Ridker, P. M., Revkin, J., Amarenco, P., Brunell, R., Curto, M., 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., ... Vincent, J. (2017). Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients. New England Journal of Medicine, 376(16), 1527-1539. https://doi.org/10.1056/NEJMoa1701488

@article{cc71d6f7a9e94a7b82bd96e58d7f15d5,
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 = "Statin therapy, GENETIC-VARIANTS, REDUCING LIPIDS",
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 Diego Conde and David Colquhoun and Luc Missault and Jean Gregoire and Runlin Gao and Miguel Urina and Miroslav Solar and Jensen, {Henrik Kjaerulf} and Diederick Grobbee and Markku Savolainen and Francois Schiele and Gilles Montalescot and Istvan Edes and Gavin Blake and Chaim Lotan and Aldo Maggioni and Stefano Savonitto and Lee, {Cheol Whan} and {Leiva Pons}, {Jose Luis} and Gheorghe-Andrei Dan and {Bruguera Cortada}, Jordi and Linda Mellbin and Thomas Kahan and Stephane Noble and Juey-Jen Hwang and Piyamitr Sritara and Lale Tokgozoglu and Jim Revkin and Lisa Tarasenko and Borer, {Jeffrey S.} and Henry Black and Rafael Carmena and Furie, {Karen L.} and John McMurray and James Neaton and Faiez Zannad and Blair O'Neill and Francine Welty and Robert McNamara and Hyung Chun and Abbott, {J. Dawn} and Daniel Jacoby and Craig McPherson and Farid Jadbabaie and Duane Pinto and Louise McCullough and Silverman, {Isaac E.} and Sansing, {Lauren H.} and Jennifer Dearborn-Tomazos and Joanne Foody and Joseph Schindler and Gregory Piazza and Anjan Chakrabarti and Yuri Pride and Eli Gelfand and Dan Baultrukonis and Sandip Chaudhuri and Robert Frederich and Margot Johnson and Khurshid Mridha and Coralie Powell and Ellen Wang and Caimiao Wei and Patricia Anderson and Marjorie Buonanno and Charlotte Epsley and Barbara Evans and Martina Frolova and Martina Goetsch and Diane Hessinger and Edson Ikehara and Karen Ivanac and Jan Kizko and Kim Le and Christine McNally-Dufort and Tamara Morocco and Sharayu Nadkarni and Thor Nissen and Regina Nye and Raphael Pak and Debbie Pence and Patricia Redifer and Whitney Schwartz and Catherine Sattler and Robin Schade and Beth Sullivan and John Wegner and Alvarez, {C. A.} and N. Budassi and Vogel, {D. R.} and H. Avaca and Conde, {D. G.} and Estol, {C. C. C. J.} and E. Gelersztein and Glenny, {J. A.} and Hershson, {A. R.} and Bruno, {R. L.} and Maffei, {L. E.} and Soler, {J. M. P.} 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. M.} and Cabella, {P. R. F.} and Cuadrado, {J. A.} and M. Chahin and Mackinnon, {I. J.} and Zarandon, {R. B. S.} 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. L.} and Casabella, {T. E. S.} and {Di Gennaro}, {J. P. A.} and Guerrero, {R. A. 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 D. Colquhoun 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 Missault, {L. H.} 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. N.} and Felicio, {J. S.} and Areas, {C. A. F.} and Figueiredo, {E. L.} and Michalaros, {Y. L.} and Neuenschwander, {F. C.} and G. Reis and Saad, {J. A.} and Kormann, {A. P. M.} and Nascimento, {C. V.} and Precoma, {D. B.} and Abib, {E., Jr.} and {dos Santos}, {F. R.} and Mello, {Y. G.} and Saraiva, {J. F. K.} and Rech, {R. L.} and R. Cerci and Fortes, {J. A. R.} and Rossi, {P. R. F.} and {de Lima e Silva}, {F. A.} and M. Hissa and Silva, {R. P.} and {de Souza}, {W. K. S. B.} and Filho, {F. V. Guimaraes} and Mangili, {O. C.} and {de Oliveira Paiva}, {M. S. M.} and R. Tumelero and Abrantes, {J. A. M.} and Caramori, {P. R.} and Dutra, {O. P.} and Leaes, {P. E.