机构：[1]Assistance Publique-Hopitaux de Paris, Hopital Bichat, Université de Paris, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France[2]National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom[3]State University of New York, Downstate School of Public Health, Brooklyn[4]Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA[5]Division of Cardiovascular Disease, University of Alabama at Birmingham[6]Sanofi, Paris, France[7]Milpark Hospital, Johannesburg, Republic of South Africa[8]Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Argentina[9]Sanofi, Bridgewater, NJ[10]Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada and St. Michael’s Hospital, University of Toronto, Canada[11]Stanford Center for Clinical Research, Department of Medicine, Stanford University, CA[12]Department of Cardiology, Leiden University Medical Center, the Netherlands[13]Na Homolce Hospital, Prague, Czech Republic[14]Institute of Cardiology, Kyiv, Ukraine[15]Regeneron Pharmaceuticals Inc, Tarrytown, NY[16]Duke Clinical Research Institute, Duke University Medical Center, Durham, NC[17]Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC[18]University of Colorado Denver[19]Green Lane Cardiovascular Services Auckland City Hospital, New Zealand[20]Department of Medicine III, Goethe University, Frankfurt am Main, Germany[21]Division of Cardiology, University of Colorado School of Medicine, Aurora
Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for >= 3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C >= 100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P-interaction=0.007). In the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for >= 3 years, if baseline LDL-C is >= 100 mg/dL, or if achieved LDL-C is low.
基金：
The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc.
第一作者机构：[1]Assistance Publique-Hopitaux de Paris, Hopital Bichat, Université de Paris, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France[2]National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom[*1]INSERM U1148, Université Paris Diderot, Département de Cardiologie, H魀ital Bichat, 46 Rue Henri Huchard, 75018 Paris, France.
共同第一作者：
通讯作者：
通讯机构：[1]Assistance Publique-Hopitaux de Paris, Hopital Bichat, Université de Paris, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France[2]National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom[*1]INSERM U1148, Université Paris Diderot, Département de Cardiologie, H魀ital Bichat, 46 Rue Henri Huchard, 75018 Paris, France.
推荐引用方式(GB/T 7714)：
Philippe Gabriel Steg,Michael Szarek,Deepak L. Bhatt,et al.Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial[J].CIRCULATION.2019,140(2):103-112.doi:10.1161/CIRCULATIONAHA.118.038840.
APA：
Philippe Gabriel Steg,Michael Szarek,Deepak L. Bhatt,Vera A. Bittner,Marie-France Brégeault...&Gregory G. Schwartz.(2019).Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial.CIRCULATION,140,(2)
MLA：
Philippe Gabriel Steg,et al."Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial".CIRCULATION 140..2(2019):103-112
医学