TY - JOUR
T1 - Alirocumab and cardiovascular outcomes after acute coronary syndrome
AU - ODYSSEY OUTCOMES Committees and Investigators
AU - Schwartz, G. G.
AU - Steg, P. G.
AU - Szarek, M.
AU - Bhatt, D. L.
AU - Bittner, V. A.
AU - Diaz, R.
AU - Edelberg, J. M.
AU - Goodman, S. G.
AU - Hanotin, C.
AU - Harrington, R. A.
AU - Jukema, J. W.
AU - Lecorps, G.
AU - Mahaffey, K. W.
AU - Moryusef, A.
AU - Pordy, R.
AU - Quintero, K.
AU - Roe, M. T.
AU - Sasiela, W. J.
AU - Tamby, J. F.
AU - Tricoci, P.
AU - White, H. D.
AU - Zeiher, A. M.
AU - Aylward, Philip E.
AU - Drexel, Heinz
AU - Sinnaeve, Peter
AU - Dilic, Mirza
AU - Lopes, Renato D.
AU - Gotcheva, Nina N.
AU - Prieto, Juan Carlos
AU - Yong, Huo
AU - Lopez-Jaramillo, Patricio
AU - Pecin, Ivan
AU - Reiner, Zeljko
AU - Ostadal, Petr
AU - Poulsen, Steen Hvitfeldt
AU - Viigimaa, Margus
AU - Nieminen, Markku S.
AU - Danchin, Nicolas
AU - Chumburidze, Vakhtang
AU - Marx, Nikolaus
AU - Liberopoulos, Evangelos
AU - Valdovinos, Pablo Carlos Montenegro
AU - Tse, Hung Fat
AU - Kiss, Robert Gabor
AU - Xavier, Denis
AU - Zahger, Doron
AU - Valgimigli, Marco
AU - Kimura, Takeshi
AU - Kim, Hyo Soo
AU - Hsieh, I. Chang
N1 - Publisher Copyright:
© 2018 Massachusetts Medical Society.
PY - 2018/11/29
Y1 - 2018/11/29
N2 - BACKGROUND Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), would improve cardiovascular outcomes after an acute coronary syndrome in patients receiving high-intensity statin therapy. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an acute coronary syndrome 1 to 12 months earlier, had a low-density lipoprotein (LDL) cholesterol level of at least 70 mg per deciliter (1.8 mmol per liter), a non-highdensity lipoprotein cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter), or an apolipoprotein B level of at least 80 mg per deciliter, and were receiving statin therapy at a high-intensity dose or at the maximum tolerated dose. Patients were randomly assigned to receive alirocumab subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks. The dose of alirocumab was adjusted under blinded conditions to target an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter). The primary end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. RESULTS The median duration of follow-up was 2.8 years. A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001). A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73 to 0.98). The absolute benefit of alirocumab with respect to the composite primary end point was greater among patients who had a baseline LDL cholesterol level of 100 mg or more per deciliter than among patients who had a lower baseline level. The incidence of adverse events was similar in the two groups, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group). CONCLUSIONS Among patients who had a previous acute coronary syndrome and who were receiving highintensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alirocumab than among those who received placebo.
AB - BACKGROUND Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), would improve cardiovascular outcomes after an acute coronary syndrome in patients receiving high-intensity statin therapy. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an acute coronary syndrome 1 to 12 months earlier, had a low-density lipoprotein (LDL) cholesterol level of at least 70 mg per deciliter (1.8 mmol per liter), a non-highdensity lipoprotein cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter), or an apolipoprotein B level of at least 80 mg per deciliter, and were receiving statin therapy at a high-intensity dose or at the maximum tolerated dose. Patients were randomly assigned to receive alirocumab subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks. The dose of alirocumab was adjusted under blinded conditions to target an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter). The primary end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. RESULTS The median duration of follow-up was 2.8 years. A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001). A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73 to 0.98). The absolute benefit of alirocumab with respect to the composite primary end point was greater among patients who had a baseline LDL cholesterol level of 100 mg or more per deciliter than among patients who had a lower baseline level. The incidence of adverse events was similar in the two groups, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group). CONCLUSIONS Among patients who had a previous acute coronary syndrome and who were receiving highintensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alirocumab than among those who received placebo.
UR - http://www.scopus.com/inward/record.url?scp=85057337718&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1801174
DO - 10.1056/NEJMoa1801174
M3 - 文章
C2 - 30403574
AN - SCOPUS:85057337718
SN - 0028-4793
VL - 379
SP - 2097
EP - 2107
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 22
ER -