title: A 52-week placebo-controlled trial of evolocumab in hyperlipidemia.
abstract: BACKGROUND
  Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab.
  
  
  METHODS
  We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52.
  
  
  RESULTS
  Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain.
  
  
  CONCLUSIONS
  At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks. (Funded by Amgen; DESCARTES ClinicalTrials.gov number, NCT01516879.).
authors.affiliation: From the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town (D.J.B.), and TREAD Research, Cardiology Unit, Department of Internal Medicine, Tygerberg Hospital and Stellenbosch University, Parow (L.B.) - both in South Africa; Center for Clinical and Basic Research, Pardubice (T.H.), and Center of Preventive Cardiology, Third Department of Internal Medicine, Charles University, Prague (R.C.) - both in the Czech Republic; Bethesda Health Research Center, Bethesda, MD (M.B.); Lillestol Research, Fargo, ND (M.J.L.); Midwest Institute for Clinical Research, Indianapolis (P.D.T.); Sterling Research Group (E.R.) and Metabolic and Atherosclerosis Research Center (E.A.S.) - both in Cincinnati; Jacksonville Center for Clinical Research, Jacksonville, FL (M.J.K.); Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston (C.M.B.); Amgen, Thousand Oaks, CA (M.L.M., J.B.K., R.S., S.M.W.); and Amgen, Uxbridge, United Kingdom (K.T.).
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Blom
authors.forename: Tomas
authors.initials: T
authors.lastname: Hala
authors.forename: Michael
authors.initials: M
authors.lastname: Bolognese
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lillestol
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Toth
authors.forename: Lesley
authors.initials: L
authors.lastname: Burgess
authors.forename: Richard
authors.initials: R
authors.lastname: Ceska
authors.forename: Eli
authors.initials: E
authors.lastname: Roth
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Koren
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Monsalvo
authors.forename: Kate
authors.initials: K
authors.lastname: Tsirtsonis
authors.forename: Jae B
authors.initials: JB
authors.lastname: Kim
authors.forename: Rob
authors.initials: R
authors.lastname: Scott
authors.forename: Scott M
authors.initials: SM
authors.lastname: Wasserman
authors.forename: Evan A
authors.initials: EA
authors.lastname: Stein
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000069059:Atorvastatin; D001384:Azetidines / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood*; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000178:diet therapy / Q000188:drug therapy*; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000276:immunology; D011758:Pyrroles / Q000627:therapeutic use; D012697:Serine Endopeptidases / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001384:Azetidines; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D000069438:Ezetimibe; C577155:evolocumab