A 72-year-old man comes to the physician complaining of 2 weeks of muscle cramps and stiffness in his legs. He also feels fatigued and has to rest after walking several blocks. His past medical history is significant for coronary artery disease, type 2 diabetes mellitus, paroxysmal atrial fibrillation, and hyperlipidemia.
The patient underwent coronary revascularization with placement of 2 drug-eluting stents in his left anterior descending artery 6 months ago. His medications include metformin, low-dose-aspirin, clopidogrel, metoprolol, valsartan, and atorvastatin. He was recently started on amiodarone due to recurrent episodes of highly symptomatic atrial fibrillation.
The patient's blood pressure is 129/72 mm Hg and pulse is 65/min. His body mass index is 30 kg/m². There is no muscle tenderness on physical examination. His muscle strength is 5/5 bilaterally and deep-tendon reflexes are 2+ and symmetrical bilaterally.
Laboratory results are as follows:

His atorvastatin is discontinued and his symptoms resolve completely within 4 weeks.
Which of the following is the best next step in management of this patient?

Question

A 72-year-old man comes to the physician complaining of 2 weeks of muscle cramps and stiffness in his legs. He also feels fatigued and has to rest after walking several blocks. His past medical history is significant for coronary artery disease, type 2 diabetes mellitus, paroxysmal atrial fibrillation, and hyperlipidemia.
The patient underwent coronary revascularization with placement of 2 drug-eluting stents in his left anterior descending artery 6 months ago. His medications include metformin, low-dose-aspirin, clopidogrel, metoprolol, valsartan, and atorvastatin. He was recently started on amiodarone due to recurrent episodes of highly symptomatic atrial fibrillation.
The patient's blood pressure is 129/72 mm Hg and pulse is 65/min. His body mass index is 30 kg/m². There is no muscle tenderness on physical examination. His muscle strength is 5/5 bilaterally and deep-tendon reflexes are 2+ and symmetrical bilaterally.
Laboratory results are as follows:

His atorvastatin is discontinued and his symptoms resolve completely within 4 weeks.
Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

11ec193a_9748_0664_853d_27df67ba3c6d_MD0002_00 This patient's presentation is consistent with statin myopathy, likely due to a drug-drug interaction between amiodarone and atorvastatin. Amiodarone decreases statin metabolism (especially simvastatin, lovastatin, and atorvastatin) through CYP3A4 inhibition in the liver, which can substantially increase the risk of muscle injury. Patients with suspected statin myopathy should discontinue the statin. After symptoms resolve, the patient may be given an alternate statin (eg, pravastatin, fluvastatin, rosuvastatin) with a lower risk of myopathy when taken with amiodarone (Choice B). Current guidelines recommend high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) for patients with known atherosclerotic cardiovascular disease (Choice A). Rosuvastatin is not metabolized by the cytochrome P-450 system and is less likely to interact with amiodarone. If rosuvastatin also is not tolerated, less potent statins (eg, pravastatin, fluvastatin) may be considered. There is also limited evidence from small studies that coenzyme Q10 may reduce the incidence of muscle toxicity. (Choice C) Ezetimibe would be an alternate therapy for lowering cholesterol if this patient could not tolerate any form of statin. However, clinical trials have not shown that ezetimibe significantly reduces the risk of coronary events. (Choice D) Gemfibrozil lowers triglycerides and raises high-density lipoprotein but is not as effective as statins in lowering low-density lipoprotein. In addition, gemfibrozil can also inhibit the metabolism of amiodarone and lead to possible side effects. Educational objective: Statin myopathy commonly occurs due to drug-drug interactions and usually resolves after discontinuing the statin. After resolution of myopathy, patients requiring aggressive cholesterol lowering should be restarted on an alternate statin with a lower myopathic potential (eg, rosuvastatin, pravastatin, fluvastatin). __________ References: Results of a safety initiative for patients on concomitant amiodarone and simvastatin therapy in a Veterans Affairs medical center. (http://www.ncbi.nlm.nih.gov/pubmed/20726676) Adverse events with concomitant amiodarone and statin therapy. (http://www.ncbi.nlm.nih.gov/pubmed/15860984) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. (http://www.ncbi.nlm.nih.gov/pubmed/18997196)

A 72-Year-Old Man Comes to the Physician Complaining of 2