is difficult to prove whether it is actually working or not; hence, it is hard to recommend it for our patients. However, all the guidelines suggest to re-challenge the patient with statin therapy with either a different agent, reduced dose, or less frequent dosing.
For statin-associated diabetes, the data were quite strong. There is a small increase in diabetes in statin-treated patients. Yet, in the recent HOPE 3 study, patients were randomized to ensure that the metabolic parameters were equally divided between the statin and placebo groups. With this balanced randomization, there was no increase in diabetes in the statin-treated group after 5.6 years. So, perhaps statins do not increase diabetes. Regardless of the connection or no connection, all of the guidelines say that, even if the statin does increase diabetes, the reductions in CV events far outweighs the risk, and hence statins should still be used.
Finally, statins and the brain association has caught the media’s attention. One theory is that statins are reducing brain cholesterol levels, hence creating cognitive and memory issues. Unfortunately, most of the studies did not do formal mental testing but were self-reported cases of memory issues. Perhaps we, as clinicians, should do a baseline mini mental status test on our patients and then periodically check their mental function. This is good general practice and we might be able to detect any changes that are related to statin therapy. For now, statins should still be used to reduce vascular disease and hence, in theory, should reduce dementia.
I think this review nicely details what we know and what we don’t know about statin therapies. We do need to be vigilant and keep an eye out for these side effects, but at the same time we need to encourage our patients to stay on their statins in order to prevent CV events and death.