title: Clinical Profile of Statin Intolerance in the Phase 3 GAUSS-2 Study.
abstract: OBJECTIVE
  Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects Study (GAUSS-2; NCT 01763905).
  
  
  METHODS
  GAUSS-2 compared evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) to ezetimibe in hypercholesterolemic patients who discontinued statin therapy due to statin-associated muscle symptoms (SAMS). GAUSS-2 was a 12-week, double-blind, placebo-controlled, randomized study that enrolled patients with elevated LDL-C who were either not on a statin or able to tolerate only a low-dose due to SAMS. Patients had received ≥2 statins and were unable to tolerate any statin dose or increase in dose above a specified weekly dose due to SAMS.
  
  
  RESULTS
  Three hundred seven patients (mean [SD] age, 62 [10] years; 54 % males) were randomized 2:1 (evolocumab:ezetimibe). Mean (SD) LDL-C was 4.99 (1.51) mmol/L. Patients had used ≥2 (100 %), ≥3 (55 %), or ≥4 (21 %) statins. Coronary artery disease was present in 29 % of patients. Statin-intolerant symptoms were myalgia in 80 % of patients, weakness in 39 %, and more serious complications in 20 %. In 98 % of patients, SAMS interfered with normal daily activity; in 52 %, symptoms precluded moderate exertion.
  
  
  CONCLUSIONS
  Evaluation of the GAUSS-2 trial population of statin-intolerant patients demonstrates that most patients were high risk with severely elevated LDL-C and many had statin-associated muscle symptoms that interfered with their quality of life.
authors.affiliation: Preventive Cardiology and Rehabilitation, Cleveland Clinic, 9500 Euclid Ave. Desk JB1, Cleveland, OH, USA. chol@ccf.org.
authors.forename: Leslie
authors.initials: L
authors.lastname: Cho
authors.affiliation: Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave. Desk JB1, Cleveland, OH, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rocco
authors.affiliation: Wesley Medical Centre, 40 Chasely Street, Auchenflower, Brisbane, 4066, QLD, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Colquhoun
authors.affiliation: Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Building 65 Missenden Road, Camperdown, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Sullivan
authors.affiliation: Cardiometabolic Disorders, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, Box 1030, New York, NY, 10029, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Rosenson
authors.affiliation: Amgen (Europe) GmbH, Dammstrasse 23, 6300, Zug, Switzerland.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Dent
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Allen
authors.initials: A
authors.lastname: Xue
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Scott
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Wasserman
authors.affiliation: Department of Vascular Medicine, F4.211, Academic Medical Center, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Stroes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced*; D000091362:PCSK9 Inhibitors; D055815:Young Adult; D000071449:Proprotein Convertase 9
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D000069438:Ezetimibe; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab
keywords: Cholesterol; Evolocumab; Ezetimibe; LDL; Myalgia; Statin intolerance