Alirocumab for low-density lipoprotein cholesterol lowering

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References

• 1 The WHO: Top 10 causes of death (2018). www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
  Google Scholar
• 2 Ference BA, Ginsberg HN, Graham I et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 38, 2459–2472 (2017). •• Excellent review of atherosclerosis and its relationship to low-density lipoprotein cholesterol.
  Medline CASGoogle Scholar
• 3 Packard CJ. LDL cholesterol: how low to go? Trends Cardiovasc. Med. 28(5), 348–354 (2018).
  Medline CASGoogle Scholar
• 4 Brown MS, Goldstein JL. Lowering LDL – not only how low, but how long? Science 311(5768), 1721–1723 (2006).
  Medline CASGoogle Scholar
• 5 Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376, 1670–1681 (2010).
  MedlineGoogle Scholar
• 6 Schwartz GG, Steg PG, Szarek M et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N. Engl. J. Med. 379(22), 2097–2107 (2018).
  Medline CASGoogle Scholar
• 7 Kaplan H, Thompson RC, Trumble BC et al. Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet 389, 1730–1739 (2017).
  MedlineGoogle Scholar
• 8 Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. 376(18), 1713–1722 (2017). • Initial outcomes data for evolocumab.
  Medline CASGoogle Scholar
• 9 Roth EM. A safety evaluation of evolocumab. Expert Opin. Drug Saf. 17(1), 99–106 (2018).
  Medline CASGoogle Scholar
• 10 Cohen JC, Boerwinkle E, Mosley TH, Mosley TH, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354(12), 1264–1272 (2006). •• First clinical evidence that inhibiting PCSK9 may be of benefit in preventing cardiovascular disease.
  Medline CASGoogle Scholar
• 11 Praluent (alirocumab), prescribing information. Sanofi, NJ, USA (2018). http://products.sanofi.us/praluent/praluent.pdf
  Google Scholar
• 12 Djebli N, Martinez JM, Lohan L et al. Target-mediated drug disposition population pharmacokinetics model of alirocumab in healthy volunteers and patients: pooled analysis of randomized Phase I/II/III studies. Clin. Pharmacokinet. 56, 1155–1171 (2017).
  Medline CASGoogle Scholar
• 13 Roth EM, Diller P. Alirocumab for hyperlipidemia: physiology of PCSK9 inhibition, pharmacodynamics and Phase I and II clinical trial results of a PCSK9 monoclonal antibody. Future Cardiol. 10(2), 183–199 (2014).
  CASGoogle Scholar
• 14 Kastelein JJ, Hovingh GK, Langslet G et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J. Clin. Lipidol. 11(1), 195–203 (2017).
  MedlineGoogle Scholar
• 15 Defesche JC, Stefanutt C, Langslet G et al. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J. Clin. Lipidol. 11(6), 1338–1346 (2017).
  MedlineGoogle Scholar
• 16 Moriarty PM, Parhofer KG, Babirak SP et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur. Heart J. 37(48), 3588–3595 (2016). • Study showing ability to stop or decrease low-density lipoprotein apheresis in familial hypercholesterolemia patients.
  Medline CASGoogle Scholar
• 17 Robinson JG, Farnier M, Krempf M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372(16), 1489–1499 (2015).
  Medline CASGoogle Scholar
• 18 Kereiakes DJ, Robinson JG, Cannon CP et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am. Heart J. 169(6), 906–915 (2015).
  Medline CASGoogle Scholar
• 19 Cannon CP, Cariou B, Blom D et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur. Heart J. 36(19), 1186–1194 (2015).
  Medline CASGoogle Scholar
• 20 Bays H, Gaudet D, Weiss R et al. Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J. Clin. Endocrinol. Metab. 100(8), 3140–3148 (2015).
  Medline CASGoogle Scholar
• 21 Farnier M, Jones P, Severance R et al. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial. Atherosclerosis 244, 138–146 (2016).
  Medline CASGoogle Scholar
• 22 Koh KK, Nam CW, Chao TH et al. A randomized trial evaluating the efficacy and safety of alirocumab in South Korea and Taiwan (ODYSSEY KT). J. Clin. Lipidol. 12(1), 162–172 (2018).
  MedlineGoogle Scholar
• 23 Teramoto T, Kobayashi M, Tasaki H et al. Efficacy and safety of alirocumab in Japanese patients with heterozygous familial hypercholesterolemia or at high cardiovascular risk with hypercholesterolemia not adequately controlled with statins – ODYSSEY JAPAN randomized controlled trial. Circ. J. 80(9), 1980–1987 (2016).
  Medline CASGoogle Scholar
• 24 Moriarty PM, Thompson PD, Cannon CP et al. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial. J. Clin. Lipidol. 9(6), 758–769 (2015).
  MedlineGoogle Scholar
• 25 Leiter LA, Cariou B, Müller-Wieland D et al. Efficacy and safety of alirocumab in insulin-treated individuals with Type 1 or Type 2 diabetes and high cardiovascular risk: the ODYSSEY DM-INSULIN randomized trial. Diabetes Obes. Metab. 19(12), 1781–1792 (2017).
  Medline CASGoogle Scholar
• 26 Ray KK, Leiter LA, Müller-Wieland D et al. Alirocumab vs usual lipid-lowering care as add-on to statin therapy in individuals with Type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial. Diabetes Obes. Metab. 20(6), 1479–1489 (2018).
