Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

被引：397

作者：

Bittner, Vera A. ^{[1
]}

Szarek, Michael ^{[2
]}

Aylward, Philip E. ^{[3
,30
]}

Bhatt, Deepak L. ^{[4
,5
]}

Diaz, Rafael ^{[6
]}

Edelberg, Jay M. ^{[7
]}

Fras, Zlatko ^{[8
,9
,74
,75
]}

Goodman, Shaun G. ^{[10
,11
]}

Halvorsen, Sigrun ^{[12
,13
,64
]}

Hanotin, Corinne ^{[14
]}

Harrington, Robert A. ^{[15
]}

Jukema, J. Wouter ^{[16
]}

Loizeau, Virginie ^{[14
]}

Moriarty, Patrick M. ^{[17
,87
,1138
]}

Moryusef, Angele ^{[7
]}

Pordy, Robert ^{[18
]}

Roe, Matthew T. ^{[19
,20
]}

Sinnaeve, Peter ^{[21
,22
,32
]}

Tsimikas, Sotirios ^{[23
]}

Vogel, Robert ^{[24
,88
]}

White, Harvey D. ^{[25
]}

Zahger, Doron ^{[26
,52
]}

Zeiher, Andreas M. ^{[27
]}

Steg, Gabriel ^{[28
,29
]}

Schwartz, Gregory G. ^{[24
]}

Aylward, Philip E. ^{[3
,30
]}

Drexel, Heinz ^{[31
,173
]}

Sinnaeve, Peter ^{[21
,22
,32
]}

Dilic, Mirza ^{[33
]}

Lopes, Renato D. ^{[1
,96
,238
]}

Gotcheva, Nina N. ^{[34
,254
]}

Prieto, Juan-Carlos ^{[35
,299
]}

Yong, Huo ^{[36
]}

Lopez-Jaramillo, Patricio ^{[37
]}

Pecin, Ivan ^{[38
]}

Reiner, Zeljko ^{[39
]}

Ostadal, Petr ^{[40
,401
]}

Poulsen, Steen Hvitfeldt ^{[41
]}

Viigimaa, Margus ^{[42
]}

Nieminen, Markku S. ^{[43
]}

Danchin, Nicolas ^{[44
]}

Chumburidze, Vakhtang ^{[45
]}

Marx, Nikolaus ^{[46
,470
]}

Liberopoulos, Evangelos ^{[47
,493
]}

Montenegro Valdovinos, Pablo Carlos ^{[48
]}

Tse, Hung-Fat ^{[49
]}

Kiss, Robert Gabor ^{[50
,507
]}

Xavier, Denis ^{[51
]}

Zahger, Doron ^{[26
,52
]}

Valgimigli, Marco ^{[53
]}

机构：

[1] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL USA

[2] SUNY, Downstate Sch Publ Hlth, Brooklyn, NY USA

[3] Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia

[4] Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA

[5] Harvard Med Sch, Boston, MA 02115 USA

[6] Inst Cardiovasc Rosario, Estudios Cardiol Latinoamer, Rosario, Argentina

[7] Sanofi, Bridgewater, MA USA

[8] Univ Med Ctr Ljubljana, Prevent Cardiol Unit, Div Med, Dept Vasc Med, Ljubljana, Slovenia

[9] Univ Ljubljana, Med Fac, Ljubljana, Slovenia

[10] Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada

[11] Univ Toronto, St Michaels Hosp, Toronto, ON, Canada

[12] Oslo Univ Hosp, Dept Cardiol, Oslo, Norway

[13] Univ Oslo, Oslo, Norway

[14] Sanofi, Paris, France

[15] Stanford Univ, Dept Med, Stanford Ctr Clin Res, Stanford, CA 94305 USA

[16] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands

[17] Univ Kansas, Med Ctr, Div Clin Pharmacol, Kansas City, KS 66103 USA

[18] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA

[19] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA

[20] Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA

[21] Univ Hosp Leuven, Dept Cardiovasc Med, Leuven, Belgium

[22] Univ Leuven, Leuven, Belgium

[23] Univ Calif San Diego, Div Cardiovasc Med, La Jolla, CA 92093 USA

[24] Univ Colorado, Div Cardiol, Sch Med, Aurora, CO USA

[25] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand

[26] Ben Gurion Univ Negev, Soroka Univ Med Ctr, Fac Hlth Sci, Beer Sheva, Israel

[27] Goethe Univ, Dept Med 3, Frankfurt, Germany

[28] Univ Paris, Hop Bichat, AP HP, FACT,INSERM,U1148, Paris, France

[29] Imperial Coll, Natl Heart & Lung Inst, Royal Brompton Hosp, London, England

[30] Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia

[31] Landeskrankenhaus Feldkirch, Feldkirch, Austria

[32] UZ Leuven, Leuven, Belgium

[33] Univ Clin Ctr Sarajevo, Sarajevo, Bosnia & Herceg

[34] MHAT Natl Cardiol Hosp EAD, Sofia, Bulgaria

[35] Hosp Clin Univ Chile, Santiago, Chile

[36] Peking Univ First Hosp, Beijing, Peoples R China

[37] Fdn Oftalmol Santander FOSCAL, Floridablanca, Colombia

[38] Univ Zagreb, Univ Hosp Ctr Zagreb, Zagreb Sch Med, Zagreb, Croatia

[39] Univ Zagreb, Univ Hosp Ctr Zagreb, Sch Med, Zagreb, Croatia

[40] Na Homolce Hosp, Prague, Czech Republic

[41] Aarhus Univ Hosp Skejby, Aarhus N, Denmark

[42] SA Pohja Eesti Reg Haigla, Tallinn, Estonia

[43] HUCH, Div Cardiol, Heart & Lung Ctr, Helsinki, Finland

[44] FACT, Hop Europeen Georges Pompidou, Paris, France

[45] Chapidze Emergency Cardiol Ctr, Tbilisi, Georgia

[46] Univ Klinikum Aachen, Aachen, Germany

[47] Univ Gen Hosp Ioannina, Ioannina, Greece

[48] Clin Privada, Unidad Diagnost Cardiol, Guatemala City, Guatemala

[49] Univ Hong Kong, Queen Mary Hosp, Hong Kong, Peoples R China

[50] Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2020年 / 75卷 / 02期

关键词：

acute coronary syndromes; alirocumab; low-density lipoprotein cholesterol; major adverse cardiovascular events; proprotein convertase subtilisin/kexin type 9 inhibition; REDUCING LIPIDS; EFFICACY; DISEASE; SAFETY; CHOLESTEROL; NIACIN;

D O I：

10.1016/j.jacc.2019.10.057

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). OBJECTIVES A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). METHODS One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. RESULTS Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). CONCLUSIONS Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

引用

页码：133 / 144

页数：12

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