Applied Evidence
Statin therapy: When to think twice
While statins lower the risk of morbidity and mortality for millions of Americans, recent findings help clarify when a statin—or a statin and...
PRACTICE RECOMMENDATIONS
› Advise patients starting statin therapy to stop taking the medication and call your office immediately if they develop severe muscle pain or weakness, as statins are associated with a small increased risk of rhabdomyolysis. B
› Obtain a baseline creatine kinase level for patients with an increased risk of musculoskeletal disorders; routine monitoring is needed only for those who experience muscle pain or weakness while on statin therapy. C
› Prescribe statins for patients with chronic kidney or liver disease when indicated; statin therapy is not associated with an increased risk of renal or hepatic failure. B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
CASE › Carl L, a 57-year-old obese patient (body mass index [BMI] >40) who had not been to a doctor in a decade, comes to see you after a health fair screening revealed dyslipidemia (low-density lipoprotein [LDL] cholesterol, 188 mg/dL; high-density lipoprotein cholesterol [HDL], 32 mg/dL; total cholesterol, 240 mg/dL; triglycerides, 100 mg/dL). His blood pressure (BP) is 146/90 mm Hg and his fasting glucose is 101 mg/dL. Labs drawn that day reveal a glycated hemoglobin (HbA1c) of 5.9%, alanine aminotransferase (ALT) of 45 U/L, and aspartate aminotransferase (AST) of 62 U/L. In taking his history, you discover that Mr. L also has a prominent family history of heart disease.
Mr. L agrees to take a low-dose statin, and you prescribe atorvastatin 10 mg and a thiazide diuretic. You advise the patient to contact you immediately if he develops significant myalgia, jaundice, dark urine, or symptoms of hyperglycemia such as excessive thirst or urination, and schedule a follow-up visit in 8 weeks.
Long recognized as the bedrock of hyperlipidemia therapy, statins achieved even greater prominence when the American College of Cardiology/American Heart Association (ACC/AHA) issued a new cholesterol guideline1 late last year. The ACC and AHA now recommend statins for a wider range of patients, often at a higher starting dose. (To read about the controversy the recommendations generated, see “The new cholesterol guideline: Beyond the headlines,” J Fam Pract. 2013;62:730.)
Based on the new recommendations, the use of statins is likely to rise.2 (A statin [rosuvastatin] is already the nation’s most widely prescribed medication.2) Thus, it is more important than ever for physicians to be knowledgeable about the risks associated with statins and able to assess the benefits of therapy for individual patients.
A 2013 retrospective cohort study of >100,000 patients on statins found that 17% developed adverse effects (AEs). Therapy was withheld, at least temporarily, for 10% of study participants (60% of those experiencing AEs).3 At the same time, the authors of a large meta-analysis (135 randomized controlled trials [RCTs] and >240,000 patients) reported that AEs associated with statins as a class were uncommon. The meta-analysis also found that the overall discontinuation rate for statin users—5.7%—was not significantly different from that of patients on placebo.4
Such discrepancies regarding particular risks as well as the overall incidence of AEs and discontinuation rates make the evidence difficult to sort out. We created this update with that in mind.
Musculoskeletal symptoms are most common
Skeletal muscle symptoms are the most common AEs reported by patients 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 usually are symmetrical and often involve the proximal limbs and trunk.6 Studies indicate that exercise increases the risk of 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 of muscular disorders.1 Risk factors include a personal or family history of statin intolerance or muscle disease, age >75 years, low levels of vitamin D, and concomitant use of medications that may increase the risk of myopathy (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 <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 <.06% over 5 years.1