} and Manenti, {E. R.} and Polanczyk, {C. A.} and Farias, {F. A. Bandeira e} and {de Moraes}, {J. B. X. Junior} and Russo, {L. A.} and Alves, {A. R., Jr.} and Dracoulakis, {M. D. A.} and Ritt, {L. E. F.} and Saporito, {W. F.} and Herdy, {A. H.} and Maia, {L. N.} and Sternieri, {M. V. B. B.} and Ayoub, {J. C. A.} and Bianco, {H. T.} and {da Costa}, {F. A.} and Eliaschewitz, {F. G.} and Fonseca, {F. A. H.} and Nakandakare, {E. R.} and Bonansea, {T. C. P.} and Castro, {N. M. S.} and {de Barros e Silva}, {P. G. M.} and P. Smith and Botelho, {R. V.} and Resende, {E. S.} and Barbieri, {D. S. G.} and Hernandes, {M. E.} and H. Bajaj and P. Beaudry and Berlingieri, {J. C.} and Salter, {T. J.} and B. Ajala and Anderson, {T. J.} and A. Nanji and D. Desrosiers and D. Gaudet and G. Moran and Csanadi, {M. A.} and E. StAmour and S. Cusimano and Halperin, {F. A.} and M. Babapulle and S. Vizel and J. Petrella and Spence, {J. D.} and N. Gupta and G. Tellier and R. Bourgeois and J. Gregoire and T. Wesson and R. Zadra and Twum-Barima, {D. Y.} and Cha, {J. Y.} and Hartleib, {M. C.} and J. Bergeron and G. Chouinard and McPherson, {T. P.} and G. Searles and Peterson, {S. R.} and A. Mukherjee and S. Lepage and Conway, {J. R.} and Kouz, {S. M.} and D. Dion and Y. Pesant and Cheung, {S. S.} and Goldenberg, {R. M.} and R. Aronson and Gupta, {A. K.} and M. O'Mahoney and L. Pliamm and I. Teitelbaum and Hoag, {G. N.} and Nadra, {I. J.} and Z. Yared and Yao, {L. C.} and T. Nguyen and Saunders, {K. K.} and Y. Li and D. Wang and J. Li and X. Yang and Y. Du and G. Wang and P. Yang and X. Zhang and P. Xu and Y. Zhao and Chen, {J. C.} and S. Li and W. Li and L. Zhang and Y. Zhu and Y. Zhang and C. Zhou and Y. Wang and F. Liu and Y. Ma and Z. Ti and X. Zeng and Y. Zhou and G. Cui and D. Li and L. Xue and J. Jiang and Y. Lian and Y. He and Mendoza, {J. A.} and Bonfanti, {J. A. C.} and Dada, {F. A. T.} and Urina-Triana, {M. A.} and Rodriguez, {W. R. B.} and Sanchez, {M. L. J.} and Lozno, {H. Y.} and Triana, {E. H.} and Arambula, {R. M. S.} and Rico-Carrillo, {A. E.} and Gallo, {H. J. H.} and Catano, {J. S. V.} and Jattin, {F. G. M.} and Plazas, {J. A. R.} and Gomez, {J. E. F.} and R. Botero-Lopez and Gomez, {N. I. J.} and Munoz, {C. F. J.} and Pelaez, {S. V.} and Eraso, {A. M.} and Goyes, {A. R. B.} and L. Elbl and N. Fiserova and J. Vesely and B. Wasserburger and V. Blaha and J. Vojacek and P. Maskova and M. Hutyra and J. Vrkoc and T. Hala and P. Vodnansky and P. Bocek and R. Cifkova and V. Bufka and R. Ceska and M. Machkova and E. Zidkova and M. Lukac and T. Mikusova and I. Kellnerova and L. Kuchar and R. Ferkl and V. Cech and S. Zemek and Z. Monhart and F. Davidsen and A. Joensen and Lihn, {A. S.} and Rasmussen, {T. K.} and H. Wiggers and Lindgren, {L. M.} and U. Schmidt and S. Galatius and H. Sillesen and Schou, {J. Bronnum} and Thomsen, {K. K.} and S. Urhammer and J. Jeppensen and M. Schou and O. May and R. Steffensen and Nielsen, {W. B.} and T. Nielesen and Jepsen, {J. M.} and A. Rai and R. Sykulski and H. Rickers and L. Frost and Js Lomholdt and K. Egstrup and S. Wermuth and C. Klausen and J. Lassus and A. Palomaki and J. Khari and T. Tatlisumak and S. Kekki and E. Vanttinen and A. Strandberg and M. Valtonen and Sia, {S. M.