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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n\u003Cp id=\u0022p-1\u0022\u003EThe OSLER extension studies randomized patients to receive standard of care or standard of care plus evolocumab. At 1 year, evolocumab lowered low-density lipoprotein cholesterol by 61% and demonstrated preliminary evidence that this may reduce the risk of cardiovascular events. Evolocumab was well tolerated across all gradients of achieved low-density lipoprotein cholesterol levels.\u003C\/p\u003E\n\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eevolocumab\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOSLER trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiovascular risk\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elow-density lipoprotein cholesterol\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eproprotein convertase subtilisinkexin type 9 inhibitor\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology \u0026amp; cardiovascular medicine clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n\n\u003Cp id=\u0022p-2\u0022\u003EMarc S. Sabatine, MD, MPH, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA, presented data on the OSLER studies [Sabatine MS et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2015], 2 open-label, randomized extension studies of evolocumab phase 2 and phase 3 trials. OSLER showed that evolocumab, a proprotein convertase subtilisinkexin type 9 (PCSK9) inhibitor, effectively decreased low-density lipoprotein cholesterol (LDL-C) levels and reduced cardiovascular (CV) outcomes. The drug was well tolerated, with no gradient of adverse events (AEs) across all levels of minimum achieved LDL-C.\u003C\/p\u003E\n\u003Cp id=\u0022p-3\u0022\u003EAvailable data on evolocumab, a fully human monoclonal antibody against PCSK9, demonstrate its ability to lower LDL-C by about 60% on top of statin therapy; additionally, the drug has been well tolerated by patients [Raal FJ et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2015; Robinson JG et al. \u003Cem\u003EJAMA\u003C\/em\u003E. 2014; Stein EA et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E. 2014]. However, the effect of evolocumab on CV outcomes of patients was previously undefined.\u003C\/p\u003E\n\u003Cp id=\u0022p-4\u0022\u003EPatients were randomized in a 2:1 ratio to receive evolocumab plus standard of care (n\u2005=\u20052976) or standard of care alone (n\u2005=\u20051489). Evolocumab was administered by subcutaneous injections of either 140 mg every 2 weeks or 420 mg once monthly. Median follow-up was 11.1 months (interquartile range, 11.0 to 12.8); the vast majority of patients (96%) completed follow-up and 7% discontinued evolocumab early. The primary end point was the incidence of AEs, and the secondary outcome was the percent change in LDL-C levels. A prespecified, exploratory analysis of adjudicated CV clinical outcomes was performed.\u003C\/p\u003E\n\u003Cp id=\u0022p-5\u0022\u003EBaseline characteristics were similar between treatment arms. The average age was 58 years, 80% of patients had at least 1 CV risk factor, and 25% had known vascular disease. A majority (70%) of patients were receiving statins, mostly (62%) of high or moderate intensity.\u003C\/p\u003E\n\u003Cp id=\u0022p-6\u0022\u003ETreatment with evolocumab resulted in a 61% reduction in LDL-C at 12 weeks (95% CI, 59% to 63%; \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001) as compared to standard therapy. The absolute reduction in LDL-C was 73 mg\/dL (95% CI, 71 to 76), with a median achieved LDL-C of 48 mg\/dL. All lipid parameters were significantly affected, including decreased non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, lipoprotein(a), and triglycerides, and increased HDL-C and apolipoprotein A1 (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001 for all).\u003C\/p\u003E\n\u003Cp id=\u0022p-7\u0022\u003EUsing a composite CV end point, including death, coronary events, cerebrovascular events, and heart failure requiring hospitalization, the Kaplan-Meier 1-year rates of CV events were 0.95% for patients receiving evolocumab and 2.18% for patients receiving standard of care alone (HR, 0.47; 95% CI, 0.28 to 0.78; \u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.003). Separation of the Kaplan-Meier plots was evident after 2 to 3 months of follow-up.\u003C\/p\u003E\n\u003Cp id=\u0022p-8\u0022\u003EThis decrease in CV end points was consistent across all types of CV outcomes and was consistent across all patient subgroups with no heterogeneity of effect. Rates of AEs were balanced between treatment arms, except for neurocognitive AEs, which were higher in the evolocumab arm although they were low in both arms (\u0026lt;\u20051%). Notably, these events did not appear related to achieved LDL-C.\u003C\/p\u003E\n\u003Cp id=\u0022p-9\u0022\u003EFurther study on evolocumab is underway with the FOURIER trial, for which results are expected in 2017. Dr Sabatine concluded that in the interim, the OSLER data support the potential for PCSK9 inhibition with evolocumab to reduce the risk of CV outcomes through lowered LDL-C levels.\u003C\/p\u003E\n\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/5\/10.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzl1bq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}