2 research outputs found
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
- Author
- Aaltonen M
- Abdur Rahman M
- Abell T
- Abide W. Jr
- Acheatel R
- Achiri P
- Acon J
- Adams T
- Affinito S
- Agarwal S
- Aggarwal K
- Aggarwal R
- Ahlström P
- Ahmad A
- Ahmed M
- Aillon C
- Airaksinen A
- Ait-sadi R
- Akers J
- Al-jumaily J
- Albers C
- Albert M
- Alberti A
- Alexander T
- Alford C
- Algotsson L
- Allen T
- Allworth M
- Almond E
- Aloisi A
- Alternburg C
- Alton M
- Amin J
- Amundson A
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- Andersen M
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- Andresen D
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- Zhou Xingyu
- Zhou Yingyuan
- Zhu Wangqin
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- Zoghbi J
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- Zuchelkowski A
- Zulauf N
- Ågårdh A
- Öner A
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
- Author
- Abraham Aswin
- Adebiyi Akindele O.
- Adjei Andrew A.
- Adusei Ben
- Aisuodionoe-Shadrach Oseremen I.
- Ajibola Hafees O.
- Albanes Demetrius
- Aldrich Melinda C.
- Aly Markus
- Ambs Stefan
- Amodu Olukemi
- Andrews Caroline
- Andriole Gerald L.
- Asai Satoshi
- Aukim-Hastie Claire
- Auvinen Anssi
- Barnett Gill
- Batra Jyotsna
- Beane Freeman Laura E.
- Benlloch Sara
- Bensen Jeannette T.
- Berndt Sonja I.
- Biritwum Richard B.
- Blanchet Pascal
- Blot William J.
- Bohlender Ryan J.
- Bojesen Stig E.
- Borre Michael
- Brandão Andreia
- Brenner Hermann
- Brook Mark N.
- Brureau Laurent
- Bush William S.
- Butler Ebonee N.
- Cancel-Tassin Geraldine
- Cannon-Albright Lisa
- Carpten John
- Casey Graham
- Castaño-Vinyals Gemma
- Castelao Jose Esteban
- Chambers Suzanne
- Chanock Stephen J.
- Chen Fei
- Chen Xuechen
- Cho Kelly
- Chokkalingam Anand P.
- Chou Alisha J.
- Choudhury Parichoy P.
- Claessens Frank
- Clark Peter E.
- Clements Judith A.
- Conti David V.
- Cook Michael B.
- Crawford Dana C.
- Cullen Jennifer
- Cussenot Olivier
- Cybulski Cezary
- Dadaev Tokhir
- Darkwa-Abrahams Afua
- Darst Burcu F.
- De Meerleer Gert
- De Ruyck Kim
- Dierssen-Sotos Trinidad
- Ding Yuan Chun
- Diop Halimatou
- Donovan Jenny L.
- Drake Bettina F.
- Dunning Alison M.
- Easton Douglas F.
- Edwards Todd L.
- Eeles Rosalind A.
- Eklund Martin
- Fachal Laura
- Feng Ninghan
- Figuerêdo Jéssica
- Finelli Antonio
- Fleshner Neil E.
- Fowke Jay H.
- Fritsche Lars
- Fujita Masashi
- Furukawa Yoichi
- Gago-Dominguez Manuela
- Gamulin Marija
- Gaziano J. Michael
- Ghoussaini Maya
- Giles Graham G.
- Giovannucci Edward
- Goodman Phyllis J.
- Govindasami Koveela
- Grindedal Eli Marie
- Gronberg Henrik
- Gu Jian
- Gueye Serigne M.
- Gundell Susan M.
- Gómez-Caamaño Antonio
- Haiman Christopher A.
- Hamdy Freddie C.
- Hamilton Robert J.
- Hellwege Jacklyn N.
- Hennis Anselm J.M.
- Higashiyama Masahiko
- Hoffman Thomas J.
- Holleczek Bernd
- Hoover Robert N.
- Horvath Lisa
- Hsing Ann W.
- Hu Jennifer J.
- Huff Chad D.
- Hunter David J.
- Håkansson Niclas
- Ingles Sue A.
- Isaacs William B.
- Ito Shuji
- Jalloh Mohamed
- Jamda Mustapha A.
- Janivara Rohini
- Jenster Guido
- John Esther M.
- Joniau Steven
- Justice Amy C.
- Kachuri Linda
- Kamatani Yoichiro
- Kaneva Radka
- Keaton Jacob M.
- Kerns Sarah L.
- Key Tim J.
- Khaw Kay Tee
- Kibel Adam S.
- Kim Jeri
- Kittles Rick A.
- Klein Eric A.
- Kogevinas Manolis
- Koretsune Yukihiro
- Kote-Jarai Zsofia
- Koudou Yves Akoli
- Koutros Stella
- Kraft Peter
- Kubo Michiaki
- Kulis Tomislav
- Lachance Joseph
- Laisk Triin
- Larkin Samantha
- Leach Robin J.
