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Atrial fibrillation and comorbidities: Clinical characteristics and antithrombotic treatment in GLORIA-AF

  • Monika Kozieł,

    Roles Conceptualization, Methodology, Writing – original draft

    Affiliations Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom, 1st Department of Cardiology and Angiology, Silesian Centre for Heart Diseases, Zabrze, Poland

  • Christine Teutsch,

    Roles Conceptualization, Investigation, Methodology, Resources, Writing – review & editing

    Affiliation Department of Clinical Development and Medical Affairs, Therapeutic Area Cardiometabolism, Boehringer Ingelheim International GmbH, Ingelheim, Germany

  • Jonathan L. Halperin,

    Roles Conceptualization, Methodology, Validation, Writing – review & editing

    Affiliation Icahn School of Medicine at Mount Sinai, New York, New York, United States of America

  • Kenneth J. Rothman,

    Roles Conceptualization, Methodology, Validation, Writing – review & editing

    Affiliation RTI Health Solutions, Research Triangle Park, North Carolina, United States of America

  • Hans-Christoph Diener,

    Roles Conceptualization, Supervision, Writing – review & editing

    Affiliation Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany

  • Chang-Sheng Ma,

    Roles Conceptualization, Writing – review & editing

    Affiliation Cardiology Department, Atrial Fibrillation Center, Beijing AnZhen Hospital, Capital Medical University, Beijing, China

  • Sabrina Marler,

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing – review & editing

    Affiliation Biostatistics and Data Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States of America

  • Shihai Lu,

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Software, Writing – review & editing

    Affiliation Biostatistics and Data Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States of America

  • Venkatesh K. Gurusamy,

    Roles Investigation, Resources, Software, Writing – review & editing

    Affiliation Global Epidemiology, Boehringer Ingelheim International GmbH, Ingelheim, Germany

  • Menno V. Huisman,

    Roles Conceptualization, Supervision, Writing – review & editing

    Affiliation Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands

  • Gregory Y. H. Lip ,

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Supervision, Validation, Writing – review & editing

    gregory.lip@liverpool.ac.uk

    Affiliations Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom, 1st Department of Cardiology and Angiology, Silesian Centre for Heart Diseases, Zabrze, Poland, Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

  • on behalf of the GLORIA-AF Investigators

    Membership of the GLORIA-AF Investigators Group is listed in the Acknowledgments.

Abstract

Background

Patients with AF often have multimorbidity (the presence of ≥2 concomitant chronic conditions).

Objective

To describe baseline characteristics, patterns of antithrombotic therapy, and factors associated with oral anticoagulant (OAC) prescription in patients with AF and ≥2 concomitant, chronic, comorbid conditions.

Methods

Phase III of the GLORIA-AF Registry enrolled consecutive patients from January 2014 through December 2016 with recently diagnosed AF and CHA2DS2-VASc score ≥1 to assess the safety and effectiveness of antithrombotic treatment.

Results

Of 21,241 eligible patients, 15,119 (71.2%) had ≥2 concomitant, chronic, comorbid conditions. The proportions of patients with multimorbidity receiving non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKA) were 60.2% and 23.6%, respectively. The proportion with paroxysmal AF was 57.0% in the NOAC group and 45.4% in the VKA group. Multivariable log-binomial regression analysis found the following factors were associated with no OAC prescription: pattern of AF (paroxysmal, persistent, or permanent), coronary artery disease, myocardial infarction, prior bleeding, smoking status, and region (Asia, North America, or Europe). Factors associated with OAC prescriptions were age, body mass index, renal function, hypertension, history of cerebral ischemic symptoms, and AF ablation.

Conclusion

Multimorbid AF patients prescribed NOACs have fewer comorbidities than those prescribed VKAs. Age, AF pattern, comorbidities, and renal function are associated with OAC prescription.

Introduction

Atrial fibrillation (AF) affects approximately 3% of adults and its prevalence and incidence are rising [1] with the aging of the population [2]. Older patients with AF often have other chronic conditions that affect their clinical course [3]. Multimorbidity (the presence of ≥2 concomitant chronic conditions) demands a holistic and integrated approach to patient care [4] since these patients face higher risks of stroke and bleeding than those without comorbidities [5, 6]. The interplay between comorbidity, AF, and optimal thromboprophylaxis has both medical and economic implications [7]

The aim of this analysis of the GLORIA-AF dataset is to describe baseline characteristics and antithrombotic therapy prescription patterns in patients with AF and multimorbidity and to identify factors associated with the selection of an oral anticoagulant (OAC) type for these complex patients.

