title: Eligibility for PCSK9 treatment in 734 Hypercholesterolemic patients referred to a regional cholesterol treatment center with LDL cholesterol ≥ 70 mg/dl despite maximal tolerated cholesterol lowering therapy.
abstract: BACKGROUND
  LDL cholesterol (LDLC) lowering has been revolutionized by PCSK9 inhibitors, Alirocumab (Praluent) and Evolocumab (Repatha), approved as adjuncts to maximally tolerated cholesterol lowering therapy in heterozygous (HeFH) or homozygous (HoFH) familial hypercholesterolemia, and/or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient.
  
  
  METHODS
  We applied FDA and insurance eligibility criteria for PCSK9 inhibitor use in 734 hypercholesterolemic patients serially referred over 3 years who then received ≥ 2 months maximally tolerated LDLC lowering therapy with follow up LDLC ≥ 70 mg/dl, and in 50 patients approved by insurance for PCSK9 inhibitors. We documented the percentage of patients with HeFH and/or CVD who met FDA and insurance criteria for PCSK9 inhibitor therapy using LDLC goal-based guidelines.
  
  
  RESULTS
  Of 734 patients with LDLC ≥ 70 mg/dl after ≥ 2 months maximally tolerated LDLC lowering therapy, 220 (30%) had HeFH and/or CVD with LDLC > 100 mg/dl, meeting FDA-insurance criteria for PCSK9 inhibitor therapy. Another 66 (9%) patients were statin intolerant, without HeFH or CVD. Of the 50 patients whose PCSK9 inhibitor therapy was approved for insurance coverage, 45 (90%) had LDLC > 100 mg/dl after ≥ 2 months on maximally tolerated LDLC lowering therapy. Seventeen of these 50 patients (34%) had HeFH without CVD (LDLC on treatment 180 ± 50 mg/dl), 15 (30%) had CVD without HeFH (LDLC on treatment 124 ± 26 mg/dl), 14 (28%) had both HeFH and CVD (LDLC on treatment 190 ± 53 mg/dl), and 4 (8%) had neither HeFH nor CVD (LCLC 142 ± 11 mg/dl).
  
  
  CONCLUSIONS
  Of 734 patients referred for LDLC reduction, with LDLC ≥ 70 mg/dl after ≥ 2 months on maximally tolerated therapy, 220 (30%) had HeFH and/or CVD with LDLC > 100 mg/dl, meeting FDA-insurance criteria for PCSK9 inhibitor therapy as an adjunct to diet-maximally tolerated cholesterol lowering therapy in HeFH or CVD. If 30% of patients with high LDLC and HeFH-CVD are eligible for PCSK9 inhibitors, then specialty pharmaceutical pricing models (~$14,300/year) will collide with tens of millions of HeFH-CVD patients. We speculate that if there was a 50 % reduction in CVD, then there would be savings of $245 billion, in the middle of the range of estimated PCSK9 inhibitor costs of $185-342 billion. Whether the health care savings arising from the anticipated reduction of CVD events by PCSK9 inhibitors justify their extraordinary costs in broad population use remains to be determined.
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA. cjglueck@mercy.com.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA.
authors.forename: Parth
authors.initials: P
authors.lastname: Shah
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA.
authors.forename: Naila
authors.initials: N
authors.lastname: Goldenberg
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA.
authors.forename: Marloe
authors.initials: M
authors.lastname: Prince
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lee
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA.
authors.forename: Vybhav
authors.initials: V
authors.lastname: Jetty
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Kumar
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Goldenberg
authors.affiliation: From the Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Cincinnati, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy; D008078:Cholesterol, LDL / Q000097:blood*; D004608:Eligibility Determination; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy; D007354:Insurance, Major Medical; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D000091362:PCSK9 Inhibitors; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D000071449:Proprotein Convertase 9
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D000091362:PCSK9 Inhibitors; D015842:Serine Proteinase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab; C571059:alirocumab
keywords: Atherosclerotic cardiovascular disease (CVD); Heterozygous familial hypercholesterolemia (HeFH); LDL cholesterol (LDLC); PCSK9 inhibitors