Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab: Pooled Data From Randomized Trials

Journal of the American College of Cardiology

Volumn 69, Issue 5, 2017, Pages 471-482

  Robinson, Jennifer G ^a   Rosenson, Robert S ^b   Farnier, Michel ^c   Chaudhari, Umesh ^d   Sasiela, William J ^e   Merlet, Laurence ^d   Miller, Kathryn ^f   Kastelein, John J P ^g  

^a UNIVERSITY OF IOWA   (United States)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^c Point Medical   (France)

^d SANOFI   (France)

^e REGENERON PHARMACEUTICALS INC   (United States)

^f REGENERON PHARMACEUTICALS INC   (United States)

^g ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

clinical trials; LDL C; PCSK9; safety

Indexed keywords

ALIROCUMAB; EZETIMIBE; HEMOGLOBIN A1C; HYDROCORTISONE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; RETINOL; SEX HORMONE; VITAMIN D; VITAMIN K GROUP; MONOCLONAL ANTIBODY;

ADULT; AMNESIA; APHASIA; ARTICLE; CATARACT; CONFUSION; CONTROLLED STUDY; DEMENTIA; DIABETES MELLITUS; DISORDERS OF HIGHER CEREBRAL FUNCTION; DRUG DOSE INCREASE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ESTIMATED GLOMERULAR FILTRATION RATE; EYE DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; FATTY LIVER; FEMALE; FRONTOTEMPORAL DEMENTIA; HEMOLYTIC ANEMIA; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTRANSAMINASEMIA; LIVER DISEASE; MAJOR CLINICAL STUDY; MALE; MUSCULOSKELETAL DISEASE; NEUROLOGIC DISEASE; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROPENSITY SCORE; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIDE EFFECT; BLOOD; FOLLOW UP; MIDDLE AGED; RANDOMIZED CONTROLLED TRIAL; SAFETY;

ANTIBODIES, MONOCLONAL; CHOLESTEROL, LDL; FEMALE; FOLLOW-UP STUDIES; HUMANS; HYPERCHOLESTEROLEMIA; MALE; MIDDLE AGED; PROPENSITY SCORE; SAFETY;

EID: 85011632539     PISSN: 07351097     EISSN: 15583597     Source Type: Journal    
DOI: 10.1016/j.jacc.2016.11.037     Document Type: Article

References (25)

1. 1 Boekholdt, S.M., Hovingh, G.K., Mora, S., et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol 64 (2014), 485–494.
2. 2 Wiviott, S.D., Cannon, C.P., Morrow, D.A., Ray, K.K., Pfeffer, M.A., Braunwald, E., 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 46 (2005), 1411–1416.
3. 3 Everett, B.M., Mora, S., Glynn, R.J., MacFadyen, J., Ridker, P.M., 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 114 (2014), 1682–1689.
4. 4 Cannon, C.P., Blazing, M.A., Giugliano, R.P., et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 372 (2015), 2387–2397.
5. 5 Robinson, J.G., Farnier, M., Krempf, M., et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 372 (2015), 1489–1499.
6. 6 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 169 (2015), 906–915.e13.
7. 7 Robinson, J.G., Nedergaard, B.S., Rogers, W.J., et al. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA 311 (2014), 1870–1882.
8. 8 Welty, F.K., Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol 25 (2014), 161–168.
9. 9 Goldstein, J.L., Brown, M.S., Atherosclerosis: the low-density lipoprotein receptor hypothesis. Metabolism 26 (1977), 1257–1275.
10. 10 Goldstein, J.L., Brown, M.S., The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 46 (1977), 897–930.
11. 11 Ginsberg, H.N., Rader, D.J., Raal, F.J., et al. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia and LDL-C of 160 mg/dl or higher. Cardiovasc Drugs Ther 30 (2016), 473–483.
12. 12 Cenedella, R.J., Cholesterol and cataracts. Surv Ophthalmol 40 (1996), 320–337.
13. 13 Ford, I., Murray, H., McCowan, C., Packard, C.J., Long-term safety and efficacy of lowering low-density lipoprotein cholesterol with statin therapy: 20-year follow-up of West of Scotland Coronary Prevention Study. Circulation 133 (2016), 1073–1080.
14. 14 Leuschen, J., Mortensen, E.M., Frei, C.R., Mansi, E.A., Panday, V., Mansi, I., Association of statin use with cataracts: a propensity score-matched analysis. JAMA Ophthalmol 131 (2013), 1427–1434.
15. 15 Yusuf, S., Bosch, J., Dagenais, G., et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 374 (2016), 2021–2031.
16. 16 Sabanayagam, C., Wang, J.J., Mitchell, P., et al. Metabolic syndrome components and age-related cataract: the Singapore Malay eye study. Invest Ophthalmol Vis Sci 52 (2011), 2397–2404.
17. 17 Schwartz, G.G., Bessac, L., Berdan, L.G., 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 (2014), 682–689.
18. 18 Lipinski, M.J., Benedetto, U., Escarcega, R.O., et al. The impact of proprotein convertase subtilisin-kexin type 9 serine protease inhibitors on lipid levels and outcomes in patients with primary hypercholesterolaemia: a network meta-analysis. Eur Heart J 37 (2016), 536–545.
19. 19 Sabatine, M.S., Giugliano, R.P., Wiviott, S.D., et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 372 (2015), 1500–1509.
20. 20 Martin, S.S., Blaha, M.J., Elshazly, M.B., et al. Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications. J Am Coll Cardiol 62 (2013), 732–739.
21. 21 Seidah, N.G., Awan, Z., Chretien, M., Mbikay, M., PCSK9: a key modulator of cardiovascular health. Circ Res 114 (2014), 1022–1036.
22. 22 Cariou, B., Ouguerram, K., Zair, Y., et al. PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol 29 (2009), 2191–2197.
23. 23 Zhao, Z., Tuakli-Wosornu, Y., Lagace, T., et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 79 (2006), 514–523.
24. 24 Hooper, A.J., Marais, A.D., Tanyanyiwa, D.M., Burnett, J.R., The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 193 (2007), 445–448.
25. 25 Thurnham, D.I., Davies, J.A., Crump, B.J., Situnayake, R.D., Davis, M., The use of different lipids to express serum tocopherol: lipid ratios for the measurement of vitamin E status. Ann Clin Biochem 23 (1986), 514–520.