Materials and methods

The design of the GLORIA-AF registry (https://clinicaltrials.gov/ct2/home; trial registration numbers NCT01468701, NCT01671007, NCT01937377) has been reported [8]. The study protocol is concordant with the ethical guidelines of the 1975 Declaration of Helsinki, and informed consent was obtained from each patient before enrollment.

The registry collected routine clinical practice data regarding patients with newly diagnosed AF to evaluate patient characteristics influencing the selection, safety, and effectiveness of antithrombotic therapy. Phase I was conducted before non-vitamin K antagonist oral anticoagulants (NOACs) were available for stroke prevention in AF. Phase II began when dabigatran was approved in countries with participating clinical centers. Baseline characteristics were collected and those prescribed dabigatran were followed up for 2 years in Phase II. Phase III, which started when dabigatran had been more widely adopted, gathered data for up to 3 years, regardless of antithrombotic management [8].

Consecutive patients from 38 countries were enrolled between 2014 and 2016. Adult patients with recently diagnosed nonvalvular AF (<3 months before the baseline visit; Latin America <4.5 months) at risk of stroke (CHA2DS2-VASc score ≥1) achieved by any of the following: heart failure or left ventricular systolic dysfunction, hypertension, diabetes, prior stroke, transient ischemic attack (TIA) or systemic embolism, myocardial infarction (MI), peripheral artery disease, age ≥65 years, or female sex, were enrolled [9]. The risks of stroke and bleeding were assessed using the CHA2DS2-VASc and HAS-BLED (1 point is achieved by any of the following: hypertension, abnormal renal or hepatic function, prior stroke, bleeding or predisposition, labile International Normalised Ratio, elderly [>65 years], or concomitant use of alcohol or anti-inflammatory medications) [10]. Antithrombotic therapy was prescribed by the treating physicians according to local standards. This report is focused on baseline data obtained from patients in Phase III, collected using electronic case report forms.

Statistical analysis

Baseline characteristics are summarized descriptively. Categorical variables are reported as absolute frequencies and percentages, and continuous variables are summarized by median (Quartile 1, Quartile 3). Baseline characteristics included stratification of patients with AF and multimorbidity according to stroke prevention strategies (OAC vs antiplatelet vs no antithrombotic therapy, NOAC vs vitamin K antagonists [VKAs], and NOACs once daily [QD] vs twice daily [BID]). Standardized differences were used to compare baseline characteristics across various stroke prevention strategies, focusing on variables with the highest standardized differences; differences ≤10% in absolute value were considered as balanced between groups [11].

Factors associated with antithrombotic treatment choice were analyzed by log-binomial, multivariable regression models, providing relative probability ratios for prescription (OAC vs no OAC use, NOAC vs VKA; and by region). Missing data were handled using multiple imputation, replacing missing data with multiple simulated values based on regression models to provide comparatively unbiased estimates under the missing-at-random assumption. The procedure introduces random error to compensate for the added, imputed information. The imputation regression models used 56 predictors to impute the missing data, and were repeated 20 times to give 20 datasets with imputed data [12].

Confidence intervals were calculated based on likelihood ratios and Rubin’s method to combine results across imputations. Both univariate and multivariable log-binomial regression analyses were performed to evaluate crude as well as the adjusted probability ratios together with 95% confidence intervals. The term “probability ratio” was used rather than “risk ratio”, as our measure describes treatment selections rather than adverse outcomes.

All data were calculated using SAS version 9.4 (SAS Institute, Inc., Cary, NC).

Results

Of 21,241 eligible patients in this subanalysis, 15,119 (71.2%) had ≥2 concomitant, chronic conditions (Table 1).

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Table 1. Proportion of AF patients according to number of comorbid diseasesa.

https://doi.org/10.1371/journal.pone.0249524.t001

Baseline characteristics of AF multimorbid patients

Baseline characteristics of patients are summarized based on antithrombotic therapy (Table 2). Among multimorbid AF patients, 83.8% were prescribed OACs, 11.0% were prescribed antiplatelet therapy, and 5.2% were prescribed no antithrombotic therapy. The median (66.0, 79.0) age was 73.0 years in the OAC group, 71.0 (63.0–79.0) years in the antiplatelet therapy group, and 72.0 (64.0–80.0) years in the no antithrombotic therapy group. The proportions of females in these groups were 44.5%, 41.7%, and 45.5%, respectively. The median CHA2DS2-VASc and HAS-BLED scores were similar across the 3 groups.