} and O. Nerg and M. Puhakka and M. Savolainen and J. Strand and M. Timonen and J. Levola and L. Arstila and J. Taurio and I. Kantola and J. Suomi and K. Humaloja and K. Askonen and F. Schiele and I. Sibon and G. Zemour and P. Goube and C. Petit and Z. Chati and G. Range and F. Rabahi and R. Rihani and C. Bergerot and F. Roubille and A. Boye and V. Probst and E. Ferrari and G. Cayla and E. Thouvenot and N. Delarche and T. Couffinhal and D. Coisne and F. Paillard and M. Elbaz and E. Decoulx and D. Angoulvant and B. Agraou and S. Caudmont and J. Berrouschot and B. Lauer and I. Schoell and D. Trenk and K-M Derwahl and A. Khariouzov and F. Proepper and P. Stawowy and Stephan, {U. Da} and J. Stoessel and H-F Voehringer and T. Dorsel and C. Stellbrink and A. Rinke and J. Northroff and H. Bourhaial and M. Stratmann and T. Wetzel and C. Axthelm and A. Guenzel and I. Weigmann and M. Faghih and D. Hagemann and A. Schaefer and D. Weber and J. Luedemann and C. Contzen and Kornmann, {M. O.} and B. Winkelmann and J. Simon and S. Felix and C. Brauer and U. Laufs and E. Schmidt and I. Marten and M. Licka and J. Heisters and Appel, {K. F.} and U. Kleinecke-Pohl and C. Klein and {von Hodenberg}, {E. F.} and O. Maus and H. Sigal and H. Taeschner and P. Schwimmbeck and B. Lemke and C. Perings and G. Illies and A. Pfuetzner and P. Salbach and C. Hengstenberg and A. Kohler and H. Mudra and T. Behnke and M. Baar and M. Jeserich and G. Scholz and I. Naudts and H. Voller and H-J Herrmann and {von Engelhardt}, {C. B.} and S. Gerke and L. Pohlmeier and T. Schaufele and J. Woehrle and A. Al-Zoebi and T. Horacek and E. Peterfai and V. Kemeny and F. Lakatos and E. Bod and P. Andrassy and P. Andreka and T. Balo and Z. Davidovits and Z. Laszlo and K. Nagy and A. Papp and A. Somogyi and E. Toldy-Schedel and A. Vertes and P. Voros and G. Paragh and T. Martyin and C. Hajdu and L. Deak and K. Farago and A. Nagy and R. Kirschner and Z. Koszegi and Z. Zilahi and K. Toth and I. Wittmann and D. Bajcsi and I. Reiber and L. Toth and B. Benczur and L. Nagy and T. Sydo and G. Lupkovics and T. Oroszlan and P. Crean and Mahon, {N. G.} and B. McAdam and B. MacNeill and A. Katz and D. Tsalihin and A. Vazan and A. Eitan and Lewis, {B. S.} and D. Gavish and J. Wainstein and O. Mosenzon and M. Mosseri and V. Vishlitzky and S. Atar and Nseir, {W. B.} and H. Brenner and A. Elis and S. Fuchs and I. Shimon and A. Solodky and A. Goldhaber and D. Tanne and H. Knobler and Kracoff, {O. H.} and O. Hussein and E. Auriel and E. Chorin and T. Sharir and R. Bitzur and M. Shechter and R. Antonicelli and E. Franceschini and M. Porcu and G. Sesti and S. Maggiolini and A. Salvioni and Filardi, {P. P.} and B. Trimarco and M. Averna and L. Pasqualini and M. Pirro and M. Pantaleoni and G. Piovaccari and M. Arca and F. Fedele and L. Roncon and M. Anselmi and P. Sganzerla and G. Morocutti and E. Bonora and Dimas, {A. L.} and Esperon, {G. A. L.} and E. Morales-Villegas and Isunza, {J. M. R.} and Beltran, {L. G. M.} and Molina, {C. A. A.} and Garcia, {D. K.} and Ruiz, {L. A. N.} and Reyna, {L. S.} and {De los Rios Ibarra}, {M. O.} and Soto, {J. R. L.} and M. Gonzalez-Ortiz and M. Herrera-Marmolejo and Ramos, {S. A. J.} and Ramos-Lopez, {G. A.} and Stobschinski, {C. A.} and AguilarSalinas, {C. A.} and M. Alpizar-Salazar and M. Jimenez-Sanchez and {Sanchez Mijangos}, {J. H.} and {Elizondo Moreno}, {E. R.} and {Garcia Castillo}, A. and {Garcia Hernandez}, {P. A.} and Gonzalez-Gonzalez, {J. G.} and {Riojas Charles}, {C. M.} and {Valdez Lopez}, {H. G.} and {Nuriulu Escobar}, {P. L.} and {Lechuga Martin del Campo}, A. and {Castro Montes}, {B. E.} and {Mendez Bucio}, A. and I. Rodriguez-Briones and {Torre Amione}, G. and {Violante Ortiz}, R. and {Luna Ceballos}, {R. I.} and {Lopez Rosas}, E. and Bax, {W. A.} and M. Alhakim and {van de Wiel}, A. and S-S Liem and Groutars, {R. G. E. J.} and Herrman, {J-P R.} and Hovingh, {G. K.