Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab with Control

Circulation

Volumn 134, Issue 24, 2016, Pages 1931-1943

  Ray, Kausik K ^a   Ginsberg, Henry N ^b   Davidson, Michael H ^c   Pordy, Robert ^d   Bessac, Laurence ^e   Minini, Pascal ^e   Eckel, Robert H ^f   Cannon, Christopher P ^g  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b Columbia University ^*  (United States)

^c UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

^d REGENERON PHARMACEUTICALS INC   (United States)

^e SANOFI   (France)

^f UNIVERSITY OF COLORADO   (United States)

^g HARVARD CLINICAL RESEARCH INSTITUTE   (United States)

Author keywords

apolipoproteins; cardiovascular diseases; cholesterol, LDL; risk

Indexed keywords

ALIROCUMAB; APOLIPOPROTEIN B100; EZETIMIBE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIPID; LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; HYPOCHOLESTEROLEMIC AGENT; MONOCLONAL ANTIBODY;

ADULT; BRAIN ISCHEMIA; CARDIAC PATIENT; CARDIOVASCULAR DISEASE; COMPARATIVE STUDY; CONTROLLED STUDY; CORONARY ARTERY ATHEROSCLEROSIS; DOUBLE BLIND PROCEDURE; DRUG SAFETY; FAMILIAL HYPERCHOLESTEROLEMIA; FEMALE; FOLLOW UP; HEART INFARCTION; HIGH RISK PATIENT; HUMAN; ISCHEMIC HEART DISEASE; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; TREATMENT DURATION; UNSTABLE ANGINA PECTORIS; AGED; BLOOD; BODY MASS; CARDIOVASCULAR DISEASES; DOSE RESPONSE; DRUG ADMINISTRATION; PLACEBO EFFECT; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME;

AGED; ANTIBODIES, MONOCLONAL; ANTICHOLESTEREMIC AGENTS; APOLIPOPROTEIN B-100; BODY MASS INDEX; CARDIOVASCULAR DISEASES; CHOLESTEROL, LDL; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; EZETIMIBE; FEMALE; FOLLOW-UP STUDIES; HUMANS; LIPIDS; MALE; MIDDLE AGED; PLACEBO EFFECT; PROSPECTIVE STUDIES; TREATMENT OUTCOME;

EID: 84994682639     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.116.024604     Document Type: Review

References (34)