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Table 2. Baseline characteristics of AF multimorbid patients prescribed OAC or antiplatelets or no antithrombotic therapya.

https://doi.org/10.1371/journal.pone.0249524.t002

Baseline characteristics of patients prescribed NOACs or VKAs are shown in Table 3. The median age was 73.0 (66.0–79.0) years, and the proportion of females was 44% in both treatment groups. There were no differences in CHA2DS2-VASc and HAS-BLED scores between these 2 groups. The prevalence of paroxysmal AF in patients with multimorbidity on NOACs and VKAs was 57.0% and 45.4%, respectively. Among patients on NOACs, 38.4% had a European Heart Rhythm Association symptom score of I, compared with 33.3% for patients on VKAs. A lower proportion (1.6%) of patients on NOACs had a glomerular filtration rate of 15–29 mL/min, compared with 4.4% of those on VKAs.

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Table 3. Baseline characteristics of AF multimorbid patients prescribed NOACs or VKAsa.

https://doi.org/10.1371/journal.pone.0249524.t003

Cardioversion was performed in 19.9% of patients on NOACs vs 14.6% of those on VKAs. Treatment in specialist offices was more prevalent for patients on NOACs (33.5% vs 23.8% in the VKA group), while comorbidities such as heart failure (HF) and MI were less prevalent among patients given NOACs.

Patient demographics, cardiovascular risk factors, comorbid diseases, AF categorization, stroke and bleeding risks, and concomitant treatments of patients on NOACs QD vs BID are summarized in Table 4 There were generally small differences between patients taking NOACs QD vs BID. Previous TIA or stroke were present in 14.9% of the patients on NOACs QD vs 21.3% of the patients on NOACs BID (Table 4).

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Table 4. Baseline characteristics of AF multimorbid patients prescribed NOACs QD or NOACs BID.

https://doi.org/10.1371/journal.pone.0249524.t004

Factors associated with OAC non-prescription in multimorbid AF patients globally

Results from univariate analyses are presented in the S1 File. In the multivariable log-binomial regression analysis, factors associated with prescriptions for no OAC use in multimorbid AF patients were: type of AF (paroxysmal/persistent vs permanent), coronary artery disease (CAD), MI, history of bleeding, smoking status (current vs nonsmoker), and region (Asia, North America vs Europe). Factors associated with increased OAC use were: age 65–74 vs ≥75 years, body mass index (BMI) class (≥25 vs 18.5–24 kg/m2), creatinine clearance (30–59 vs ≥80 mL/min), hypertension, prior TIA or stroke, and AF ablation (Table 5).

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Table 5. Multivariable log-binomial analysis for factors associated with prescription of OAC therapy (no OAC vs OAC)a,b.

https://doi.org/10.1371/journal.pone.0249524.t005

Factors associated with OACs non-prescription in multimorbid AF patients in Asia, Europe, and North America

Factors associated with prescriptions for no OAC use in multimorbid AF patients in Asia, Europe, and North America are presented in S1 Table in S2 File. Factors associated with increased OAC use are included in S1 Table in S2 File.

Factors associated with type of OAC use in multimorbid AF patients globally

Factors associated with prescriptions for VKA use globally in multimorbid AF patients were: age <75 vs ≥75 years, MI, congestive HF, diabetes mellitus, creatinine clearance (<60 vs ≥80 mL/min), S2 Table in S2 File.

Factors associated with decreased VKA use globally were: type of AF (paroxysmal/persistent vs permanent), previous TIA or stroke, medical treatment reimbursement (self-pay/no coverage vs not self-pay), S2 Table in S2 File.

Factors associated with OAC use in multimorbid AF patients in Asia, Europe, North America, and Latin America

Factors associated with prescriptions for VKA use in multimorbid AF patients in Asia, Europe, North America, and Latin America are presented in S3 Table in S2 File. Factors associated with decreased prescriptions for VKA use in multimorbid AF patients in Asia, Europe, North America, and Latin America are presented in S3 Table in S2 File.

