A 63-year-old man is seen in the office 2 weeks after a ST-elevation myocardial infarction (MI). A former smoker with hypertension, he was discharged on atorvastatin 80mg daily, dual anti-platelet therapy, long-acting metoprolol, and an ACE inhibitor. One year before the acute MI, he was prescribed simvastatin 40 mg which was then increased to simvastatin 80 mg. He stopped the simavastatin 80 mg 2 weeks later after developing muscle cramps in his legs. At that time he was also on a calcium channel blocker for his hypertension. Although he has no muscle symptoms since he started the atorvastatin 80 mg, he is concerned about having had muscle cramps in the past on a statin and would like to decrease the atorvastatin to 20 mg daily.
Which of the following statements is the best answer?
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The correct answer is: b. Systematic meta-analyses of randomized clinical trials support using an intensive statin dose such as atorvastatin 80 mg/day over a moderate intensity statin. He should stay on atorvastatin 80 mg.
Individuals with clinical atherosclerotic cardiovascular disease (ASCVD) are in a statin benefit group, and if ≤75 years of age, they should be treated with a high intensity statin unless conditions are present that may increase the risk of adverse effects. An additional reduction in ASCVD events from a high intensity statin was shown specifically in individuals with acute coronary syndromes in the PROVE-IT trial where those assigned to atorvastatin 80 mg/day a greater reduction in ASCVD events than those assigned to pravastatin 40 mg daily after 2 years of treatment. An additional ASCVD risk reduction benefit was also observed in 2 randomized controlled trials (RCTs) of atorvastatin 80 mg compared to either atorvastatin 10 mg or simvastatin 20-40 mg in individuals with chronic coronary heart disease (TNT and IDEAL). In these trials, there was no lower limit to LDL–C for eligibility; therefore, individuals with clinical ASCVD should be treated with a statin regardless of the LDL–C level. Although he did have muscle symptoms on simvastatin 80 mg, he was able to tolerate simvastatin 40 mg without difficulty. It is therefore reasonable to initiate atorvastatin 80 mg with patient instructions to monitor for muscle symptoms.
Although CK may be useful at baseline in certain high-risk individuals or in those with a history of statin myopathy, the CK should not be routinely measured. In the statin RCTs, CK elevations occurred with similar frequencies in the statin and placebo/control groups. A CK should be performed if the patient complains of severe muscle pain or weakness. This patient may have an SLC01B1 deficiency to explain the interaction between simvastatin 80 mg/day and the calcium channel blocker that may have caused his muscle symptoms. He was never rechallenged to determine whether the muscle aches were indeed caused by the simvastatin 80 mg. On 12/15/11, the FDA indicated that simvastatin 80 mg should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle injury. They emphasized that simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug.
On 2/28/12, the FDA determined, based on all available data, including the RCT data reviewed by the Expert Panel, that "all currently marketed statins appear to be associated with a very low risk of serious liver injury and that routine periodic monitoring of serum alanine aminotransferase (ALT) does not appear to detect or prevent serious liver injury in association with statins."
Thus, neither routine CK nor liver panel tests are required. Nonetheless, some patients may experience myalgias with statins. If these recur in this patient now on atorvastatin, after a wash-out period a dose reduction could be contemplated at that time, or an attempt with another statin, such as rosuvastatin. If symptoms persist after a reasonable statin-free interval (2 weeks or more) other causes of myalgia should be considered.
References
LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005; 352:1425-1435.
Pedersen TR, Faergeman O, Kastelein JJP, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: The IDEAL Study: A randomized controlled trial. JAMA. 2005; 294:2437-2445.
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004; 350:1495-1504.
Cholesterol Treatment Trialists Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. The Lancet. 2010; 376:1670-1681.
Dale KM, White CM, Henyan NN, Kluger J, Coleman CI. Impact of Statin Dosing Intensity on Transaminase and Creatine Kinase. Am J Med. 2007; 120(8):706-712.
The Search Collaborative Group. SLCO1B1 Variants and Statin Myopathy – A Genome Wide Study. N Engl J Med 2008; 359: 789-99.
FDA Drug and Safety information downloaded Nov 1, 2013: http://www.fda.gov/drugs/drugsafety/ucm256581.htm
http://www.fda.gov/drugs/drugsafety/ucm293101.htm
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