1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497. doi: 10.1001/jama.285.19.2486
2. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227-239. doi: 10.1161/01.CIR.0000133317.49796.0E.
3. Wood D. JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart. 2005;91:v1-v52.
4. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D. 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.
5. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 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. J Am Coll Cardiol. 2014;63(pt B):2889-2934. doi: 10.1016/j.jacc.2013.11.002.
6. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVEIT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-2397. doi: 10.1056/NEJMoa1410489.
7. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495-1504. doi: 10.1056/NEJMoa040583.
8. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425-1435. doi: 10.1056/NEJMoa050461.
9. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-2207. doi: 10.1056/NEJMoa0807646.
10. Cannon CP, Cariou B, Blom D, McKenney JM, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM; ODYSSEY COMBO II Investigators. 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. 2015;36:1186-1194. doi: 10.1093/eurheartj/ehv028.
11. Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM. 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. 2015;169:906-915. e13. doi: 10.1016/j.ahj.2015.03.004.
12. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ; ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489-1499. doi: 10.1056/NEJMoa1501031.
13. National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. NICE guidelines. https://www.nice.org.uk/guidance/cg181. March 31, 2016.
14. Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr, DePalma SM, Minissian MB, Orringer CE, Smith SC Jr. 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2016;68:92-125.
15. 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. doi: 10.1016/j.jacl.2013.12.005
16. Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, McKenney JM, Grundy SM, Gill EA, Wild RA, Wilson DP, Brown WV. National lipid association recommendations for patient-centered management of dyslipidemia, part 1: full report. J Clin Lipidol. 2015;9:129-169. doi: 10.1016/j.jacl.2015.02.003.
17. Bays H, Gaudet D, Weiss R, Ruiz JL, Watts GF, Gouni-Berthold I, Robinson J, Zhao J, Hanotin C, Donahue S. Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metab. 2015;100:3140-3148. doi: 10.1210/jc.2015-1520.
18. Farnier M, Jones P, Severance R, Averna M, Steinhagen-Thiessen E, Colhoun HM, Du Y, Hanotin C, Donahue S. 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. 2016;244:138-146. doi: 10.1016/j.atherosclerosis. 2015.11.010.
19. Ginsberg HN, Rader DJ, Raal FJ, Guyton JR, Baccara-Dinet MT, Lorenzato C, Pordy R, Stroes E. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia and LDLC of 160 mg/dl or higher. Cardiovasc Drugs Ther. 2016;30:473-483. doi: 10.1007/s10557-016-6685-y.
20. Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R, Blom D, Civeira F, Krempf M, Lorenzato C, Zhao J, Pordy R, Baccara-Dinet MT, Gipe DA, Geiger MJ, Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015;36:2996-3003. doi: 10.1093/eurheartj/ehv370.
21. Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, Bruckert E, Jacobson TA, Kopecky SL, Baccara-Dinet MT, Du Y, Pordy R, Gipe DA; ODYSSEY ALTERNATIVE Investigators. Efficacy and safety of alirocumab vs ezetimibe in statinintolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol. 2015;9:758-769. doi: 10.1016/j.jacl.2015.08.006.
22. Roth EM, Taskinen MR, Ginsberg HN, Kastelein JJ, Colhoun HM, Robinson JG, Merlet L, Pordy R, Baccara-Dinet MT. 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. doi: 10.1016/j.ijcard.2014.06.049.
23. Schwartz GG, Bessac L, Berdan LG, Bhatt DL, Bittner V, Diaz R, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Mahaffey KW, Moryusef A, Pordy R, Roe MT, Rorick T, Sasiela WJ, Shirodaria C, Szarek M, Tamby JF, Tricoci P, White H, Zeiher A, Steg PG. 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. 2014;168:682-689. doi: 10.1016/j.ahj.2014.07.028.
24. Wiviott SD, Cannon CP, Morrow DA, Ray KK, Pfeffer MA, Braunwald E; PROVE IT-TIMI 22 Investigators. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46:1411-1416. doi: 10.1016/j. jacc.2005.04.064.
25. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. 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.
26. Mindell J, Aresu M, Zaninotto P, Falaschetti E, Poulter N. Improving lipid profiles and increasing use of lipid-lowering therapy in England: results from a national cross-sectional survey-2006. Clin Endocrinol (Oxf). 2011;75:621-627. doi: 10.1111/j.1365-2265.2011.04094.x.
27. Kuklina EV, Yoon PW, Keenan NL. Trends in high levels of lowdensity lipoprotein cholesterol in the United States, 1999-2006. JAMA. 2009;302:2104-2110. doi: 10.1001/jama.2009.1672.
28. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993-2000.
29. Boekholdt SM, Hovingh GK, Mora S, Arsenault BJ, Amarenco P, Pedersen TR, LaRosa JC, Waters DD, DeMicco DA, Simes RJ, Keech AC, Colquhoun D, Hitman GA, Betteridge DJ, Clearfield MB, Downs JR, Colhoun HM, Gotto AM Jr, Ridker PM, Grundy SM, Kastelein JJ. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64:485-494. doi: 10.1016/j. jacc.2014.02.615.
30. Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ, Simes RJ, Durrington P, Hitman GA, Welch KM, DeMicco DA, Zwinderman AH, Clearfield MB, Downs JR, Tonkin AM, Colhoun HM, Gotto AM Jr, Ridker PM, Kastelein JJ. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307:1302-1309. doi: 10.1001/jama.2012.366.
31. Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A metaregression analysis. J Am Coll Cardiol. 2005;46:1855-1862. doi: 10.1016/j.jacc.2005.05.085.
32. Robinson JG, Wang S, Smith BJ, Jacobson TA. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol. 2009;53:316-322. doi: 10.1016/j.jacc.2008.10.024.
33. LaRosa JC, Grundy SM, Kastelein JJ, Kostis JB, Greten H; Treating to New Targets (TNT) Steering Committee and Investigators. Safety and efficacy of atorvastatin-induced very low-density lipoprotein cholesterol levels in patients with coronary heart disease (a post hoc analysis of the Treating to New Targets [TNT] study). Am J Cardiol. 2007;100:747-752. doi: 10.1016/j.amjcard. 2007.03.102.
34. Everett BM, Mora S, Glynn RJ, MacFadyen J, Ridker PM. Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (<30 mg/dl) with rosuvastatin 20 mg daily (from JUPITER). Am J Cardiol. 2014;114:1682-1689. doi: 10.1016/j. amjcard.2014.08.041.