Statins and muscle pain

A recently e-published article from a team of researchers at a Harvard teaching hospital has suggested that statin users are more likely to have musculoskeletal pain. [1]

Statins (3-hydroxy-3-methylglutaryl coenzyme A or HMG-CoA inhibitors) are a class of medications that are used to lower cholesterol levels in people with or at risk of cardiovascular disease. They work by inhibiting an HMG-CoA enzyme, stimulating LDL receptors, resulting in more low-density lipoprotein (LDL - often known as "bad cholesterol") being taken from the bloodstream and a decrease in blood cholesterol levels.

Muscle effects are the most commonly reported side effects of statins, with muscle cramps, myalgia (muscle pain), myopathy (muscle problems with the primary symptom of muscle weakness due to dysfunction of the muscle fibers), rhabdomyolysis (the breakdown of muscle fibers) and arthralgias (joint pains) being reported. Non-urgent myalgias are relatively common, with rhabdomyolysis being rare.

However, in placebo-controlled trials the incidence of muscle pain is often similar for placebo and active control groups.

This study sought to evaluate whether statin use was associated with a higher prevalence of musculoskeletal pain in a nationally (USA) representative sample. [1]

Data from the US National Health and Nutrition Examination Survey (NHANES) 1999-2002 was used. This gave 3,580 adult "participants", 40 years of age or over, without arthritis, who were interviewed at home and examined in a mobile examination center. They were asked about sociodemographic characteristics, health conditions, medication use, and musculoskeletal pain. Height, weight, blood pressure, ankle brachial index, and cholesterol were measured. The ankle brachial index is a measure of the reduction in blood pressure between arteries in the upper arms and the ankles, and as such, it is used to detect evidence of blockages in the circulatory system. [1]

The study analysed the data to determine the prevalence and adjusted odds ratios of any musculoskeletal pain and musculoskeletal pain in 4 different anatomical regions (neck/upper back, upper extremities, lower back, and lower extremities) by statin use during the last 30 days. [1]

There were 402 statin users in the data used and the study found that 22% of these reported musculoskeletal pain in at least 1 anatomical region during the 30 days previous to the data being collected, compared to 16.7% of those who did not use a statin. Compared to persons who did not use statins, those who used statins had multivariable-adjusted odds ratios of 1.50 for any musculoskeletal pain, 1.59 for lower back pain, and 1.50 for lower extremity pain. [1]

The researchers concluded that musculoskeletal pain is common in adults 40 years of age or over, without arthritis, and that:

"In this nationally representative sample, statin users were significantly more likely to report musculoskeletal pain."

One of the researchers from the team that carried out this study has also co-authored another paper that was published this month in the journal Pharmacogenomics. In this it is suggested that a gene required for muscle atrophy is implicated in the pathophysiology of statin-induced muscle injury, such as rhabdomyolysis. [3]

Statin use may be problematic for Fibromyalgia Syndrome patients because of the risk of increased pain. [4] However, an article published earlier this year suggests that the risk of myalgia and other potentially treatment-limiting muscle effects can be reduced through: proper monitoring; statin dosage reduction, discontinuation, and rechallenge; and the use of treatment alternatives, such as statins which are less likely to cause side effects. Statins can thus be used for their cardiovascular benefits whilst minimising the risk of muscle effects. [5]

References:

1. Buettner C, Davis RB, Leveille SG, Mittleman MA, Mukamal KJ. Prevalence of musculoskeletal pain and statin use. J Gen Intern Med. 2008 Aug;23(8):1182-6. Epub 2008 May 1.
2. Silva MA, Swanson AC, Gandhi PJ, Tataronis GR. Statin-related adverse events: a meta-analysis. Clin Ther. 2006 Jan;28(1):26-35.
3. Buettner C, Lecker SH. Molecular basis for statin-induced muscle toxicity: implications and possibilities. Pharmacogenomics. 2008 Aug;9(8):1133-42.
4. Mascitelli L, Pezzetta F, Goldstein MR. Detrimental effect of statin therapy in women with fibromyalgia. Arch Intern Med. 2008 Jun 9;168(11):1228-9.
5. Jacobson TA. Toward "pain-free" statin prescribing: clinical algorithm for diagnosis and management of myalgia. Mayo Clin Proc. 2008 Jun;83(6):687-700.