1. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
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Ridker, P. M., Revkin, J., Amarenco, P., Brunell, R., Civeira, F., Flather, M., Glynn, R. J., Gregoire, J., Jukema, J. W., Karpov, Y., Kastelein, J. J. P., Koenig, W., Lorenzatti, A., Manga, P., Masiukiewicz, U., Miller, M., Mosterd, A., Murin, J., Nicolau, J. C., Nissen, S., Ponikowski, P., Santos, R. D., Schwartz, P. F., Soran, H., White, H., Wright, R. S., Vrablik, M., Yunis, C., Shear, C. L., Tardif, Conde D, J. -C., Colquhoun, D, Missault, L, Grégoire, J, Gao, R, Urina, M, Solar, M, Jensen, Hk, Grobbee, D, Savolainen, M, Schiele, Fn, Montalescot, G, Edes, I, Blake, G, Lotan, C, Maggioni, A, Savonitto, S, Lee, Cw, Leiva Pons JL, Dan, Ga, Cortada, Jb, Mellbin, L, Kahan, T, Noble, S, Hwang, Jj, Sritara, P, Tökgozoğlu, L, Tarasenko, L, Borer, Js, Black, H, Carmena, R, Furie, Kl, Mcmurray, J, Neaton, J, Zannad, F, O’Neill, B, Welty, F, Mcnamara, R, Chun, H, Abbott, Jd, Jacoby, D, Mcpherson, C, Jadbabaie, F, Pinto, D, Mccullough, L, Silverman, Ie, Sansing, Lh, Dearborn-Tomazos, J, Foody, J, Schindler, J, Piazza, G, Chakrabarti, A, Pride, Y, Gelfand, E, Baultrukonis, D, Chaudhuri, S, Frederich, R, Johnson, M, Mridha, K, Powell, C, Wang, E, Wei, C, Anderson, P, Buonanno, M, Epsley, C, Evans, B, Frolova, M, Goetsch, M, Hessinger, D, Ikehara, E, Ivanac, K, Kizko, J, Le, K, McNally-Dufort, C, Morocco, T, Nadkarni, S, Nissen, T, Nye, R, Pak, R, Pence, D, Redifer, P, Schwartz, W, 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Gillespie, E, Bybee, Ka, Moriarty, Pm, Savin, V, Agaiby, Jm, Melucci, Mb, Jantzi, Cm, Davidson, E, Smith, Wb, Treasure, Cb, Wakefield, Ph, Deck, K, Edris, Ma, Gilmore, Rm, Seep, Mk, Andersen, Jl, Detweiler, Ro, Rosenfeld, Jc, Strobl, Dj, Steinhoff, Jp, Adams, A, Estevez, R, Molin, Cj, Kim, Cy, Dy, J, Fox, Ke, Farris, Nr, Wayne, Jd, Whitney, Rt, Randhawa, Pm, Mego, Dm, Macdolnald, L, Caputo, Rp, Rigolosi, R, Vannatta, B, Pacheco, Tr, El-Shahawy, M, Gonzalez, Ej, Guice, Mj, Cherlin, Rs, Bays, He, Shoukfeh, M, Morris, Fh, Loy, J, Vora, Sk, Staab, Pk, Frisoli, A, Kimmel, Ma, Cohen, Aj, Green, Cb, Whitlock, L, Butuk, Dj, Mccartney, Mj, Ables, Lr, Acosta, R, Alvarez, Jg, Barrera, Cm, Benitez, O, Berenguer, Ra, Breton, Cf, Chiong, R, Delgado, Mi, Dufreny, A, Fialkow, Ja, Franczek, S, Frias, Jj, Iglesias, C, Landron-Garcia, L, Llerena, Sn, Martinez, Rf, Miranda, Aa, Morytko, Ja, Rodriguez, Ij, Sotolongo, R, Suarez-Sarmiento, A, Terrelonge, Ae, Vaca, Ce, Venereo, Jm, Verdeza, C, Zeno, Ml, 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[Boston], Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), RS: CARIM - R3.02 - Hypertension and target organ damage, MUMC+: MA Alg Interne Geneeskunde (9), Interne Geneeskunde, Ridker, P. M., Glynn, R. J., Jukema, J. W., Kastelein, J. J. P., Nicolau, J. C., Santos, R. D., Schwartz, P. F., Wright, R. S., Shear, C. L., Tardif, J. -C., SPIRE Cardiovascular Outcome Investigator, Perrone, Filardi, P, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
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Male ,STATIN THERAPY ,Anticholesteremic Agents/adverse effects ,Antibodie ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Injections, Subcutaneous/adverse effects ,030204 cardiovascular system & hematology ,Bococizumab ,law.invention ,PCSK9 ,0302 clinical medicine ,Randomized controlled trial ,law ,Risk Factors ,GENETIC-VARIANTS ,Cardiovascular Disease ,Monoclonal ,Anticholesteremic Agent ,030212 general & internal medicine ,Myocardial infarction ,Treatment Failure ,Humanized ,Proprotein Convertase 9/antagonists & inhibitors ,Medicine(all) ,Antibodies ,Antibodies, Monoclonal, Humanized ,Anticholesteremic Agents ,Cardiovascular Diseases ,Cholesterol, LDL ,Double-Blind Method ,Female ,Follow-Up Studies ,Humans ,Hypercholesterolemia ,Injections, Subcutaneous ,Lipids ,Middle Aged ,Proprotein Convertase 9 ,Medicine (all) ,PCSK9 Inhibitors ,antibodies monoclonal humanized ,anticholesteremic agents ,cardiovascular diseases ,cholesterol, LDL ,double-blind method ,female ,follow-up studies ,humans ,hypercholesterolemia ,injections, subcutaneous ,lipids ,male ,middle aged ,proprotein convertase 9 ,risk factors ,treatment failure ,medicine (all) ,Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16] ,General Medicine ,Lipid ,3. Good health ,LDL/blood ,Multicenter Study ,Cholesterol ,TRIALS ,Cholesterol, LDL/blood ,Antibodies, Monoclonal, Humanized/adverse effects ,Randomized Controlled Trial ,subcutaneous ,lipids (amino acids, peptides, and proteins) ,Cardiovascular Diseases/prevention & control ,REDUCING LIPIDS ,Human ,medicine.medical_specialty ,animal structures ,Hypercholesterolemia/drug therapy ,Placebo ,Injections, Subcutaneou ,LDL ,Injections ,Follow-Up Studie ,EVENTS ,03 medical and health sciences ,Internal medicine ,medicine ,Journal Article ,Comparative Study ,METAANALYSIS ,Alirocumab ,business.industry ,Unstable angina ,Lipids/blood ,Risk Factor ,fungi ,Antibodies/blood ,ta3121 ,medicine.disease ,Surgery ,Evolocumab ,REDUCTION ,Humanized/adverse effects ,Subcutaneous/adverse effects ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Item does not contain fulltext BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P/=70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of >/=100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P
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- 2017
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