@article{b0a60bc08d9b4a1eb0e4452955751b43,
title = "Cardiovascular efficacy and safety of bococizumab in high-risk patients",
abstract = "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<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥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<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients.",
keywords = "Lipids, Coronary disease, Myocardial infarction, Prevention, Bococizumab",
author = "Ridker, {P. M.} and J. Revkin and P. Amarenco and R. Brunell and M. Curto and F. Civeira and M. Flather and Glynn, {R. J.} and J. Gregoire and Jukema, {J. W.} and Y. Karpov and Kastelein, {J. J.P.} and W. Koenig and A. Lorenzatti and P. Manga and U. Masiukiewicz and M. Miller and A. Mosterd and J. Murin and Nicolau, {J. C.} and S. Nissen and P. Ponikowski and Santos, {R. D.} and Schwartz, {P. F.} and H. Soran and H. White and Wright, {R. S.} and M. Vrablik and C. Yunis and Shear, {C. L.} and Tardif, {J. C.} and {SPIRE Cardiovascular Outcome Investigators} and D. Conde and D. Colquhoun and Missault, {L. H.} and R. Gao and M. Urina and M. Solar and Jensen, {H. K.} and D. Grobbee and M. Savolainen and Schiele, {F. N.} and G. Montalescot and I. Edes and G. Blake and C. Lotan and A. Maggioni and S. Savonitto and Lee, {C. W.} and {Leiva Pons}, {J. L.} and Dan, {G. A.} and Cortada, {J. B.} and L. Mellbin and T. Kahan and Stephane Noble and Hwang, {J. J.} and P. Sritara and L. T{\"o}kgozoğlu and L. Tarasenko and Borer, {J. S.} and H. Black and R. Carmena and Furie, {K. L.} and J. McMurray and J. Neaton and F. Zannad and Blair O'Neill and F. Welty and Robert McNamara and H. Chun and Abbott, {J. D.} and Daniel Jacoby and Craig McPherson and F. Jadbabaie and Duane Pinto and L. McCullough and Silverman, {I. E.} and Sansing, {L. H.} and J. Dearborn-Tomazos and J. Foody and J. Schindler and G. Piazza and A. Chakrabarti and Y. Pride and E. Gelfand and D. Baultrukonis and S. Chaudhuri and R. Frederich and M. Johnson and K. Mridha and Coralie Powell and Ellen Wang and C. Wei and P. Anderson and M. Buonanno and C. Epsley and B. Evans and M. Frolova and M. Goetsch and D. Hessinger and E. Ikehara and K. Ivanac and J. Kizko and Kim Le and C. McNally-Dufort and T. Morocco and S. Nadkarni and Thor Nissen and R. Nye and R. Pak and D. Pence and P. Redifer and Whitney Schwartz and C. Sattler and R. Schade and B. Sullivan and J. Wegner and Alvarez, {C. A.} and N. Budassi and Vogel, {D. R.} and H. Avaca and Estol, {C. C.} and E. Gelersztein and Glenny, {J. A.} and Hershson, {A. R.} and Bruno, {R. L.} and Maffei, {L. E.} and Soler, {J. M.} and Zaidman, {C. J.} and Carnero, {G. S.} and Colombo, {H. R.} and Jure, {H. O.} and Luquez, {H. A.} and Ramos, {H. R.} and Resk, {J. H.} and Rusculleda, {M. M.} and Ulla, {M. R.} and A. Caccavo and Farias, {E. F.} and Wenetz, {L. M.} and Cabella, {P. R.} and Cuadrado, {J. A.} and M. Chahin and Mackinnon, {I. J.} and Zarandon, {R. B.} and J. Schmidberg and Fernandez, {A. A.} and O. Montana and Codutti, {O. R.} and Gorosito, {V. M.} and N. Maldonado and J. Sala and {De La Fuente}, {R. A.} and Casabella, {T. E.} and {Di Gennaro}, {J. P.} and Guerrero, {R. A.} and Alvarez, {M. S.} and M. Berli and Botta, {C. E.} and Montenegro, {E. E.} and Vico, {M. L.} and A. Begg and R. Lehman and Gilfillan, {C. P.} and M. d'Emden and Markovic, {T. P.} and D. Sullivan and C. Aroney and Stranks, {S. N.} and Crimmins, {D. S.} and M. Arstall and {Van Gaal}, W. and T. Davis and Aylward, {P. E.} and J. Amerena and M. William and J. Proietto and Purnell, {P. W.} and B. Singh and Arya, {K. W.} and Dart, {A. M.} and P. Thompson and Davis, {S. M.} and Carroll, {P. A.} and {De Looze}, F. and R. Jayasinghe and R. Bhindi and I. Buysschaert and T. Sarens and {van de Borne}, P. and Scott, {B. P.} and J. Roosen and F. Cools and C. Debroye and Schoors, {D. F.} and G. Hollanders and Schroe, {H. H.} and {De Sutter}, J. and K. Hermans and M. Carlier and {van Landegem}, P. and J. Verwerft and T. Mulleners and Delforge, {M. D.} and V. Soufflet and I. Elegeert and Descamps, {O. S.} and S. Janssens and Lemmens, {R. C.} and P. Desfontaines and A. Scheen and S. Heijmans and L. Capiau and G. Vervoort and Carlier, {S. G.} and D. Faes and B. Alzand and S. Keuleers and {De Wolf}, L. and J. Thoeng and {De Bruyne}, L. and {de Santos}, {M. O.} and Felicio, {J. S.} and Areas, {C. A.} and Figueiredo, {E. L.} and Michalaros, {Y. L.} and Neuenschwander, {F. C.} and G. Reis and Saad, {J. A.} and Kormann, {A. P.} and Nascimento, {C. V.} and Precoma, {D. B.} and E. Abib and {dos Santos}, {F. R.} and Mello, {Y. G.} and Saraiva, {J. F.} and Rech, {R. L.} and R. Cerci and Fortes, {J. A.} and Rossi, {P. R.} and {de Lima e Silva}, {F. A.} and M. Hissa and Silva, {R. P.} and {de Souza}, {W. K.} and {Guimar{\~a}es Filho}, {F. V.} and Mangili, {O. C.} and {de Oliveira Paiva}, {M. S.} and R. Tumelero and Abrantes, {J. A.} and Caramori, {P. R.}",
year = "2017",
month = apr,
day = "20",
doi = "10.1056/NEJMoa1701488",
language = "English",
volume = "376",
pages = "1527--1539",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "16",
}