} and {van de Wetering}, {M. L.} and {van Royen}, N. and Groenemeijer, {B. E.} and G. Hoedemaker and J. Schaap and E. Ronner and M. Angun and Mairuhu, {A. T.} and {Van Alem}, {A. P.} and Martens, {F. M. A. C.} and Heijmeriks, {J. A.} and {van Hal}, {J. M. C.} and Schoofs, {M. W.} and {den Hartog}, {F. R.} and S. Kentgens and Post, {J. C.} and Louwerenburg, {J. W.} and {van Rossum}, P. and Viergever, {E. P.} and Donders, {S. H.} and Kamphuisen, {P. W.} and {van Beek}, E. and R. Nijmeijer and T. Lenderink and T. Schreuder and Kuijper, {A. F.} and The, {S. H.} and Hof-Wiersma, {J. J. Van Het} and P. Tichelaar and I. Westerndorp and Breedveld, {R. W.} and Romer, {T. J.} and K. Bogaard and {Van Koningsbruggen}, P. and Kroon, {A. A.} and Hoogslag, {P. A.} and Rensing, {B. J.} and E. Cramer and Remmen, {J. J.} and Riksen, {N. P.} and Bokern, {M. J.} and Cabezas, {M. C.} and H. Mulder and Nierop, {P. R.} and {van Kempen}, {W. W.} and Zoet-Nugteren, {S. K.} and {van Daele}, {M. E.} and Swart, {H. P.} and {van der Zwaan}, {C. T.} and Hermans, {W. R.} and M. Magro and {van de Wal}, {R. M. A.} and Hassink, {R. J.} and Visseren, {F. L.} and A. Veenendaal and {De Nooijer}, C. and Troquay, {R. P.} and Imholz, {B. P.} and {van der Meer}, P. and Visser, {Rieuwk P.} and {van Leendert}, {R. J.} and Gosselink, {M. A.} and J. Baker and Benatar, {J. R.} and J. Kerr and Pryke, {J. R.} and Scott, {R. S.} and Millar-Corte, {G. D.} and M. Williams and B. Montgomery and Venter, {D. J.} and Ternouth, {I. F.} and DeCaigney, {S. C.} and Hart, {H. H.} and A. Corin and Garden, {P. I.} and D. Sheahan and Harding, {Sc A.} and J. Korecki and J. Supronik and M. Styczkiewicz and R. Bijata-Bronisz and T. Rusicka and M. Walczak and Z. Krolikowski and J. Ostrowski and M. Lukaszewicz and M. Przekwas-Jaruchowska and B. Zieba and P. Miekus and A. Orkwiszewska-Nalewajko and M. Piepiorka and P. Kubalski and K. Wychota and E. Blach and A. Ochala and B. Okopien and D. Wronska and M. Janion and D. Czarnecka and J. Kolodziejczyk and M. Konieczynska and K. Landa and E. Mirek-Bryniarska and M. Necki and Pasternak, {D. A.} and P. Rozpondek and J. Trebacz and J. Walczewska and M. Sidor and M. Broncel and J. Drozdz and M. Kosmider and M. SaryuszWolska and D. Kucharska and E. Opalinska and Z. Pijanowski and I. Wozniak and K. Banaszkiewicz and A. Klecha and M. Horodecki and J. Piskorz-Wapinska and I. Kobielusz-Gembala and Kim, {M. H.} and D-K Kim and Cho, {B. R.} and K-S Kim and S-H Her and Lee, {S. Y.} and Rhee, {M. Y.} and K. Kim and W-C Kang and Kim, {D. H.} and Y-S Cho and Kim, {S. H.} and Lee, {C. W.} and Rim, {S. J.} and S-J Tahk and Jeon, {H. K.} and J. Yoon and M. Mociran and Pop, {C. F.} and B. Minescu and Andrei, {L. D.} and M. Radoi and A. Calin and Ciomag, {R. M.} and I. Copaci and Dan, {G. A.} and A-G Fruntelata and M. Popescu and S. Tivadar and G. Roman and Avram, {R. I.} and Mistodie, {C. V.} and M. Morosanu and Popa, {A. R.} and Popescu, {M. L.} and Popoviciu, {M. S.} and A. Tase and M. Busegeanu and A. Popescu and I. Szilagyi and Sitterli-Natea, {C. N.} and Maximov, {D. M.} and M. Munteanu and Negrisanu, {G. D.} and A. Kuzin and D. Popov and J. Shapovalova and E. Vishneva and E. Shutemova and E. Pasechnik and E. Bogdanov and N. Khasanov and Barbarash, {O. L.} and Shangina, {O. A.} and N. Tarasov and O. Solonev and E. Kosmacheva and Chernyatina, {M. A.} and M. Ginzburg and A. Blokhin and N. Bulanova and Drapkina, {O. M.} and Gordeev, {I. G.} and Libov, {I. A.} and N. Lomakin and E. Panchenko and Shogenov, {Z. S.} and D. Zateyshchikov and G. Klein and I. Motylev and Belenkiy, {D. I.