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

Volumn 244, Issue , 2016, Pages 138-146

  Farnier, Michel ^a   Jones, Peter ^b   Severance, Randall ^c   Averna, Maurizio ^d   Steinhagen Thiessen, Elisabeth ^e   Colhoun, Helen M ^f   Du, Yunling ^g   Hanotin, Corinne ^h   Donahue, Stephen ^g  

^a Point Medical   (France)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c RADIANT RESEARCH   (United States)

^d UNIVERSITY OF PALERMO   (Italy)

^e CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^f UNIVERSITY OF DUNDEE   (United Kingdom)

^g REGENERON PHARMACEUTICALS INC   (United States)

^h SANOFI   (France)

Author keywords

Alirocumab; Ezetimibe; Low density lipoprotein cholesterol; Monoclonal antibody; PCSK9; Rosuvastatin

Indexed keywords

ALIROCUMAB; EZETIMIBE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; ROSUVASTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPOCHOLESTEROLEMIC AGENT; MONOCLONAL ANTIBODY;

ADULT; ARTICLE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; HUMAN; LIPOPROTEIN BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; BLOOD; CARDIOVASCULAR DISEASES; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DOSE RESPONSE; DRUG EFFECTS; FOLLOW UP; HYPERCHOLESTEROLEMIA; MULTICENTER STUDY; RETROSPECTIVE STUDY; SUBCUTANEOUS DRUG ADMINISTRATION; TIME FACTOR; TREATMENT OUTCOME;

ANTIBODIES, MONOCLONAL; ANTICHOLESTEREMIC AGENTS; CARDIOVASCULAR DISEASES; CHOLESTEROL, LDL; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; EZETIMIBE; FOLLOW-UP STUDIES; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; INJECTIONS, SUBCUTANEOUS; RETROSPECTIVE STUDIES; ROSUVASTATIN CALCIUM; TIME FACTORS; TREATMENT OUTCOME;

EID: 84947976529     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2015.11.010     Document Type: Article

References (28)

1. Baigent C., Blackwell L., Emberson J., et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010, 376:1670-1681.
2. Stone N.J., Robinson J.G., Lichtenstein A.H., et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 2014, 129:S1-S45.
3. Cannon C.P., Blazing M.A., Giugliano R.P., et al. Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med. 2015, 372:2387-2397.
4. Anderson T.J., Gregoire J., Hegele R.A., et al. 2012 update of the Canadian cardiovascular society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can. J. Cardiol. 2013, 29:151-167.
5. Expert Dyslipidemia Panel of the International Atherosclerosis Society Panel members An international atherosclerosis society position paper: global recommendations for the management of dyslipidemia-full report. J. Clin. Lipidol. 2014, 8:29-60.
6. Perk J., De B.G., Gohlke H., et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur. Heart J. 2012, 33:1635-1701.
7. Reiner Z., Catapano A.L., De B.G., et al. ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur. Heart J. 2011, 32:1769-1818.
8. Stein E.A., Gipe D., Bergeron J., et al. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet 2012, 380:29-36.
9. Roth E.M., McKenney J.M., Hanotin C., et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N. Engl. J. Med. 2012, 367:1891-1900.
10. McKenney J.M., Koren M.J., Kereiakes D.J., et al. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J. Am. Coll. Cardiol. 2012, 59:2344-2353.
11. Roth E.M., Taskinen M.R., Ginsberg H.N., et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. Int. J. Cardiol. 2014, 176:55-61.
12. Cannon C.P., 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 ODYSSSEY COMBO II randomized controlled trial. Eur. Heart J. 2015, 36:1186-1194.
13. Robinson J.G., Farnier M., Krempf M., et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 2015, 372:1489-1499.
14. Kereiakes D.J., Robinson J.G., Cannon C.P., et al. Efficacy and safety of the PCSK9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am. Heart J. 2015, 169:906-915.e13.
15. Kastelein J.J.P., Ginsberg H.N., Langslet G., et al. Odyssey FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur. Heart J. 2015 Sep 1, pii:ehv370 (epub ahead of print).
16. Moriarty P.M., Thompson P.D., Cannon C.P., et al. Efficacy and safety of alirocumab versus ezetimibe in statin-intolerant patients, with a statin-re-challenge arm: the ODYSSEY ALTERNATIVE randomized trial. J. Clin. Lipidol. 2015, (epub ahead of print). 10.1016/j.jacl.2015.08.006.
17. Robinson J.G., Colhoun H.M., Bays H.E., et al. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS studies. Clin. Cardiol. 2014, 37:597-604.
18. Siddiqui O., Hung H.M., O'Neill R. MMRM vs. LOCF: a comprehensive comparison based on simulation study and 25 NDA datasets. J. Biopharm. Stat. 2009, 19:227-246.
19. National Research Council (US) Panel on Handling Missing Data in Clinical Trials The Prevention and Treatment of Missing Data in Clinical Trials 2010, National Academies Press (US), Washington (DC).
20. Jones P.H., Nair R., Thakker K.M. Prevalence of dyslipidemia and lipid goal attainment in statin-treated subjects from 3 data sources: a retrospective analysis. J. Am. Heart Assoc. 2012, 1:e001800.
21. Gitt A.K., Drexel H., Feely J., et al. Persistent lipid abnormalities in statin-treated patients and predictors of LDL-cholesterol goal achievement in clinical practice in Europe and Canada. Eur. J. Prev. Cardiol. 2012, 19:221-230.
22. Bays H.E., Davidson M.H., Massaad R., et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE study). Am. J. Cardiol. 2011, 108:523-530.
23. Jones P.H., Davidson M.H., Stein E.A., et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* trial). Am. J. Cardiol. 2003, 92:152-160.
24. Giugliano R.P., Desai N.R., Kohli P., et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 2012, 380:2007-2017.
25. Koren M.J., Scott R., Kim J.B., et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2012, 380:1995-2006.
26. Raal F., Scott R., Somaratne R., et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the reduction of LDL-C with PCSK9 inhibition in heterozygous familial hypercholesterolemia disorder (RUTHERFORD) randomized trial. Circulation 2012, 126:2408-2417.
27. Sullivan D., Olsson A.G., Scott R., et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 2012, 308:2497-2506.
28. Sanofi/Regeneron FDA Advisory Committee Briefing Document Praluent™ (Alirocumab) 2015, Available from:. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM449867.pdf.