title: Determining When to Add Nonstatin Therapy: A Quantitative Approach.
abstract: BACKGROUND
  Costs and uncertainty about the benefits of nonstatin therapies limit their use.
  
  
  OBJECTIVE
  The authors sought to identify patients who might benefit from the addition of a nonstatin to background statin therapy.
  
  
  METHODS
  We performed systematic reviews of subgroup analyses from randomized trials and observational studies with statin-treated participants to determine estimated 10-year absolute risk of atherosclerotic cardiovascular disease (ASCVD) and to define high-risk and very high-risk patients. We used the relative risk reductions for the addition of a nonstatin to lower low-density lipoprotein (LDL-C) used to determine the number needed to treat (NNT) to prevent 1 ASCVD event over 5 years for each patient group and to allow comparisons with 5-year cost analyses.
  
  
  RESULTS
  The 10-year ASCVD risk is at least 30% (very high risk) for statin-treated participants with clinical ASCVD and comorbidities, and 20% to 29% (high risk) for those with ASCVD without comorbidities or who have heterozygous familial hypercholesterolemia. Adding ezetimibe to reduce low-density LDL-C by 20% would provide a 5-year NNT ≤50 for very high-risk patients with LDL-C ≥130 mg/dl or for high-risk patients with LDL-C ≥190 mg/dl, and an NNT ≤30 for very high-risk patients with LDL-C ≥160 mg/dl. Adding a PCSK9 monoclonal antibody to lower LDL-C by at least 50% would provide an NNT ≤50 for very high-risk and high-risk patients with LDL-C ≥70 mg/dl, and an NNT ≤30 for very high-risk and high-risk patients with an LDL-C ≥130 mg/dl.
  
  
  CONCLUSIONS
  Adding ezetimibe or PCSK9 monoclonal antibodies to maximally tolerated statin therapy may be cost effective in very high-risk and high-risk patients, depending on baseline LDL-C levels.
authors.affiliation: Departments of Epidemiology and Medicine, University of Iowa, Iowa City, Iowa. Electronic address: jennifer-g-robinson@uiowa.edu.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Roeland
authors.initials: R
authors.lastname: Huijgen
authors.affiliation: Department of Primary Care and Public Health, Imperial College, London, United Kingdom.
authors.forename: Kausik
authors.initials: K
authors.lastname: Ray
authors.affiliation: Departments of Epidemiology and Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Jane
authors.initials: J
authors.lastname: Persons
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Chapel Hill, North Carolina.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pencina
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000191:economics; D003362:Cost-Benefit Analysis; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: PCSK9 inhibitors; cost; ezetimibe; nonstatins; statins