title: 2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis?
abstract: BACKGROUND
  The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether percent low-density lipoprotein cholesterol (LDL-C) reduction or attained LDL-C levels add incremental prognostic value to statin dose is not known.
  
  
  METHODS
  Patients in the Treating to New Targets (TNT), Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL), and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trials (patient-level data) randomized to a statin arm (atorvastatin 80 mg/10 mg or simvastatin 20 mg) were chosen. Patients were divided into groups based on attained LDL-C levels (≤70 vs >70 mg/dL) and percent LDL-C reduction (≥50% vs <50%). Primary outcome was major cardiovascular event defined as death due to coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke. Incremental prognostic value was assessed by using a forward conditional Cox proportional hazards model. Two models were tested: Model 1: Step 1 statin dose; Step 2 add attained LDL-C levels (continuous variable); Step 3 add percent LDL-C reduction (continuous variable). Model 2: Steps 2 and 3 were reversed.
  
  
  RESULTS
  Among 13,937 patients included in this study, percent LDL-C reduction added incremental prognostic value over both statin dose and attained LDL-C levels (global chi-square increased from 3.64 to 26.1 to 47.5; P <.0001). However, attained LDL-C level did not provide incremental prognostic value over statin dose and percent LDL-C reduction (global chi-square increased from 3.64 to 47.5 to 47.5; P <.0001 and .94, respectively). Among patients with attained LDL-C ≤70 mg/dL, those with percent LDL-C reduction of <50% had a significantly higher risk of primary outcome (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.16-1.97; P = .002) and stroke (HR, 2.07; 95% CI, 1.46-2.93; P <.0001) and a numerically higher risk of death (HR, 1.37; 95% CI, 0.98-1.90; P = .06) when compared with the group with percent LDL-C reduction of ≥50%.
  
  
  CONCLUSIONS
  In patients with atherosclerotic cardiovascular disease, percent LDL-C reduction provides incremental prognostic value over statin dose and attained LDL-C levels. However, the attained LDL-C level does not provide additional prognostic value over statin dose and percent LDL-C reduction.
authors.affiliation: New York University School of Medicine, New York, NY. Electronic address: sripalbangalore@gmail.com.
authors.forename: Sripal
authors.initials: S
authors.lastname: Bangalore
authors.affiliation: Pfizer, New York, NY.
authors.forename: Rana
authors.initials: R
authors.lastname: Fayyad
authors.affiliation: Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Pfizer, New York, NY.
authors.forename: Rachel
authors.initials: R
authors.lastname: Laskey
authors.affiliation: Paris-Diderot Sorbonne University, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
authors.affiliation: Pfizer, New York, NY.
authors.forename: David A
authors.initials: DA
authors.lastname: DeMicco
authors.affiliation: San Francisco General Hospital, San Francisco, Calif.
authors.forename: David D
authors.initials: DD
authors.lastname: Waters
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000517:prevention & control; D000069059:Atorvastatin / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011379:Prognosis; D019821:Simvastatin / Q000008:administration & dosage*
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin; D019821:Simvastatin
keywords: LDL-C targets; Percent reduction; Statins