Discussion

There are still knowledge gaps in how OACs are used in clinical practice in patients with AF and multiple comorbidities and which factors influence OAC prescription in such patients. Our study shows that, despite a median CHA2DS2-VASc score >3, approximately 16% of patients with multimorbidity and AF are not anticoagulated. The baseline characteristics in these complex patients differ in relation to antithrombotic therapy selection, suggesting that comorbidities may influence antithrombotic therapy prescription patterns for patients with AF. For example, prescription of OACs globally in patients with AF and multimorbidity was associated with age, BMI, cardiovascular risk factors (smoking status), AF pattern, concomitant diseases (ie, hypertension, CAD, MI, previous TIA or stroke), history of bleeding, renal function, rhythm control strategy (AF ablation and AF cardioversion), and region (Asia and North America). Prescriptions patterns were also subject to regional differences in clinical practice.

Patient characteristics according to antithrombotic therapy use

The results suggest that patients with AF and multimorbidity prescribed NOACs are more likely to have paroxysmal AF, and have fewer comorbidities than those prescribed VKAs, consistent with other reports [1315]. Declining renal function may influence the choice of VKA in those with chronic kidney disease. Healthcare system-related factors (such as center type) also influence treatment strategies. Patients with AF and multimorbidity treated in specialist offices and community hospitals are more often prescribed NOACs than VKAs.

The patients in this cohort prescribed antiplatelet agents had a higher risk of bleeding according to HAS-BLED score than those who were prescribed OACs. They also more often had paroxysmal AF compared to those prescribed OACs. Patients with AF and CAD were more often prescribed antiplatelets than OACs despite the fact that antiplatelet therapy does not prevent stroke or reduce mortality, elevates the risk of bleeding, and is not recommended for prevention of AF-related thromboembolism [16]. Unfortunately, antiplatelet monotherapy is still a frequent choice of prescribing physicians based on several European reports [17, 18].

Factors associated with OAC prescription in multimorbid AF patients globally

The majority of multimorbid AF patients had a high risk of stroke (CHA2DS2-VASc score ≥2) and oral anticoagulation therapy is recommended for these patients [19]. Hypertension and HF were the most prevalent risk factors for thromboembolic complications [20] and these factors and previous stroke or TIA are associated with a greater frequency of OAC prescription. Prescription of OACs was inversely associated with comorbidities that are strongly associated with elevated thromboembolic risk (eg, MI, CAD), just as conditions associated with an increased risk of bleeding (eg, previous hemorrhagic events) were associated with less frequent prescription of OACs. This is also consistent with prior reports [13] although current clinical practice guidelines recommend that patients with AF at a high risk of bleeding should generally continue anticoagulation with frequent visits and close monitoring [21]. A history of AF ablation in multimorbid AF patients was associated with more frequent OAC prescription as per guidelines [21] and consistent with other studies [22].

Younger age (≤75 years) was associated with greater OAC prescription and more frequent selection of VKAs compared to practice patterns for older patients. Several studies have suggested that increasing age is a barrier to implementing OAC use [23, 24]. Importantly, stroke risk increases with age, and the absolute benefit of OACs is clearly increased for older patients with AF [25]. In one report, when adjusted for comorbidity, age was not an important determinant of anticoagulation [26].

Multimorbid AF patients with paroxysmal or persistent AF were less often prescribed OACs in particular VKAs than those with permanent AF. NOACs should be preferred in patients with multimorbidity and polypharmacy given their lower number of drug–drug interactions compared with VKAs [27]. Ischemic stroke may occur as frequently in paroxysmal AF as in permanent AF, especially with multiple risk factors [28]. Moreover, the use of OACs should be based on stroke risk assessment according to the CHA2DS2-VASc risk score [21]. The pattern of AF seems to be related to patient profiles characterized by age, concomitant diseases, symptoms, and risk factors for stroke and bleeding [13]. Patients with higher European Heart Rhythm Association symptom scores were more often prescribed VKAs than those who were asymptomatic.

Multimorbid AF patients with a history of cardioversion were less often prescribed VKAs than those without prior cardioversion. NOACs were preferred in multimorbid AF patients after cardioversion. A similar pattern was found in another study where rhythm control strategy was associated with selection of NOAC [14].