} and A. Demin and Nikolaev, {K. Y.} and V. Oleynikov and K. Zrazhevskiy and I. Katelnitskiy and L. Khaisheva and S. Aksentiev and A. Nedoshivin and Popova, {V. B.} and Agafina, {A. S.} and M. Ballyuzek and E. Baranova and N. Burova and S. Eryshev and A. Filippov and Goloshchekin, {B. M.} and V. Konstantinov and Kostenko, {V. A.} and Simanenkov, {V. I.} and A. Volkova and D. Duplyakov and O. Reshetko and Y. Shvarts and Kuznetsov, {V. A.} and Samoylova, {Y. G.} and V. Tolkacheva and Shalaev, {S. V.} and Khokhlov, {A. L.} and A. Malygin and Shilkina, {N. P.} and Yakusevich, {V. V.} and R. Margoczy and V. Zubek and A. Dzupina and J. Dubrava and K. Dulkova and L. Fabryova and L. Gaspar and G. Kamensky and M. Kokles and K. Raslova and I. Soosova and J. Stevlik and J. Strbova and J. Sumbal and R. Uhliar and J. Micik and J. Truban and J. Fedacko and E. Pastrnakova and D. Pella and F. Fazekas and V. Ambrovicova and P. Kycina and E. Martinka and J. Nociar and M. Belicova and M. Banik and D. Kanderkova and M. Hranai and T. Duris and B. Krahulec and J. Benacka and D. Vinanska and E. Roskova and D. Skripova and V. Macek and B. Vohnout and I. Buganova and Engelbrecht, {J. M.} and Pretorius, {M. M.} and Ebrahim, {I. O.} and J. Bayat and S. Ganesh and N. Ranjith and Coetzer, {T. F.} and A. Jacovides and Distiller, {L. A.} and Hellig, {F. S.} and Engelbrecht, {I. V.} and Mahomed, {A. A.} and Blignault, {S. C.} and Burgess, {L. J.} and Kotze, {H. J.} and {van Nieuwenhuizen}, E. and Musungaie, {D. B.} and S. Emanuel and {van der Walt}, E. and Pretorius, {C. E.} and Roos, {J. S.} and Roux, {S. M.} and Badat, {A. E.} and L. Fouche and Vahed, {Y. A. K.} and {van Resburg}, {D. Jansen} and {van Zyl}, {L. J.} and {Soto Gonzalez}, A. and Diaz, {J. L.} and T. Segura and {Botella Serrano}, M. and {Botas Rodrigues}, J. and Molto-Jorda, {J. M.} and {Dominguez Escribano}, {J. R. R.} and {Sogorb Garri}, F. and {Blanco Coronado}, {J. L.} and {Gaztambide Saenz}, {M. S.} and {Brotons Cuixart}, C. and {Garcia-Moll Marimon}, X. and {Gonzalbez Morgaez}, {J. D.} and {Maisterra Santos}, O. and {Roquer Gonzalez}, J. and J. Sobrino-Martinez and {Chueca Fernandez}, {J. E.} and S. Narejos and {Suarez Garcia}, S. and {Perez Martinez}, P. and {Figueras Camos}, R. and {Medrano Martinez}, V. and {Bellido Guerrero}, D. and {Martinez Deben}, F. and {Vila Belmonte}, A. and {Mediavilla Garcia}, {J. D.} and {Romero Hinojosa}, {J. A.} and {Martorell Mateu}, E. and {Cequier Fillat}, {A. R.} and {Pinto Sala}, X. and {Adroer Martori}, R. and {Bueno Diez}, M. and {Lopez Cano}, C. and {Worner Diz}, F. and {Gonzalez Juanatey}, C. and {Alvarez-Sala Walther}, {L. A.} and {Garcia Diaz}, {J. De Dios} and {Garcia Puig}, J. and {Jodar Gimeno}, E. and {Plaza Perez}, I. and C. Suarez-Fernandez and J. Tunon and {Zamorano Gomez}, {J. L.} and {Brito Sanfiel}, {M. A.} and {Escudier Villa}, {J. M.} and {de Mora Martin}, M. and {Dominguez Lopez}, M. and {Hernandez Garcia}, {J. M.} and {Tinahones Madueno}, {F. J.} and {Perez Paredes}, M. and {Aracil Villar}, J. and {Barreda Gonzalez}, {M. J.} and {Ripoll Vera}, {T. V.} and {Tofe Povedano}, S. and {Sanchez Alvarez}, J. and {Martinez Via}, L. and {Robles Iniesta}, A. and L. Masana and {Vinyoles Bargallo}, E. and {Calvo Gomez}, C. and {Gonzalez Juanatey}, {J. R.} and {Cruz Fernandez}, {J. M.} and {De La Cuesta Mayor}, C. and {Duran Garcia}, S. and {Jimenez Hernandez}, {M. D.} and {Morales Portillo}, C. and {Muniz Grijalvo}, O. and {De Castro}, R. and {Taverna Llaurado}, E. and {Pons Amate}, {J. M.