- Lessel Davor
- Lim Jasmine
- Lin Daniel W.
- Lin Hui Yi
- Lindstrom Sara
- Liu Xiaoxi
- Logothetis Christopher J.
- Loos Ruth J.F.
- Lophatananon Artitaya
- Lori Adriana
- Lu Yong Jie
- Lu Zeyun
- Lubinski Jan
- Lubwama Alexander
- Luedeke Manuel
- Machiela Mitchell J.
- MacInnis Robert J.
- Madduri Ravi K.
- Maehle Lovise
- Maier Christiane
- Mancuso Nick
- Mante Sunny
- Mao Xueying
- Martin Richard M.
- Martinez Maria Elena
- Masumoto Akihide
- Matsuda Koichi
- McDonnell Shannon K.
- McKean-Cowdin Roberta
- Mcmahon Benjamin H.
- Menegaux Florence
- Mensah James E.
- Michael Agnieszka
- Minami Shiro
- Mitev Vanio
- Mohler James L.
- Momozawa Yukihide
- Morisaki Takayuki
- Mucci Lorelei A.
- Muir Kenneth
- Multigner Luc
- Murakami Yoshinori
- Murayama Shigeo
- Murphy Adam B.
- Muto Kaori
- Mägi Reedik
- Nagai Akiko
- Nagayama Satoshi
- Nakagawa Hidewaki
- Neal David E.
- Nemesure Barbara
- Neslund-Dudas Christine M.
- Neuhausen Susan L.
- Newcomb Lisa F.
- Niang Lamine
- Nielsen Sune F.
- Niwa Shelley
- Nordestgaard Borge G.
- Nordstrom Tobias
- Nwegbu Maxwell
- Obara Wataru
- Obata Daisuke
- Ogunbiyi Olufemi
- Oluwole Olabode P.
- Ost Piet
- Ostrander Elaine A.
- Ostrer Harry
- Pandha Hardev
- Parent Marie Élise
- Park Jong Y.
- Parliament Matthew
- Pashayan Nora
- Paulo Paula
- Penney Kathryn L.
- Petrovics Gyorgy
- Pilie Patrick
- Plym Anna
- Preuss Michael H.
- Razack Azad
- Rebbeck Timothy R.
- Rentsch Christopher T.
- Riboli Elio
- Risbridger Gail P.
- Rodriguez Alex A.
- Roobol Monique J.
- Rosenstein Barry S.
- Rybicki Benjamin A.
- Røder Andreas
- Sahimi Ali
- Sanderson Maureen
- Saunders Edward J.
- Schaid Daniel J.
- Schleutker Johanna
- Schnoeller Thomas
- Schöttker Ben
- Sellers Thomas A.
- Shen Jiayi
- Sheng Xin
- Shittu Olayiwola
- Singhal Sandeep
- Sinozaki Nobuaki
- Sipeky Csilla
- Slavov Chavdar
- Southey Melissa C.
- Srivastava Shiv
- Stampfer Meir
- Stanford Janet L.
- Steele Linda
- Stern Mariana C.
- Strom Sara S.
- Stroomberg Hein V.
- Sun Zan
- Suzuki Takao
- Szulkin Robert
- Sørensen Karina Dalsgaard
- Takahashi Atushi
- Takahashi Kazuhisa
- Takahashi Yasuo
- Tammela Teuvo L.J.
- Tang Wei
- Tangen Catherine M.
- Tay Evelyn
- Taylor Jack A.
- Teerlink Craig C.
- Teixeira Manuel R.
- Teo Soo Hwang
- Terao Chikashi
- Tettey Yao
- Thibodeau Stephen N.
- Thompson Ian M.
- Tilly Wayne
- Torres Mina
- Townsend Paul A.
- Travis Ruth C.
- Truelove Ann
- Truong Thérèse
- Turman Constance
- Uchio Yuji
- Usmani Nawaid
- Van den Broeck Thomas
- Van Den Eeden Stephen K.
- van Schaik Ron H.N.
- Varma Rohit
- Vega Ana
- Wan Peggy
- Wang Anqi
- Wang Ying
- Watya Stephen
- Weinstein Stephanie
- Weischer Maren
- West Catharine M.L.
- Wiklund Fredrik
- Witte John S.
- Wokolorczyk Dominika
- Wolk Alicja
- Wu Yudong
- Xu Jianfeng
- Xu Yili
- Yamaguchi Hiroki
- Yamaji Ken
- Yamanashi Yuji
- Yamoah Kosj
- Yeboah Edward D.
- Yoshimori Kozo
- Yu Yao
- Zawistowski Matthew
- Zhang Hong Wei
- Zhao Shan Chao
- Zheng Wei
- Zöllner Sebastian
- Publication venue
- Nature Research
- Publication date
- 09/11/2023
- Field of study
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups