title: Prediction of cardiovascular event risk reduction from lipid changes associated with high potency dyslipidemia therapy.
abstract: BACKGROUND
  Epidemiological data suggests for every 1% reduction in LDL-C there is a corresponding 1-1.5% reduction in cardiovascular events (CVEs). Additionally, for every 2-3% increase in HDL-C there is a reduction in CVEs by 2-4% that is independent of LDL-C. With numerous treatment options for managing dyslipidemia, it is important to evaluate agents that result in the greatest reduction of CVEs.
  
  
  OBJECTIVE
  To compare current high-potency dyslipidemia pharmacotherapy with respect to changes in LDL-C and HDL-C and estimate risk reductions for CVEs.
  
  
  METHODS
  This study is an analysis of existing published studies for dyslipidemia products marketed in the US. Literature searches were conducted using Medline, International Pharmaceutical Abstracts, Embase, and CINAH to identify trials for niacin extended-release and lovastatin (NER/L); niacin extended-release and simvastatin (NER/S); rosuvastatin (R); and, ezetimibe/simvastatin (E/S) from database inception to 1 May 2009. Demographics and changes from baseline in LDL-C and HDL-C were abstracted and HDL-C to LDL-C change (%Delta-lipids) was created for each therapy. Using a previously validated model the percent reduction in CVEs was estimated for each treatment strategy.
  
  
  RESULTS
  Data for 177 treatment arms (120 unique reports), accounting for drug and dose were abstracted. The range in mean +/- SD %Delta-lipids depending on drug dose was: E/S, 58 +/- 6 to 67 +/- 3; R, 51 +/- 5 to 65 +/- 5; NER/L, 33 +/- 7 to 75 +/- 7; and NER/S, 48 to 77 +/- 4. Risk reductions were greatest for NER/statin combinations, with percent risk reductions greater than 77% for NER/S, 2000 mg/10 mg and 83% NER/S, 2000 mg/40 mg. Ignoring medication strengths, reductions in CVEs ranged from 58% for R, 60% for E/S, 61% for NER/L, and 72% for NER/S.
  
  
  CONCLUSIONS
  There are several potential limitations associated with this study including: publication bias, English only search, limited published studies with NER in combination with L or S, adherent populations, and aggregation of multiple populations.
  
  
  CONCLUSIONS
  The results of the analysis suggest that greater risk reductions in CVEs occur with combination therapies, especially those including niacin extended-release (NER). Up to an 83% risk reduction was estimated for the highest doses of NER and simvastatin (NER/S).
authors.affiliation: School of Pharmacy, University of Colorado, 258 Leland Creek Circle, Box 1941, Winter Park, CO 80482-1941, USA. S.L.Charland@ATT.net
authors.forename: Scott L
authors.initials: SL
authors.lastname: Charland
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Malone
mesh_terms: D000465:Algorithms; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control*; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D040242:Risk Reduction Behavior; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D001384:Azetidines; D000960:Hypolipidemic Agents; D008055:Lipids; D009525:Niacin; D008148:Lovastatin; D019821:Simvastatin; D000069438:Ezetimibe