1. When paired with statin therapy, evolocumab greatly reduced patient low-density lipoprotein cholesterol (LDL-C) levels compared to placebo or ezetimibe.
2. Evolocumab paired with statin therapy reduced LDL-C levels in patients independent of statin type or treatment intensity across the three most common statins.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Nearly 14% of Americans over 20 years of age suffer from high LDL-C levels, for which statins are the primary treatment. High levels of LDL-C are associated with increased risk of atherosclerotic cardiovascular disease and in patient cases where statins fail to adequately lower LDL-C, alternative measures are often advised. A number of non-statin therapies have been shown to reduce LDL-C levels in patients, including ezetimibe – the most commonly prescribed non-statin therapy for hypercholesterolemia. Recent concerns have arisen as to the effectiveness and safety of Ezetimibe and alternative therapies are being explored.
This study examined the capacity of evolocumab, a human monoclonal antibody against PCSK9, for reducing LDL-C levels in patients. When paired with statin therapy, evolocumab was more effective than ezetimibe or placebos in lowering patient LDL-C after 12 weeks. This finding held across three different statin types, two evolocumab dose regimes (every two weeks or monthly), and variable initial LDL-C levels. The brevity of the patient trial did not allow for assessment of the long-term effects of evolocumab on cardiovascular disease and overall patient health. Additional trials to investigate long-term safety and efficacy of evolocumab will further assess its value as a therapy for hypercholesterolemia.
In-Depth [randomized controlled trial]: This trial was a phase 3 multicenter randomized controlled trial investigating the efficacy of evolocumab in combination with statins for lowering LDL-C levels. Between January and December of 2013, 1896 patients with primary hypocholesterolemia and mixed dyslipidemia underwent non-statin therapy and were included in the analysis. Prior to the study, 29% of patients were on intensive statin therapy, while 41% were on nonintensive statin therapy and 30% were on no statin therapy. Previous treatments were halted and patients were segregated, via a 2-step randomization process, into 24 treatment groups that encompassed variations of statin type (atorvastatin, simvastatin, rosuvastatin), statin dose intensity (moderate or high), non-statin therapy type (evolocumab, ezetimibe or placebo), and evolocumab dosage frequency (every two weeks or monthly). LDL-C levels at the mean of weeks 10 and 12 and at week 12 were attained by the Friedewald formula or in very low LDL cases (< 40mg/dL) by preparative ultracentrifugation. For coprimary endpoints, LDL-C end values were compared to baseline values to provide mean percent change from baseline. Two-sided significance testing was used to compare results across treatment groups.
Monthly dosing of evolocumab reduced LDL-C levels (mean of week 10 and 12) by 62% to 65% from baseline values and by 63% to 75% from placebo values. Within a statin treatment group (atorvastatin), evolocumab reduction of LDL-C was significantly greater than placebo or ezetimibe (P < 0.001). Where evaluated, findings were similar across statin therapy variables (type and intensity), evolocumab dosage schedule, and LDL-C measurement (week 12 or mean of week 10 and 12). Adverse event frequency and type did not vary greatly across non-statin therapies.
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