Efficacy and safety of evolocumab in reducing lipids and cardiovascular events
- PMID: 25773607
- DOI: 10.1056/NEJMoa1500858
Efficacy and safety of evolocumab in reducing lipids and cardiovascular events
Abstract
Background: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in short-term studies. We conducted two extension studies to obtain longer-term data.
Methods: In two open-label, randomized trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ("parent trials") of evolocumab. Regardless of study-group assignments in the parent trials, eligible patients were randomly assigned in a 2:1 ratio to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for a median of 11.1 months with assessment of lipid levels, safety, and (as a prespecified exploratory analysis) adjudicated cardiovascular events including death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure. Data from the two trials were combined.
Results: As compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). Most adverse events occurred with similar frequency in the two groups, although neurocognitive events were reported more frequently in the evolocumab group. The risk of adverse events, including neurocognitive events, did not vary significantly according to the achieved level of LDL cholesterol. The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003).
Conclusions: During approximately 1 year of therapy, the use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis. (Funded by Amgen; OSLER-1 and OSLER-2 ClinicalTrials.gov numbers, NCT01439880 and NCT01854918.).
Comment in
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Lowering LDL cholesterol is good, but how and in whom?N Engl J Med. 2015 Apr 16;372(16):1564-5. doi: 10.1056/NEJMe1502192. Epub 2015 Mar 15. N Engl J Med. 2015. PMID: 25773740 No abstract available.
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PCSK9 inhibitors reduce cardiovascular events, preliminary data show.BMJ. 2015 Mar 17;350:h1508. doi: 10.1136/bmj.h1508. BMJ. 2015. PMID: 25782694 No abstract available.
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Dyslipidaemia. Assessing the efficacy and safety of evolocumab and alirocumab.Nat Rev Cardiol. 2015 May;12(5):261. doi: 10.1038/nrcardio.2015.51. Epub 2015 Mar 31. Nat Rev Cardiol. 2015. PMID: 25824512 No abstract available.
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PCSK9 Inhibitors and Cardiovascular Events.N Engl J Med. 2015 Aug 20;373(8):773-4. doi: 10.1056/NEJMc1508222. N Engl J Med. 2015. PMID: 26287856 No abstract available.
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PCSK9 Inhibitors and Cardiovascular Events.N Engl J Med. 2015 Aug 20;373(8):774-5. doi: 10.1056/NEJMc1508222. N Engl J Med. 2015. PMID: 26295078 No abstract available.
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