OAC prescription in multimorbid AF patients regionally

In this study, multimorbidity influenced ATT use within particular regions. In Europe, younger patients (age <65 years) were less likely to be prescribed OACs than older patients (age ≥75 years). Multimorbid AF patients with congestive HF were more likely to be anticoagulated due to an increased risk of thromboembolism. In Europe, bleeding risk of a patient as perceived by physicians may be the reason for decreased use of anticoagulation. Patients with gastritis or duodenitis or hepatic disease are less likely to be prescribed OACs, probably because of the elevated risk of bleeding. This association has been previously noted [26]. In Asia, younger patients (age <75 years) were more likely to be prescribed OACs than older patients (age ≥75 years). Interestingly, patients with gastritis or duodenitis or a history of cancer were more likely to receive OAC than those without those diseases. In North America, younger multimorbid AF patients (age <65 years) were less likely to be prescribed OACs than older patients (age ≥75 years). Multimorbid AF patients with diabetes were more likely to receive OACs, due to their association with higher thromboembolic risk, as well as higher all-cause, cardiovascular, and noncardiovascular mortality [29]. AF patients with multimorbidity and cancer in North America were less likely to receive OAC.

Asia and North America were associated with decreased OAC prescription. In Asia, OACs are less commonly prescribed in nonvalvular AF patients than in Europe, possibly because of suspicion of the risk of bleeding during treatment [30]. Also, NOACs are not reimbursed in some Asian countries.

Strengths

It is one the largest prospective global cohort of consecutive AF patients receiving different antithrombotic treatments. Initiation of Phase III was region-specific, once relevant baseline characteristics of patients initiating dabigatran and VKA therapy in Phase II overlapped based on propensity score comparisons. After the baseline visit, all patients in this Phase III were managed according to local clinical practice and were followed for 3 years, regardless of prescribed antithrombotic therapy. This study had regular follow-up with physicians, alongside on-site monitoring, multiple standards for data quality assurance and review.

Limitations

Although the GLORIA-AF study was designed to capture all outcome events, this analysis did not consider follow-up data. The following limitations exist in our study: we have no data on patient and prescriber treatment preferences; similarly, reasons for OAC nonprescription were not reported. Furthermore, this study reflects single, initial-treatment decisions during a period when prescribing patterns may have been changing, and the analysis was based on prescription pattern shortly after entry into the registry (baseline). Neither have we accounted for quality of anticoagulation or changes in clinical practice patterns over time.

Conclusion

AF patients with multimorbidity who were prescribed NOACs were relatively healthier, more likely to have paroxysmal AF, and had fewer prevalent comorbidities than AF multimorbid patients on VKAs. Multimorbidity may determine the antithrombotic therapy prescription pattern within AF patients. Several factors are related to increased OAC prescription in multimorbid AF patients, including younger age, hypertension, prior TIA or stroke, and AF ablation. Pattern of AF (paroxysmal and persistent AF), CAD, MI, history of bleeding, and region (Asia, North America) were inversely associated with OAC prescription.

Acknowledgments

The authors thank the patients who participated in this trial, their families, the investigators, study co-ordinators, and study teams.

GLORIA_AF Phase III Participating Investigator listing.