} and {Terns Riera}, M. and {Civeira Murillo}, F. and C. Linderfalk and D. Curiac and K. Saldeen-Nilehn and P. Koskinen and P. Khalili and I. Tortensson and C-J Lindholm and A. Luts and Koskinen, {P. T.} and A. Gottsater and Persson, {B. E.} and T. Mooe and H. Larnefeldt and K. Boman and M. Crisby and G. Rasmanis and B-O Tengmark and N. Witt and E. Hagstrom and J. Viklund and C. Muller and F. Mach and M. Burnier and D. Nanchen and G. Wuerzner and M. Banyai and T. Moccetti and Miserez, {A. R.} and S. Bilz and K. Weber and W-T Lai and K-C Chang and K-C Ueng and W-C Tsai and C-E Chiang and C. Hou and D. Pei and R. Krittayaphong and S. Kiatchoosakun and S. Srimahachota and A. Boonyavarakul and W. Jintapakorn and H. Gullu and E. Onrat and Erkan, {A. F.} and D. Demirci and R. Sari and C. Ceyhan and H. Ari and M. Araz and M. Degertekin and O. Goktekin and Uresin, {A. Y.} and Z. Yigit and B. Akdeniz and A. Comlekci and M. Kayikcioglu and T. Sahin and T. Ozcan and E. Durakoglugil and N. Asamoah-Owusu and R. Reed and A. Bakhai and L. Dixon and R. Sharma and Avornyo, {A. A.} and Jones, {A. F.} and G. Lip and R. Clark and M. Banerjee and J. Wakeling and C. Arden and Blagden, {M. D.} and P. Walukiewica and A. Marshall and Maxwell, {T. G.} and Gunstone, {A. E.} and Kadr, {H. H.} and R. Patle and I. Arif and Jhund, {P. S.} and G. McKaig and F. Douglas and L. Mierzejewski and W. Turner and T. Sathyapalan and P. Ivan and A. Manoj and S. Rice and Collier, {D. J.} and Nair, {D. R.} and S. Thom and G. Fiore and {De Belder}, M. and D. Price and J. Sobolewska and S. Martin and A. Takhar and A. Moriarty and V. Kondagunta and T. Myhill and Gibson, {J. M.} and Cecil, {J. T.} and J. Halcox and N. Annamalai and Gorog, {D. A.} and T. McCormack and N. Pegge and A. Field and F. Adams and Klein, {J. J.} and Busch, {R. S.} and Bretton, {E. M.} and N. Jaffrani and A. Salacata and A. Assadourian and Gogia, {H. S.} and Dyke, {C. K.} and M. Rubenfire and Essandoh, {L. K.} and Welker, {J. A.} and G. Ledesma and S. Lupovitch and Delgado, {J. P.} and Hendrix, {E. L.} and Quyyumi, {A. A.} and Riesenberg, {R. A.} and Robertson, {D. G.} and Weinstein, {D. L.} and R. Weiss and L. Casaubon and Gammon, {R. S.} and Brar, {H. S.} and Bittar, {G. D.} and Guarnieri, {T. T.} and Incer, {C. S., Jr.} and Quraishi, {A. M.} and S. Saeed and M. Albert and Sotolongo, {R. P.} and Bernard, {J. V.} and Karlsbergg, {R. P.} and Lepor, {N. E.} and Kirby, {W. E.} and B. McLean and Miller, {A. P.} and F. Ovalle and Townsend, {J. C.} and Beckett, {P. L.} and Eaves, {W. B.} and West, {S. H.} and Kosinski, {E. J.} and Zarich, {S. W.} and Mahal, {S. S.} and K. Maw and Maynard, {K. M.} and Chen, {J. C.} and J. Gelormini and Gottlieb, {D. W.} and Gabra, {N. W.} and P. Narayan and J. Sparks and Field, {J. C.} and Willits, {V. L.} and O'Steen, {M. B.} and Pasquini, {J. A.} and Sensebrenner, {J. W.} and Yarows, {S. A.} and L. Hiotis and Jagielo, {T. J.} and Levinson, {D. J.} and Diller, {P. M.} and Kereiakes, {D. J.} and Turner, {T. A.} and S. Vincent and Camp, {A. D.} and Denker, {P. S.} and Manning, {M. B.} and Rocco, {M. B.} and Stamps, {H. B.} and Strader, {J. R.} and Uusinarkaus, {K. T.} and Kennett, {J. D.} and Leichter, {S. B.} and McNeil, {D. L.} and Schumacher, {D. R.} and Chang, {A. R.} and Ellison, {H. S.} and Updegrove, {J. D.} and Hamroff, {G. S.} and Kay, {J. S.} and Marar, {I. E.} and E. Flores and S. Saini and S. Abdullah and Berk, {M. R.} and S. Fordan and Joshi, {P. H.} and McCullough, {P. A. A.} and Reynolds, {R. D.} and J. Rosenstock and Sachson, {R. A.} and N. Shammas and Fishbein, {G. J.} and Randall, {W. J.