title: Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease.
abstract: OBJECTIVE
  Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were recently approved for lowering low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia (FH) or atherosclerotic cardiovascular disease (ASCVD) and have potential for broad ASCVD prevention. Their long-term cost-effectiveness and effect on total health care spending are uncertain.
  
  
  OBJECTIVE
  To estimate the cost-effectiveness of PCSK9 inhibitors and their potential effect on US health care spending.
  
  
  METHODS
  The Cardiovascular Disease Policy Model, a simulation model of US adults aged 35 to 94 years, was used to evaluate cost-effectiveness of PCSK9 inhibitors or ezetimibe in heterozygous FH or ASCVD. The model incorporated 2015 annual PCSK9 inhibitor costs of $14,350 (based on mean wholesale acquisition costs of evolocumab and alirocumab); adopted a health-system perspective, lifetime horizon; and included probabilistic sensitivity analyses to explore uncertainty.
  
  
  METHODS
  Statin therapy compared with addition of ezetimibe or PCSK9 inhibitors.
  
  
  METHODS
  Lifetime major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or stroke), incremental cost per quality-adjusted life-year (QALY), and total effect on US health care spending over 5 years.
  
  
  RESULTS
  Adding PCSK9 inhibitors to statins in heterozygous FH was estimated to prevent 316,300 MACE at a cost of $503,000 per QALY gained compared with adding ezetimibe to statins (80% uncertainty interval [UI], $493,000-$1,737,000). In ASCVD, adding PCSK9 inhibitors to statins was estimated to prevent 4.3 million MACE compared with adding ezetimibe at $414,000 per QALY (80% UI, $277,000-$1,539,000). Reducing annual drug costs to $4536 per patient or less would be needed for PCSK9 inhibitors to be cost-effective at less than $100,000 per QALY. At 2015 prices, PCSK9 inhibitor use in all eligible patients was estimated to reduce cardiovascular care costs by $29 billion over 5 years, but drug costs increased by an estimated $592 billion (a 38% increase over 2015 prescription drug expenditures). In contrast, initiating statins in these high-risk populations in all statin-tolerant individuals who are not currently using statins was estimated to save $12 billion.
  
  
  CONCLUSIONS
  Assuming 2015 prices, PCSK9 inhibitor use in patients with heterozygous FH or ASCVD did not meet generally acceptable incremental cost-effectiveness thresholds and was estimated to increase US health care costs substantially. Reducing annual drug prices from more than $14,000 to $4536 would be necessary to meet a $100,000 per QALY threshold.
authors.affiliation: Department of Medicine, Center for Vulnerable Populations, University of California, San Francisco2Department of Medicine, University of California, San Francisco3Department of Epidemiology and Biostatistics, University of California, San Francisco4Center.
authors.forename: Dhruv S
authors.initials: DS
authors.lastname: Kazi
authors.affiliation: Division of General Internal Medicine, Columbia University Medical Center, New York, New York7College of Physicians and Surgeons, Columbia University, New York, New York.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Moran
authors.affiliation: Department of Medicine, Center for Vulnerable Populations, University of California, San Francisco2Department of Medicine, University of California, San Francisco8Division of General Internal Medicine, Zuckerberg San Francisco General Hospital, San Franci.
authors.forename: Pamela G
authors.initials: PG
authors.lastname: Coxson
authors.affiliation: Department of Medicine, Center for Vulnerable Populations, University of California, San Francisco2Department of Medicine, University of California, San Francisco.
authors.forename: Joanne
authors.initials: J
authors.lastname: Penko
authors.affiliation: Institute for Clinical and Economic Review, Boston, Massachusetts.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Ollendorf
authors.affiliation: Institute for Clinical and Economic Review, Boston, Massachusetts.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Pearson
authors.affiliation: Department of Medicine, University of California, San Francisco.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Tice
authors.affiliation: Department of Medicine, Center for Vulnerable Populations, University of California, San Francisco.
authors.forename: David
authors.initials: D
authors.lastname: Guzman
authors.affiliation: Department of Medicine, Center for Vulnerable Populations, University of California, San Francisco2Department of Medicine, University of California, San Francisco3Department of Epidemiology and Biostatistics, University of California, San Francisco8Divisi.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bibbins-Domingo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000191:economics; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000191:economics* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D000069438:Ezetimibe / Q000191:economics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors*; D019057:Quality-Adjusted Life Years; D012697:Serine Endopeptidases; D035501:Uncertainty; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D000069438:Ezetimibe; C577155:evolocumab; C571059:alirocumab