BACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets.
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[10.1056/NEJMoa1615664]
Evolocumab and clinical outcomes in patients with cardiovascular disease
Sabatine, Marc S. Giugliano, Robert P.; Keech, Anthony C.; Honarpour, Narimon; Wiviott, Stephen D.; Murphy, Sabina A.; Kuder, Julia F.; Wang, Huei; Liu, Thomas; Wasserman, Scott M.; Sever, Peter S.; Pedersen; Terje R. Fish MP; Abrahamsen TE; Im K; Kanevsky E; Bonaca MP; Lira Pineda A; Hanlon K; Knusel B; Somaratne R; Kurtz C; Scott R; Accini Mendoza JL; Amerena J; Badariene J; Burgess L; Ceska R; Charng MJ; Choi D; Cobos JL; Dan GA; De Ferrari GM; Deedwania PC; Chopra VK; Erglis A; Ezhov MV; Ferreira J; Filipová S; Gaciong ZA; Pasierski T; Georgiev BG; Gonzalez-Galvez G; Gouni-Berthold I; Schäufele T; Hirayama A; Huber K; Rammer M; Kjaerulf Jensen H; Wermuth S; Jiang L; Jukema JW; Kraydashenko O; Leiter LA; Lewis BS; López-Miranda J; Lorenzatti AJ; Mach F; McAdam B; Nilsson L; Olsson Å; Rallidis L; Rogelio GG; Kerr Saraiva JF; Scheen A; Schiele F; Scott RS; Connolly D; Siu CW; Tay L; Thorgeirsson G; Tikkanen MJ; Tokgozoglu SL; Toth K; Viigimaa M; Wan Ahmad WA; Hennekens CH; Andreotti F; Baigent C; Brown WV; Davis BR; Newcomer JW; Wood SK; LaRosa J; Ansell B; Olsson A; Lowe C; Zahn L; Awtry E; Berger C; Croce K; Desai A; Gelfand E; Ho C; Leeman D; Link M; Norden A; Pande A; Rost N; Ruberg F; Silverman S; 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Soares Piegas L; Cunha Borges JL; Ferreira Rossi PR; Pimentel Filho P; Bodanese LC; de Sa Cunha R; Moura Jorge JC; Ardito WR; Barroso de Souza WK; Hissa M; Izar MC; Manolova A; Kitova L; Kinova E; Tzekova M; Velchev V; Tarnovska-Kadreva R; Gotchev D; Petrov I; Raev D; Trendafilova-Lazarova D; Yotov Y; Lazov P; Rahimi S; St Amour E; Constance C; Pesant Y; Hess A; Anderson T; Sussex B; Henein S; Tsoukas G; Pandey AS; Bergeron J; Hart R; Gosselin G; Chehayeb R; Hamet P; Hartleib M; Mukherjee A; Halperin F; Petrella R; Bhargava R; Lonn E; Sabbah E; Bata I; Cha J; Gaudet D; Chapman K; Murthy D; Nigro F; Rupka D; Gossard D; Gupta M; Dowell A; Mansour S; Baass A; Geadah C; Huynh T; Peterson S; Poirier P; Sabe-Affaki G; Vertes G; Crowley D; Duchesne L; Pincetti Jofre CP; Potthoff Cardenas S; Conejeros Kindel C; Saavedra Gajardo VA; Lanas Zanetti F; Sepulveda Varela PA; Stockins Fernandez BA; Li W; Li D; Zhao S; Li Z; Wang J; Yang Y; Zhang L; Yang P; Zhang X; Huang H; Xue L; Zheng Z; Huang W; Dai H; 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Violante Ortiz RM; Illescas Diaz JJ; Leon Gonzalez S; Sanchez Diaz CJ; Mendez Machado GF; Venegas Carrillo LA; Aldrete Velasco JA; Cardona Muñoz EG; Leiva Pons JL; Perez Alva JC; van der Zwaan C; Oomen A; van de Wal R; Magro M; Boswijk D; Janus C; Groutars R; Tonino W; Cornel JH; Oude Ophuis A; Troquay R; Liem A; Westendorp I; Van Hessen M; Lok D; De Nooijer C; Den Hartog F; Van Beek E; Bendermacher P; Jansen R; Römer T; Rensing B; Hersbach F; Herrman J; Ladyjanskaia G; Karalis I; Linssen G; Bokern M; Visman A; Kooij A; Monajemi H; Lieverse A; Baker J; Tie S; Risberg K; Hysing J; Pedersen T; Hoivik HO; Norheim P; Solnor L; Hovland A; Kjaernli T; Jocson G; Coching RM; Batalla E; Go A; Habaluyas R; Barcinas R; Sy RA; Estepar RA; Germar A; Trebacz J; Szymkowiak K; Wnetrzak-Michalska R; Kopaczewski J; Przekwas-Jaruchowska M; Kania G; Zabowka M; Mirek-Bryniarska E; Dabrowska M; Napora P; Konieczny M; Spyra J; Lysek R; Pijanowski Z; Grzegorzewski B; Bednarkiewicz Z; Kinasz L; Antkowiak-Piatyszek K; 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2017
Abstract
BACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets.
Citazione
Evolocumab and clinical outcomes in patients with cardiovascular disease / Sabatine, Marc S.; Giugliano, Robert P.; Keech, Anthony C.; Honarpour, Narimon; Wiviott, Stephen D.; Murphy, Sabina A.; Kuder, Julia F.; Wang, Huei; Liu, Thomas; Wasserman, Scott M.; Sever, Peter S.; Pedersen, ; Terje R., Fish MP; Abrahamsen, Te; Im, K; Kanevsky, E; Bonaca, Mp; Lira Pineda, A; Hanlon, K; Knusel, B; Somaratne, R; Kurtz, C; Scott, R; Accini Mendoza, Jl; Amerena, J; Badariene, J; Burgess, L; Ceska, R; Charng, Mj; Choi, D; Cobos, Jl; Dan, Ga; De Ferrari, Gm; Deedwania, Pc; Chopra, Vk; Erglis, A; Ezhov, Mv; Ferreira, J; Filipová, S; Gaciong, Za; Pasierski, T; Georgiev, Bg; Gonzalez-Galvez, G; Gouni-Berthold, I; Schäufele, T; Hirayama, A; Huber, K; Rammer, M; Kjaerulf Jensen, H; Wermuth, S; Jiang, L; Jukema, Jw; Kraydashenko, O; Leiter, La; Lewis, Bs; López-Miranda, J; Lorenzatti, Aj; Mach, F; McAdam, B; Nilsson, L; Olsson, Å; Rallidis, L; Rogelio, Gg; Kerr Saraiva, Jf; Scheen, A; Schiele, F; Scott, Rs; 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[10.1056/NEJMoa1615664]
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Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione.
