1. Among patients with muscle-related statin intolerance, evolocumab reduced LDL-C levels significantly more than ezetimibe.
2. Evolocumab and ezetimibe had similar rates of muscle-related adverse events when compared to statins.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Statin therapy has been shown to be effective in reducing cholesterol levels in patients with hypercholesterolemia. However, it has been estimated that between 5% and 29% of patients on a statin will experience muscle-related side effects. Other, non-statin drugs, like ezetimibe are recommended for use in these patients, although their efficacy has been limited. Newer, non-statin drugs, including the PCSK9 inhibitor, evolocumab, may be more useful in lowering cholesterol in statin-intolerant patients. Thus, this double-blinded randomized controlled study compared the effectiveness and tolerability of ezetimibe and evolocumab in patients who experienced statin-related muscle side effects. The results showed that evolocumab reduced LDL-C levels significantly more than ezetimibe. Other lipid panel measurements were also significantly decreased in the evolocumab cohort, including non-HDL-C, ApoB, and total cholesterol.
This trial represents the most comprehensive study analysis of cholesterol levels in statin-intolerant patients, and suggests that PCSK9 inhibitors may be a useful alternative to statin medication in patients with muscle-related adverse events. However, this study was limited by its relatively small cohort, short follow-up, and limited number of adverse events, and more studies are needed to determine the full clinical utility of evolocumab.
In-Depth [randomized controlled trial]: This study aimed to quantify the effects of two non-statin medications, ezetimibe and evolocumab, in patients who experienced muscle-related adverse events to traditional statin therapy. The primary outcome measure was the change in LDL-C levels from baseline after 24 weeks of therapy. In the first phase of this study, 492 patients were given both a statin challenge and placebo over intervening weeks. A total of 209 (42.6%) patients experienced muscle symptoms while on a statin and not the placebo, and were eligible for the second phase of the study. During this second phase, 199 of the above qualified patients, and 19 others who had a history of elevated CK on statin therapy were randomized in a 2:1 ratio to receive evolocumab 420 mg monthly IV or ezetimibe 10 mg daily by mouth. LDL-C levels for the mean of weeks 22 and 24 were 183 mg/dL (95%CI 167.4 to 198.6 mg/dL; least-squares mean percent change from baseline -16.7%, 95%CI -20.5% to -12.9%) for ezetimibe and 103.6 mg/dL (95%CI 92.5 to 114.8 mg/dL; mean percent change -54.5%, 95%CI -57.2% to -51.8%) for evolocumab. The mean difference in LDL-C when comparing evolocumab to ezetimibe was -37.8% (95%CI -42.3% to -33.3%, p < 0.001). Muscle-related adverse events occurred in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients.
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