Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome ODYSSEY OUTCOMES Trial

被引：174

作者：

Jukema, J. Wouter ^{[1
]}

Szarek, Michael ^{[2
]}

Zijlstra, Laurien E. ^{[1
]}

de Silva, H. Asita ^{[3
,71
]}

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

Bittner, Vera A. ^{[6
]}

Diaz, Rafael ^{[7
]}

Edelberg, Jay M. ^{[8
]}

Goodman, Shaun G. ^{[9
,11
]}

Hanotin, Corinne ^{[12
]}

Harrington, Robert A. ^{[13
]}

Karpov, Yuri ^{[14
,64
,925
]}

Moryusef, Angle ^{[8
]}

Pordy, Robert ^{[15
]}

Prieto, Juan C. ^{[16
,305
]}

Roe, Matthew T. ^{[17
,18
,80
]}

White, Harvey D. ^{[19
]}

Zeiher, Andreas M. ^{[20
]}

Schwartz, Gregory G. ^{[21
]}

Steg, P. Gabriel ^{[22
,23
,24
]}

Tricoci, Pierluigi ^{[90
]}

Mahaffey, Kenneth W. ^{[91
]}

Lecorps, Guillaume ^{[12
]}

Moryusef, Angele

Pordy, Robert ^{[15
]}

Sasiela, William J.

Tamby, Jean-Francois ^{[12
]}

Aylward, Philip E. ^{[25
,157
]}

Drexel, Heinz ^{[26
,177
]}

Sinnaeve, Peter ^{[27
,186
]}

Dilic, Mirza ^{[28
]}

Gotcheva, Nina N. ^{[29
,260
]}

Goodman, Shaun G. ^{[9
,11
]}

Prieto, Juan-Carlos ^{[30
]}

Yong, Huo ^{[31
]}

Lopez-Jaramillo, Patricio ^{[32
]}

Pecin, Ivan ^{[33
]}

Reiner, Zeljko ^{[34
]}

Ostadal, Petr ^{[35
,429
]}

Poulsen, Steen Hvitfeldt ^{[36
,434
]}

Viigimaa, Margus ^{[37
]}

Nieminen, Markku S. ^{[38
]}

Danchin, Nicolas ^{[39
,466
]}

Chumburidze, Vakhtang ^{[40
,484
]}

Marx, Nikolaus ^{[41
,503
]}

Liberopoulos, Evangelos ^{[42
,531
]}

Valdovinos, Pablo Carlos Montenegro ^{[43
,539
]}

Tse, Hung-Fat ^{[44
]}

Kiss, Robert Gabor ^{[45
,546
]}

Xavier, Denis ^{[46
]}

机构：

[1] Leiden Univ, Dept Cardiol, Med Ctr, POB 9600, NL-2300 RC Leiden, Netherlands

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

[3] Univ Kelaniya, Fac Med, Clin Trials Unit, Kelaniya, Sri Lanka

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

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

[6] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA

[7] Cardiovasc Inst Rosario, Latinoamer Cardiol Studies, Rosario, Santa Fe, Argentina

[8] Sanofi, Bridgewater, NJ USA

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

[10] Covance, Marlow, Bucks, England

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

[12] Sanofi, Paris, France

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

[14] Russian Cardiol Sci Product Complex, Moscow, Russia

[15] Regeneron Pharmaceut Inc, Tarrytown, NY USA

[16] Univ Chile Clin Hosp, Santiago, Chile

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

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

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

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

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

[22] Hop Bichat Claude Bernard, AP HP, Paris, France

[23] Paris Diderot Univ, Sorbonne Paris Cite, FACT, INSERM U1148, Paris, France

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

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

[26] Landeskrankenhaus Feldkirch, Feldkirch, Austria

[27] UZ Leuven, Leuven, Belgium

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

[29] MHAT Nat Cardiol Hosp EAD, Sofia, Bulgaria

[30] Univ Chile, Hosp Clin, Santiago, Chile

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

[32] Fundac Oftalmol Santander FOSCAL, Floridablanca, Colombia

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

[34] Univ Zagreb, Univ Ctr Zagreb, Sch Med, Zagreb, Croatia

[35] Na Homolce Hosp, Prague, Czech Republic

[36] Aarhus Univ Skejby, Aarhus, Denmark

[37] North Estonia Med Ctr, Tallinn, Estonia

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

[39] Hop Europeen Georges Pompidou, FACT, F CRIN Network, Paris, France

[40] Chapidze Emergency Cardiol Ctr, Tbilisi, Georgia

[41] Univ Aachen, Aachen, Germany

[42] Univ Gen Hosp Ioannina, Ioannina, Greece

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

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

[45] Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary

[46] St Johns Med Coll, Bangalore, Karnataka, India

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

[48] Univ Ferrara, Unit Operativa Cardiologia, Ferrara, Italy

[49] Kyoto Univ, Grad Sch Med, Kyoto, Kyoto, Japan

[50] Seoul Natl Univ Hosp, Seoul, South Korea

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2019年 / 74卷 / 09期

关键词：

acute coronary syndrome; alirocumab; cerebrovascular disease; death; major adverse cardiac events; peripheral artery disease; CARDIOVASCULAR EVENT RATES; ARTERY-DISEASE; PCSK9; INHIBITION; RISK; OUTPATIENTS; CHOLESTEROL; MANAGEMENT; INSIGHTS;

D O I：

10.1016/j.jacc.2019.03.013

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined. OBJECTIVES This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. METHODS Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. RESULTS Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). CONCLUSIONS In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402) (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

引用

页码：1167 / 1176

页数：10

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