Dzifa Wosornu Abban

Nasser Abdul

Atilio Marcelo Abud

Fran Adams

Srinivas Addala

Pedro Adragão

Walter Ageno

Rajesh Aggarwal

Sergio Agosti

Piergiuseppe Agostoni

Francisco Aguilar

Julio Aguilar Linares

Luis Aguinaga

Jameel Ahmed

Allessandro Aiello

Paul Ainsworth

Jorge Roberto Aiub

Raed Al-Dallow

Lisa Alderson

Jorge Antonio Aldrete Velasco

Dimitrios Alexopoulos

Fernando Alfonso Manterola

Pareed Aliyar

David Alonso

Fernando Augusto Alves da Costa

José Amado

Walid Amara

Mathieu Amelot

Nima Amjadi

Fabrizio Ammirati

Marianna Andrade

Nabil Andrawis

Giorgio Annoni

Gerardo Ansalone

M.Kevin Ariani

Juan Carlos Arias

Sébastien Armero

Chander Arora

Muhammad Shakil Aslam

M. Asselman

Philippe Audouin

Charles Augenbraun

S. Aydin

Ivaneta Ayryanova

Emad Aziz

Luciano Marcelo Backes

E. Badings

Ermentina Bagni

Seth H. Baker

Richard Bala

Antonio Baldi

Shigenobu Bando

Subhash Banerjee

Alan Bank

Gonzalo Barón Esquivias

Craig Barr

Maria Bartlett

Vanja Basic Kes

Giovanni Baula

Steffen Behrens

Alan Bell

Raffaella Benedetti

Juan Benezet Mazuecos

Bouziane Benhalima

Jutta Bergler-Klein

Jean-Baptiste Berneau

Richard A. Bernstein

Percy Berrospi

Sergio Berti

Andrea Berz

Elizabeth Best

Paulo Bettencourt

Robert Betzu

Ravi Bhagwat

Luna Bhatta

Francesco Biscione

Giovanni BISIGNANI

Toby Black

Michael J. Bloch

Stephen Bloom

Edwin Blumberg

Mario Bo

Ellen Bøhmer

Andreas Bollmann

Maria Grazia Bongiorni

Giuseppe Boriani

D.J. Boswijk

Jochen Bott

Edo Bottacchi

Marica Bracic Kalan

Drew Bradman

Donald Brautigam

Nicolas Breton

P.J.A.M. Brouwers

Kevin Browne

Jordi Bruguera Cortada

A. Bruni

Claude Brunschwig

Hervé Buathier

Aurélie Buhl

John Bullinga

Jose Walter Cabrera

Alberto Caccavo

Shanglang Cai

Sarah Caine

Leonardo Calò

Valeria Calvi

Mauricio Camarillo Sánchez

Rui Candeias

Vincenzo Capuano

Alessandro Capucci

Ronald Caputo

Tatiana Cárdenas Rizo

Francisco Cardona

Francisco Carlos da Costa Darrieux

Yan Carlos Duarte Vera

Antonio Carolei

Susana Carreño

Paula Carvalho

Susanna Cary

Gavino Casu

Claudio Cavallini

Guillaume Cayla

Aldo Celentano

Tae-Joon Cha

Kwang Soo Cha

Jei Keon Chae

Kathrine Chalamidas

Krishnan Challappa

Sunil Prakash Chand

Harinath Chandrashekar

Ludovic Chartier

Kausik Chatterjee

Carlos Antero Chavez Ayala

Aamir Cheema

Amjad Cheema

Lin Chen

Shih-Ann Chen

Jyh Hong Chen

Fu-Tien Chiang

Francesco Chiarella

Lin Chih-Chan

Yong Keun Cho

Jong-Il Choi

Dong Ju Choi

Guy Chouinard

Danny Hoi-Fan Chow

Dimitrios Chrysos

Galina Chumakova

Eduardo Julián José Roberto Chuquiure Valenzuela

Nicoleta Cindea Nica

David J. Cislowski

Anthony Clay

Piers Clifford

Andrew Cohen

Michael Cohen

Serge Cohen

Furio Colivicchi

Ronan Collins

Paolo Colonna

Steve Compton

Derek Connolly

Alberto Conti

Gabriel Contreras Buenostro

Gregg Coodley

Martin Cooper

Julian Coronel

Giovanni Corso

Juan Cosín Sales

Yves Cottin

John Covalesky

Aurel Cracan

Filippo Crea

Peter Crean

James Crenshaw

Tina Cullen

Harald Darius

Patrick Dary

Olivier Dascotte

Ira Dauber

Vicente Davalos

Ruth Davies

Gershan Davis

Jean-Marc Davy

Mark Dayer

Marzia De Biasio

Silvana De Bonis

Raffaele De Caterina

Teresiano De Franceschi

J.R. de Groot

José De Horta