} and Henderson, {D. A.} and Nash, {M. L.} and Barker, {B. A.} and Cohen, {S. S.} and B. Seidman and Odekirk, {L. L.} and Grillo, {R. S.} and Martinez, {L. M.} and P. Multani and Alwine, {L. K.} and McGarvey, {J. F.} and Mollerus, {M. E.} and Miller, {A. B.} and Kotek, {L. W.} and M. Changlani and Zavaro, {S. H.} and F. Munoz and Mehta, {P. M.} and Helm, {R. J.} and Farhat, {N. Z.} and R. Farsad and Raoof, {T. J.} and Shultz, {J. H.} and Geohas, {J. G.} and Allaw, {M. A.} and {Dela Llana}, A. and Gutmann, {J. E.} and Inzerello, {A. T.} and P. Alappat and George, {A. R.} and Haddad, {T. M.} and Lillestol, {M. J.} and R. Grodman and Peniston, {J. H.} and K. Wadud and B. Garcia and Hamilton, {M. E.} and S. Lerman and Perloff, {D. E.} and A. Graff and S. Saxena and Alvarado, {O. P.} and A. Malik and Reddy, {R. D.} and G. Kinzfogl and Cornett, {G. M.} and Norwood, {P. C.} and Gilbert, {J. M.} and Willis, {J. G.} and F. McGrew and S. Sharma and Castro, {M. A.} and Cucher, {F. H.} and Altafullah, {I. M.} and S. Khurana and Knutson, {T. J.} and Kinnaman, {S. J.} and T. Stuckey and Pudi, {K. K.} and Mayfield, {R. K.} and Funk, {G. S.} and Nixon, {W. A.} and I. Dor and Boyett, {B. E.} and S. Srivastava and Elosegui, {A. M.} and Isserman, {S. M.} and Cheek, {H. B.} and Promisloff, {S. D.} and Tami, {L. F.} and S. Zeig and D. Fitz-Patrick and Dave, {K. N.} and A. Ahmad and S. Arain and Ballantyne, {C. M.} and A. Doshi and {El Hafi}, {S. E.} and J. Feldman and Fragoso, {V. G.} and T. Gilford and Hoffman, {A. S.} and Pouzar, {J. E.} and K. Vivekananthan and Ansari, {S. H.} and Strzinek, {R. A.} and Crater, {T. A.} and Robinson, {J. G.} and Fulmer, {J. J.} and Patel, {A. M.} and Pereira, {E. S.} and Stich, {M. A.} and S. Sultan and G. Geskin and Ruoff, {G. E.} and E. Gillespie and Bybee, {K. A.} and Moriarty, {P. M.} and V. Savin and Agaiby, {J. M.} and Melucci, {M. B.} and Jantzi, {C. M.} and E. Davidson and Smith, {W. B.} and Treasure, {C. B.} and Wakefield, {P. H.} and K. Deck and Edris, {M. A.} and Gilmore, {R. M.} and Seep, {M. K.} and Andersen, {J. L.} and Detweiler, {R. O.} and Rosenfeld, {J. C.} and Strobl, {D. J.} and Steinhoff, {J. P.} and A. Adams and R. Estevez and Molin, {C. J.} and Kim, {C. Y.} and J. Dy and Fox, {K. E.} and Farris, {N. R.} and Wayne, {J. D.} and Whitney, {R. T.} and Randhawa, {P. M.} and Mego, {D. M.} and L. MacDolnald and Caputo, {R. P.} and R. Rigolosi and B. VanNatta and Pacheco, {T. R.} and M. El-Shahawy and Gonzalez, {E. J.} and Guice, {M. J.} and Cherlin, {R. S.} and Bays, {H. E.} and M. Shoukfeh and Morris, {F. H.} and J. Loy and Vora, {S. K.} and Staab, {P. K.} and A. Frisoli and Kimmel, {M. A.} and Cohen, {A. J.} and Green, {C. B.} and L. Whitlock and Butuk, {D. J.} and McCartney, {M. J.} and Ables, {L. R.} and R. Acosta and Alvarez, {J. G.} and Barrera, {C. M.} and O. Benitez and Berenguer, {R. A.} and Breton, {C. F.} and R. Chiong and Delgado, {M. I.} and A. Dufreny and Fialkow, {J. A.} and S. Franczek and Frias, {J. J.} and C. Iglesias and L. Landron-Garcia and Llerena, {S. N.} and Martinez, {R. F.} and Miranda, {A. A.} and Morytko, {J. A.} and Rodriguez, {I. J.} and R. Sotolongo and A. Suarez-Sarmiento and Terrelonge, {A. E.} and Vaca, {C. E.} and Venereo, {J. M.} and C. Verdeza and Zeno, {M. L.} and S. Chilka and Felten, {W. R.} and Hartman, {A. N.} and Shayani, {S. S.} and D. Duprez and T. Knickelbine and Chambers, {J. D.} and Cone, {C. L.} and R. Broughton and Napoli, {M. C.} and Seaton, {B. L.} and Smith, {S. K.} and Reedy, {M. A.} and Kesani, {M. K.} and Nicol, {P. R.} and Stringam, {S. O.} and Talano, {J. V.