Definitions
Myalgia
Myalgia is defined as pain or soreness and/or weakness in skeletal muscles in the absence of serum creatinine elevation. Symptoms of myalgia are quite variable and include cramping, pain, aches, tenderness, soreness, stiffness, heaviness, and weakness either at rest or only during physical exertion. Muscle cramping at night only is not likely statin related. Myopathy is defined as complaints of myalgia, plus elevation in serum CK (creatinine kinase) greater than 10 times the upper limit of normal (ULN).
Rhabdomyolysis is defined as CK elevation > 10,000 U/L, in accord with the definition currently used by the FDA, regardless of whether the patient has experienced a change in renal function, because such a CK level places the patient at high risk for acute renal failure. A second component is CK > 10X the ULN with worsening renal function and/or a requirement for medical intervention with intravenous hydration therapy, along with myalgia.
Incidence
Incidence of muscle symptoms or signs (CK = creatinine kinase elevations) is the most prevalent and important adverse effect of statin therapy. The occurrence of serious muscle toxicity with currently marketed statins is rare.
Myopathy occurs in five patients per 100,000 person-years (in clinical trials, the rate is 1.5%-3.0%, most often without CK elevation and at an equivalent rate in patients given placebo). In the practice setting, the range is 0.3%-33%. The higher rate may occur partly because statin-intolerant patients and high-risk patients are likely to be excluded from clinical trials.
Rhabdomyolysis occurs in 1.6 patients per 100,000 person-years.
1. Muscle symptoms or increased CK due to statin therapy is rare. Rule out other causes including increased physical activity, trauma, falls,
accidents, seizure, shaking chills, hypothyroidism, infections, carbon monoxide poisoning, polymyositis, dematomyositis, alcohol abuse and
drug abuse (cocaine, amphetamines, heroin or PCP).
2. Baseline pretreatment CK levels are not necessary except in high-risk patients. Risk factors for muscle toxicity include advanced age and
frailty, small body frame, deteriorating renal function, infection, untreated hypothyroidism, interacting drugs, perioperative patients and alcohol
abuse.
3. It is not necessary to measure CK levels in asymptomatic patients during treatment. Marked increases are rare and usually related to physical
exertion or other causes.
4. Patient education regarding the muscle symptoms to watch for and report is essential for all patients taking statins.
5. Measure CK levels in symptomatic patients to help decide whether to continue therapy or alter dose.
6. Discontinue statin in patients with intolerable muscle symptoms with or without CK elevation when other etiologies are ruled out.
Once asymptomatic, resume the same or different statin at the same or lower dose. Recurrence of symptoms with multiple statins and doses
requires initiation of other lipid-altering therapy.
Patient counseling regarding intensification of therapeutic lifestyle changes (reduced intake of saturated fats and cholesterol, increased
physical activity, and weight control) should be an integral part of management in all patients with statin-associated intolerable muscle
symptoms.
7. If patient is asymptomatic or has tolerable muscle complaints but CK less than 10X the ULN, continue statin at same or lower dose while
monitoring symptoms.
8. If patient develops rhabdomyolysis (CK greater than 10,000 IU/L or CK greater than 10X the ULN with elevation in serum creatinine, OR
requiring IV hydration therapy), stop statin. Hospitalization may be required. Once recovered, the risk vs. benefit of therapy should be carefully
reconsidered.
(Jacobson, 2008 [R]; McKenney, 2006 [R]) |
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