  Medline CASGoogle Scholar
• 27 Roth EM, McKenney JM. ODYSSEY MONO: effect of alirocumab 75 mg subcutaneously every 2 weeks as monotherapy versus ezetimibe over 24 weeks. Future Cardiol. 11(1), 27–37 (2015).
  CASGoogle Scholar
• 28 Roth EM, Moriarty PM, Bergeron J et al. A Phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I. Atherosclerosis 254, 254–262 (2016). •• Only study performed with 300 mg of alirocumab once monthly.
  Medline CASGoogle Scholar
• 29 Stroes E, Guyton JR, Lepor N et al. Efficacy and safety of alirocumab 150mg every 4 weeks in patients with hypercholesterolemia not on statin therapy: the ODYSSEY CHOICE II study. J. Am. Heart Assoc. 5(9), pii:e003421 (2016).
  Google Scholar
• 30 Kastelein JJ, Kereiakes DJ, Cannon CP et al. Effect of alirocumab dose increase on LDL lowering and lipid goal attainment in patients with dyslipidemia. Coron. Artery Dis. 28(3), 190–197 (2017).
  MedlineGoogle Scholar
• 31 Bays HE, Rosenson RS, Baccara-Dinet MT, Louie MJ, Thompson D, Hovingh GK. Assessment of the 1% of patients with consistent <15% reduction in low-density lipoprotein cholesterol: pooled analysis of 10 Phase III ODYSSEY alirocumab trials. Cardiovasc. Drugs Ther. 32(2), 175–180 (2018).
  Medline CASGoogle Scholar
• 32 Roth EM, Goldberg AC, Catapano AL et al. Antidrug antibodies in patients treated with alirocumab. N. Engl. J. Med. 376(16), 1589–1590 (2017). • Evidences that even in the presence of antidrug antibodies to alirocumab, there is no apparent clinical efficacy effect.
  MedlineGoogle Scholar
• 33 Catapano AL, Lee LV, Louie MJ, Thompson D, Bergeron J, Krempf M. Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase III clinical trials. Sci. Rep. 7, 45788 (2017).
  Medline CASGoogle Scholar
• 34 Ginsberg HN, Farnier M, Robinson JG et al. Efficacy and safety of alirocumab in individuals with diabetes mellitus: pooled analyses from five placebo-controlled Phase III studies. Diabetes Ther. 9(3), 1317–1334 (2018).
  Medline CASGoogle Scholar
• 35 Toth PP, Dwyer JP, Cannon CP et al. Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease. Kidney Int. 93(6), 1397–1408 (2018).
  Medline CASGoogle Scholar
• 36 McCullough PA, Ballantyne CM, Sanganalmath SK et al. Efficacy and safety of alirocumab in high-risk patients with clinical atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia (from 5 placebo-controlled ODYSSEY trials). Am. J. Cardiol. 121(8), 940–948 (2018).
  Medline CASGoogle Scholar
• 37 Leiter LA, Müuller-Wieland D, Baccara-Dinet MT, Letierce A, Samuel R, Cariou B. Efficacy and safety of alirocumab in people with prediabetes vs those with normoglycaemia at baseline: a pooled analysis of 10 Phase III ODYSSEY clinical trials. Diabet. Med. 35(1), 121–130 (2018).
  Medline CASGoogle Scholar
• 38 Kereiakes DJ, Lepor NE, Gerber R et al. Efficacy and safety of alirocumab in patients with or without prior coronary revascularization: pooled analysis of eight ODYSSEY Phase III trials. Atherosclerosis 277, 211–218 (2018).
  Medline CASGoogle Scholar
• 39 Harvey PD, Sabbagh MN, Harrison JE et al. No evidence of neurocognitive adverse events associated with alirocumab treatment in 3340 patients from 14 randomized Phase II and III controlled trials: a meta-analysis of individual patient data. Eur. Heart J. 39(5), 374–381 (2018).
  Medline CASGoogle Scholar
• 40 Giugliano RP, Mach F, Zavitz K et al. Cognitive function in a randomized trial of evolocumab. N. Engl. J. Med. 377(7), 633–643 (2017).
  Medline CASGoogle Scholar
• 41 Leiter LA, Muller-Wieland D, Baccara-Dinet MT, Letierce A, Samuel R, Cariou B. Efficacy and safety of alirocumab in people with prediabetes vs those with normoglycaemia at baseline: a pooled analysis of 10 Phase III ODYSSEY clinical trials. Diabet. Med. 35(1), 121–130 (2018).
  Medline CASGoogle Scholar
• 42 Schwartz GS, Bessac L, Berdan LG et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY Outcomes trial. Am. Heart J. 168(5), 682–689 (2014).
  Medline CASGoogle Scholar
• 43 Institute for Clinical and Economic Review. Alirocumab for high cholesterol – preliminary new evidence update (2018). https://icer-review.org/wp-content/uploads/2018/03/Alirocumab-Preliminary-New-Evidence-Update_03102018.pdf •• Favorable cost/benefit ratio for alirocumab with data from ODYSSEY OUTCOMES trial.
  Google Scholar
• 44 ACC Scientific Sessions presentation. FL, USA (2018). www.acc.org/education-and-meetings/image-and-slide-gallery/media-detail?id=90e30055844c402ba16d54fb05e45136
  Google Scholar