} and O. Barnum and V. Desai and M. Montero and Jacks, {R. K.} and Kostis, {J. B.} and Owen, {J. G.} and Makam, {S. K.} and I. Grosman and Underberg, {J. A.} and Masri, {B. E.} and Peters, {S. S.} and J. Serje and Lenhard, {M. J. J.} and R. Glover and Paraboschi, {C. F.} and Lim, {E. H.} and L. Connery and W. Kipgen and P. Bravo and DiGiovanna, {M. J.} and H. Tayoum and Gabriel, {J. D.} and Ariani, {M. K.} and Robinson, {M. F.} and Clemens, {P. C.} and Corder, {C. N.} and B. Schifferdecker and Tahirkheli, {N. K.} and Hurling, {R. T.} and Rendell, {M. S.} and V. Shivaswamy and I-J Madu and Dahl, {C. F.} and K. Ayesu and C. Kim and Barettella, {M. B.} and Jamidar, {H. A.} and Bloom, {S. A.} and Vora, {K. N.} and Ong, {S. T.} and G. Aggarwala and G. Sack and K. Blaze and P. Krichmar and A. Murcia and M. Teltser and Y. Villaman-Bencosme and Fahdi, {I. E.} and Williams, {D. G.} and Lain, {E. L.} and Garcia, {H. L.} and Karim, {S. N.} and Francyk, {D. M.} and Gordon, {M. B.} and Palchick, {B. A.} and McKenzie, {M. E.} and Gimness, {M. P.} and J. Greiff and L. Ruiz-R and Vazquez-Tanus, {J. B.} and D. Schlager and T. Connelly and E. Soroka and Hastings, {W. L.} and O'Dea, {D. J.} and Purdy, {D. A.} and B. Jackson and Arcanese, {M. L.} and Strain, {J. E.} and Schmedtje, {J. F., Jr.} and Davis, {M. G.} and A. Labroo and S. Prasada and Scott, {D. L.} and G. Vukotic and N. Akhtar and Larsen, {D. C.} and Rhudy, {J. M.} and Zebrack, {J. S.} and Bailey, {S. R.} and Grant, {D. C.} and A. Mora and Perez, {J. A.} and Reyes, {R. G.} and Sutton, {J. C.} and Brandon, {D. M.} and First, {B. P.} and Brian and Risser, {J. A.} and J. Claudio and Figueroa-Cruz, {W. L.} and Sosa-Padilla, {M. A.} and Tan, {A. E.} and Traboulssi, {M. A.} and Morcos, {N. C.} and Glaser, {L. A.} and Bredlau, {C. E.} and Ramos, {M. J.} and Kandath, {D. D.} and E. Kaluski and L. Akright and Rictor, {K. W.} and Pluto, {T. M.} and Hermany, {P. R.} and B. Bellingar and Clark, {G. B.} and Herrod, {J. N.} and M. Goisse and M. Hook and P. Barrington and Lentz, {J. D.} and Singal, {D. K.} and Gleason, {G. P.} and Lipetz, {R. S.} and Schuchard, {T. N.} and Bonner, {J. H.} and Forgosh, {L. B.} and Lefebvre, {G. C.} and Pierpoint, {B. E.} and Radin, {D. M.} and Stoller, {S. R.} and N. Segall and Shah, {S. A.} and Ramstad, {D. S.} and Nisnisan, {J. M.} and Trippett, {J. M.} and Benjamin, {S. A.} and J-C Labissiere and Nashed, {A. N.} and M. Maaieh and Aslam, {A. A.} and M. Mandviwala and Budoff, {M. J.} and French, {W. J.} and Vlach, {J. J.} and P. DeStefano and Bayron, {C. J.} and Fraser, {N. J.} and Sandberg, {J. H.} and Fagan, {T. C.} and Peart, {B. C.} and Suryanarayana, {P. G.} and Gupta, {D. K.} and Lee, {M. W.} and Bertolet, {B. D.} and Hartley, {P. A.} and M. Kelberman and B. Behmanesh and Buynak, {R. J.} and Chochinov, {R. H.} and Steinberg, {A. A.} and H. Chandna and Bjasker, {K. R.} and Perlman, {R. L.} and Ball, {E. M.} and J. Pock and S. Singh and D. Baldari and Sr Kaster and Lovell, {J. P.} and Horowitz, {B. S.} and Gorman, {T. A.} and Pham, {D. N.} and Landzberg, {J. S.} and Mootoo, {K. I.} and E. Moon and J. Krawczyk and Alfieri, {A. D.} and Janik, {M. J.} and Herrington, {D. M.} and Koilpillai, {R. N.} and Waxler, {A. R.} and Hoffman, {D. A.} and Sahul, {Z. H.} and Barry Gumbiner and Anne Cropp and Kayo Fujita and Pamela Garzone and Keiji Imai and Matteo Levisetti and David Plowchalk and Stephen Sasson and Judy Skaggs and Kevin Sweeney and John Vincent",
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 = "Massachussetts Medical Society",
number = "16",
}