MUSCULOSKELETAL SYMPTOMS ARE MOST COMMON
Musculoskeletal symptoms are the most common AEs reported by patients who are taking statins.5 These range from muscle weakness, fatigue, and pain to (rarely) rhabdomyolysis—a life-threatening condition characterized by severe muscle pain, muscle weakness, a 10-fold increase in creatine kinase (CK), and increased serum creatinine, often with myoglobinuria.5
Patients with myopathy—an umbrella term for any muscle disease—may report stiffness, weakness, tenderness, soreness, cramping, or heaviness. Symptoms are usually symmetrical and often involve the proximal limbs and trunk.6 Studies indicate that exercise increases the risk for statin-induced myalgia—muscle pain or weakness without an increase in CK—and that patients taking statins are more prone to exercise-related injury.7,8
A baseline CK is recommended for patients with an increased risk for muscular disorders.1 Risk factors include a personal or family history of statin intolerance or muscle disease, age older than 75, low levels of vitamin D, and concomitant use of medications that may increase the risk for myopathy (see Table 1).1 Routine monitoring of CK is not recommended, but CK levels should be obtained for those who exhibit muscle symptoms while on statin therapy.1
What the studies show
The incidence of myalgia reported in clinical studies is highly variable, ranging from less than 1% to 20%.1,9,10 The ACC/AHA guideline reports only one additional case of myopathy per 10,000 statin users compared with those on placebo and cites a rhabdomyolysis occurrence rate of less than 0.06% over five years.1
A 2006 systematic review estimated the absolute risk for rhabdomyolysis to be 3.4 per 100,000 person-years, but the incidence was 10 times higher for patients taking both a statin and gemfibrozil.11 (See Table 212,13 for more on drug interactions.) But both the meta-analysis cited earlier4 and a previous systematic review14 (35 RCTs and > 74,000 patients) found that statins as a class do not increase the incidence of myalgia or rhabdomyolysis.
Differences in the way muscular disorders are defined has been suggested as one reason for the discrepancies.10 In addition, many clinical trials exclude patients at higher risk for statin-associated AEs, such as those with renal or hepatic insufficiency, prior muscular complaints, poorly controlled diabetes, or potential drug interactions.1
An FDA advisory. In a safety communication last updated in February 2012, the FDA cautioned against starting patients on the highest dose of simvastatin (80 mg).15 The warning is based on a large study (N = 12,064) that found an increased risk for myopathy (0.9%) and rhabdomyolysis (0.2%) in patients on the
80-mg dose versus those taking 20 mg (0.02% and 0%, respectively).16
With the ACC/AHA now recommending intensive therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) to achieve an LDL reduction greater than 50% for many patients,1 it is important to be aware that this risk is specific to simvastatin. A recent meta-analysis of studies directly comparing patients receiving intensive statin therapy with those on low to moderate doses did not find any increased risk in rhabdomyolysis associated with more intensive therapy when those taking 80-mg simvastatin were excluded.17
The bottom line: Although rhabdomyolysis is rare, its severity—a fatality rate of 10%11—makes it critical to educate patients about the disorder and instruct them to stop taking the statin and call the office immediately if they develop severe muscle pain or weakness.
Recommend CoQ10 for statin-induced myopathy
Although the exact mechanism of statin-induced myopathy is unknown, the most likely explanation is a depletion of coenzyme Q10 (CoQ10), which has negative effects on mitochondrial energy production.18 While studies using CoQ10 to treat this AE have been small and had mixed results, the overall evidence suggests that it decreases the development and/or severity of symptoms.18-20
In fact, CoQ10 supplementation is the only treatment that has shown promise in treating statin-induced muscle symptoms.18-20 Doses of about 100 mg bid have been found to be beneficial and safe; no clinically relevant AEs have been seen with doses lower than 300 mg/d.18,20,21 A large placebo-controlled study is currently evaluating a 600 mg/d dose of CoQ10 in patients with statin-induced myopathy.19
CASE
On his next visit, Mr L. reports a new ache in his left shoulder and upper back, which he describes as mild but annoying. He also tells you his memory seems to be getting worse and that he has developed an odd tingling in his hands. These symptoms began about a month after he started the medications, Mr L. says. He also began a new exercise program, but his BMI is unchanged.
On examination, you find the affected shoulder and upper back modestly and diffusely tender to palpation but with no decline in strength. Mr L.’s BP has fallen to
134/84 mm Hg, and his fasting glucose is 105 mg/dL. Lab tests reveal an LDL of 144 mg/dL and HDL of 36 mg/dL, A1C of 6.1%, ALT of 105 U/L, AST of 61 U/L, and a normal CK.
You recommend 100 mg CoQ10 bid. Because it is available only OTC, you advise the patient to look for a product whose purity and potency have been verified by an external source, such as the US Pharmacopeial Convention. You also prescribe metformin 500 mg bid for insulin resistance, refer the patient to a nutritionist and diabetes specialist, and order tests to evaluate his other symptoms.
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