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From trials in which patients\u2019 LDL cholesterol was already well controlled on a statin, adding ezetimibe incrementally reduced CVD end points, whereas adding a fibrate or niacin showed no incremental benefit. Among emerging nonstatins, monoclonal antibodies against proprotein convertase subtilisin kexin type 9 added to a statin and given for \u226478 weeks showed preliminary evidence of reductions in CVD outcomes. Although these promising early findings contributed to the recent approval of these agents in Europe and in North America, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits. Other nonstatin agents recently approved in the United States include lomitapide and mipomersen, which both act via distinctive LDL receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift toward more assertive LDL-lowering treatment, using both statins and nonstatins initiated earlier in appropriately selected patients.<\/jats:p>","DOI":"10.1161\/atvbaha.115.306442","type":"journal-article","created":{"date-parts":[[2015,9,17]],"date-time":"2015-09-17T00:18:47Z","timestamp":1442449127000},"page":"2269-2280","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["Nonstatin Low-Density Lipoprotein\u2013Lowering Therapy and Cardiovascular Risk Reduction\u2014Statement From\n                    <i>ATVB<\/i>\n                    Council"],"prefix":"10.1161","volume":"35","author":[{"given":"Robert A.","family":"Hegele","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada (R.A.H.); Nemours Cardiac Center, A. I. duPont Hospital for Children, Wilmington, DE (S.S.G.); Irving Institute for Clinical and Translational Research, Department of Medicine, Columbia University, New York, NY (H.N.G.); Department of Medicine and Biochemistry, Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (R.M.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel S.","family":"Gidding","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada (R.A.H.); Nemours Cardiac Center, A. I. duPont Hospital for Children, Wilmington, DE (S.S.G.); Irving Institute for Clinical and Translational Research, Department of Medicine, Columbia University, New York, NY (H.N.G.); Department of Medicine and Biochemistry, Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (R.M.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry N.","family":"Ginsberg","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada (R.A.H.); Nemours Cardiac Center, A. I. duPont Hospital for Children, Wilmington, DE (S.S.G.); Irving Institute for Clinical and Translational Research, Department of Medicine, Columbia University, New York, NY (H.N.G.); Department of Medicine and Biochemistry, Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (R.M.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"McPherson","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada (R.A.H.); Nemours Cardiac Center, A. I. duPont Hospital for Children, Wilmington, DE (S.S.G.); Irving Institute for Clinical and Translational Research, Department of Medicine, Columbia University, New York, NY (H.N.G.); Department of Medicine and Biochemistry, Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (R.M.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick J.","family":"Raal","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada (R.A.H.); Nemours Cardiac Center, A. I. duPont Hospital for Children, Wilmington, DE (S.S.G.); Irving Institute for Clinical and Translational Research, Department of Medicine, Columbia University, New York, NY (H.N.G.); Department of Medicine and Biochemistry, Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (R.M.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Rader","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada (R.A.H.); Nemours Cardiac Center, A. I. duPont Hospital for Children, Wilmington, DE (S.S.G.); Irving Institute for Clinical and Translational Research, Department of Medicine, Columbia University, New York, NY (H.N.G.); Department of Medicine and Biochemistry, Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (R.M.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer G.","family":"Robinson","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada (R.A.H.); Nemours Cardiac Center, A. I. duPont Hospital for Children, Wilmington, DE (S.S.G.); Irving Institute for Clinical and Translational Research, Department of Medicine, Columbia University, New York, NY (H.N.G.); Department of Medicine and Biochemistry, Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (R.M.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francine K.","family":"Welty","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada (R.A.H.); Nemours Cardiac Center, A. 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