Deepak L Bhatt1, Andrew H Briggs2, Shelby D Reed3, Lieven Annemans4, Michael Szarek5, Vera A Bittner6, Rafael Diaz7, Shaun G Goodman8, Robert A Harrington9, Keiko Higuchi10, Florence Joulain11, J Wouter Jukema12, Qian H Li13, Kenneth W Mahaffey9, Robert J Sanchez13, Matthew T Roe14, Renato D Lopes15, Harvey D White16, Andreas M Zeiher17, Gregory G Schwartz18, Ph Gabriel Steg19. 1. Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: dlbhattmd@post.harvard.edu. 2. London School of Hygiene and Tropical Medicine, London, United Kingdom. 3. Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. 4. Ghent University, Ghent, Belgium. 5. Downstate School of Public Health, State University of New York, Brooklyn, New York. 6. Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama. 7. Estudios Clínicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina. 8. Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada; St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 9. Department of Medicine, Stanford University Medical Center, Stanford, California. 10. Sanofi, Bridgewater, New Jersey. 11. Sanofi, Chilly-Mazarin, France. 12. Leiden University Medical Center, Leiden, the Netherlands. 13. Regeneron, Tarrytown, New York. 14. Verana Health, San Francisco, California. 15. Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. 16. Green Lane Cardiovascular Services Auckland City Hospital, Auckland, New Zealand. 17. Department of Medicine III, Goethe University, Frankfurt am Main, Germany. 18. Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado. 19. Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Université de Paris, French Alliance for Cardiovascular Trials, Institut National de la Santé et de la Recherche Médicale U1148, Paris, France; National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom. Electronic address: https://twitter.com/gabrielsteg.
Abstract
BACKGROUND: Cholesterol reduction with proprotein convertase subtilisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute coronary syndrome remains uncertain. OBJECTIVES: This study sought to determine whether further cholesterol reduction with alirocumab would be cost-effective in patients with a recent acute coronary syndrome on optimal statin therapy. METHODS: A cost-effectiveness model leveraging patient-level data from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was developed to estimate costs and outcomes over a lifetime horizon. Patients (n = 18,924) had a recent acute coronary syndrome and were on high-intensity or maximum-tolerated statin therapy, with a baseline low-density lipoprotein cholesterol (LDL-C) level≥70 mg/dl, non-high-density lipoprotein cholesterol ≥100 mg/dl, or apolipoprotein B≥80 mg/l. Alirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Alirocumab was blindly titrated to 150 mg if LDL-C remained ≥50 mg/dl or switched to placebo if 2 consecutive LDL-C levels were <15 mg/dl. Incremental cost per quality-adjusted life-year (QALY) was determined with the addition of alirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels ≥100 mg/dl and <100 mg/dl. RESULTS: Across the overall population recruited to the ODYSSEY OUTCOMES trial, using an annual treatment cost of US$5,850, the mean overall incremental cost-effectiveness ratio was US$92,200 per QALY (base case). The cost was US$41,800 per QALY in patients with baseline LDL-C ≥100 mg/dl, whereas in those with LDL-C <100 mg/dl the cost per QALY was US$299,400. Among patients with LDL-C ≥100 mg/dl, incremental cost-effectiveness ratios remained below US$100,000 per QALY across a wide variety of sensitivity analyses. CONCLUSIONS: In patients with a recent acute coronary syndrome on optimal statin therapy, alirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C ≥100 mg/dl but less economic value with LDL-C <100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402).
RCT Entities:
BACKGROUND:Cholesterol reduction with proprotein convertase subtilisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute coronary syndrome remains uncertain. OBJECTIVES: This study sought to determine whether further cholesterol reduction with alirocumab would be cost-effective in patients with a recent acute coronary syndrome on optimal statin therapy. METHODS: A cost-effectiveness model leveraging patient-level data from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was developed to estimate costs and outcomes over a lifetime horizon. Patients (n = 18,924) had a recent acute coronary syndrome and were on high-intensity or maximum-tolerated statin therapy, with a baseline low-density lipoprotein cholesterol (LDL-C) level ≥70 mg/dl, non-high-density lipoprotein cholesterol ≥100 mg/dl, or apolipoprotein B ≥80 mg/l. Alirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Alirocumab was blindly titrated to 150 mg if LDL-C remained ≥50 mg/dl or switched to placebo if 2 consecutive LDL-C levels were <15 mg/dl. Incremental cost per quality-adjusted life-year (QALY) was determined with the addition of alirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels ≥100 mg/dl and <100 mg/dl. RESULTS: Across the overall population recruited to the ODYSSEY OUTCOMES trial, using an annual treatment cost of US$5,850, the mean overall incremental cost-effectiveness ratio was US$92,200 per QALY (base case). The cost was US$41,800 per QALY in patients with baseline LDL-C ≥100 mg/dl, whereas in those with LDL-C <100 mg/dl the cost per QALY was US$299,400. Among patients with LDL-C ≥100 mg/dl, incremental cost-effectiveness ratios remained below US$100,000 per QALY across a wide variety of sensitivity analyses. CONCLUSIONS: In patients with a recent acute coronary syndrome on optimal statin therapy, alirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C ≥100 mg/dl but less economic value with LDL-C <100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402).
Authors: William S Weintraub; Deepak L Bhatt; Zugui Zhang; Sarahfaye Dolman; William E Boden; Adam P Bress; Jordan B King; Brandon K Bellows; Gabriel S Tajeu; Catherine G Derington; Jonathan Johnson; Katherine Andrade; P Gabriel Steg; Michael Miller; Eliot A Brinton; Terry A Jacobson; Jean-Claude Tardif; Christie M Ballantyne; Paul Kolm Journal: JAMA Netw Open Date: 2022-02-01