title: Efficacy, safety and effect on biomarkers related to cholesterol and lipoprotein metabolism of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg vs. simvastatin 40 or 80 mg plus ezetimibe 10 mg in high-risk patients: Results of the GRAVITY randomized study.
abstract: OBJECTIVE
  Combination therapy may help high-risk patients achieve low-density lipoprotein cholesterol (LDL-C) goals. Impact of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg (RSV10/EZE10 and RSV20/EZE10) has not been fully characterized previously. GRAVITY (NCT00525824) compared efficacy, safety and effect on biomarkers of RSV10/EZE10 and RSV20/EZE10 vs. simvastatin 40 mg and 80 mg plus EZE10 (SIM40/EZE10 and SIM80/EZE10) in patients with coronary heart disease (CHD) or CHD risk equivalent.
  
  
  METHODS
  Adult patients (n = 833) were randomized to RSV10/EZE10, RSV20/EZE10, SIM40/EZE10 or SIM80/EZE10. Following a 6-week dietary lead-in, patients received 6 weeks' statin monotherapy followed by same statin dose plus ezetimibe for 6 more weeks. Primary endpoint was LDL-C change from baseline to 12 weeks.
  
  
  RESULTS
  Significantly greater (p < 0.05) reductions in LDL-C and other atherogenic lipids were observed with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. A significantly greater proportion of patients achieved LDL-C goals of <100 mg/dl and <70 mg/dl with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. LDL-C was reduced ∼10-14% further with combination therapy vs. monotherapy. Statin monotherapy reduced cholesterol and bile acid synthesis biomarkers, ezetimibe reduced β-sitosterol (sterol absorption marker), and combination therapy achieved additive reductions in lipoprotein-associated phospholipase A2 mass and activity, free cholesterol and 7-ketocholesterol. Safety profiles of rosuvastatin/ezetimibe and simvastatin/ezetimibe combinations were comparable.
  
  
  CONCLUSIONS
  Co-administration of rosuvastatin 10 or 20 mg plus ezetimibe achieved significant improvements in lipid profiles in high-risk patients vs. simvastatin 40 or 80 mg plus ezetimibe.
authors.affiliation: Department of Medicine, Baylor College of Medicine and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: cmb@bcm.tmc.edu.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Department of Medicine, Baylor College of Medicine and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA.
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.affiliation: Department of Medicine, Baylor College of Medicine and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA.
authors.forename: Joe L
authors.initials: JL
authors.lastname: Raya
authors.affiliation: AstraZeneca, Wilmington, DE, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Cain
authors.affiliation: Keele University, Keele, UK.
authors.forename: Mike K
authors.initials: MK
authors.lastname: Palmer
authors.affiliation: AstraZeneca R&D Mölndal, Mölndal, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Björn W
authors.initials: BW
authors.lastname: Karlson
mesh_terms: D000042:Absorption; D000328:Adult; D050197:Atherosclerosis / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood* / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000069438:Ezetimibe; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage; D012306:Risk; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000008:administration & dosage; D012855:Sitosterols / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D001384:Azetidines; D015415:Biomarkers; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008074:Lipoproteins; D011743:Pyrimidines; D012855:Sitosterols; D013449:Sulfonamides; C025473:gamma-sitosterol; D000068718:Rosuvastatin Calcium; D019821:Simvastatin; D000069438:Ezetimibe
keywords: Ezetimibe; Hypercholesterolemia; Low-density lipoprotein cholesterol; Rosuvastatin; Simvastatin