Axel De La Briolle

Gilberto de la Pena Topete

Angelo Amato Vicenzo de Paola

Weimar de Souza

A. de Veer

Luc De Wolf

Eric Decoulx

Sasalu Deepak

Pascal Defaye

Freddy Del-Carpio Munoz

Diana Delic Brkljacic

N. Joseph Deumite

Silvia Di Legge

Igor Diemberger

Denise Dietz

Pedro Dionísio

Qiang Dong

Fabio Rossi dos Santos

Elena Dotcheva

Rami Doukky

Anthony D’Souza

Simon Dubrey

Xavier Ducrocq

Dmitry Dupljakov

Mauricio Duque

Dipankar Dutta

Nathalie Duvilla

A. Duygun

Rainer Dziewas

Charles B. Eaton

William Eaves

L.A Ebels-Tuinbeek

Clifford Ehrlich

Sabine Eichinger-Hasenauer

Steven J. Eisenberg

Adnan El Jabali

Mahfouz El Shahawy

Mauro Esteves Hernandes

Ana Etxeberria Izal

Rudolph Evonich III

Oksana Evseeva

Andrey Ezhov

Raed Fahmy

Quan Fang

Ramin Farsad

Laurent Fauchier

Stefano Favale

Maxime Fayard

Jose Luis Fedele

Francesco Fedele

Olga Fedorishina

Steven R. Fera

Luis Gustavo Gomes Ferreira

Jorge Ferreira

Claudio Ferri

Anna Ferrier

Hugo Ferro

Alexandra Finsen

Brian First

Stuart Fischer

Catarina Fonseca

Luísa Fonseca Almeida

Steven Forman

Brad Frandsen

William French

Keith Friedman

Athena Friese

Ana Gabriela Fruntelata

Shigeru Fujii

Stefano Fumagalli

Marta Fundamenski

Yutaka Furukawa

Matthias Gabelmann

Nashwa Gabra

Niels Gadsbøll

Michel Galinier

Anders Gammelgaard

Priya Ganeshkumar

Christopher Gans

Antonio Garcia Quintana

Olivier Gartenlaub

Achille Gaspardone

Conrad Genz

Frédéric Georger

Jean-Louis Georges

Steven Georgeson

Evaldas Giedrimas

Mariusz Gierba

Ignacio Gil Ortega

Eve Gillespie

Alberto Giniger

Michael C. Giudici

Alexandros Gkotsis

Taya V. Glotzer

Joachim Gmehling

Jacek Gniot

Peter Goethals

Seth Goldbarg

Ronald Goldberg

Britta Goldmann

Sergey Golitsyn

Silvia Gómez

Juan Gomez Mesa

Vicente Bertomeu Gonzalez

Jesus Antonio Gonzalez Hermosillo

Víctor Manuel González López

Hervé Gorka

Charles Gornick

Diana Gorog

Venkat Gottipaty

Pascal Goube

Ioannis Goudevenos

Brett Graham

G. Stephen Greer

Uwe Gremmler

Paul G. Grena

Martin Grond

Edoardo Gronda

Gerian Grönefeld

Xiang Gu

Ivett Guadalupe Torres Torres

Gabriele Guardigli

Carolina Guevara

Alexandre Guignier

Michele Gulizia

Michael Gumbley

Albrecht Günther

Andrew Ha

Georgios Hahalis

Joseph Hakas

Christian Hall

Bing Han

Seongwook Han

Joe Hargrove

David Hargroves

Kenneth B. Harris

Tetsuya Haruna

Emil Hayek

Jeff Healey

Steven Hearne

Michael Heffernan

Geir Heggelund

J.A. Heijmeriks

Maarten Hemels

I. Hendriks

Sam Henein

Sung-Ho Her

Paul Hermany

Jorge Eduardo Hernández Del Río

Yorihiko Higashino

Michael Hill

Tetsuo Hisadome

Eiji Hishida

Etienne Hoffer

Matthew Hoghton

Kui Hong

Suk keun Hong

Stevie Horbach

Masataka Horiuchi

Yinglong Hou

Jeff Hsing

Chi-Hung Huang

David Huckins

kathy Hughes

A. Huizinga

E.L. Hulsman

Kuo-Chun Hung

Gyo-Seung Hwang

Margaret Ikpoh

Davide Imberti

Hüseyin Ince

Ciro Indolfi

Shujiro Inoue

Didier Irles

Harukazu Iseki

C. Noah Israel

Bruce Iteld

Venkat Iyer

Ewart Jackson-Voyzey

Naseem Jaffrani

Frank Jäger

Martin James

Sung-Won Jang

Nicolas Jaramillo

Nabil Jarmukli

Robert J. Jeanfreau

Ronald D. Jenkins

Carlos Jerjes Sánchez

Javier Jimenez

Robert Jobe

Tomas Joen-Jakobsen

Nicholas Jones

Jose Carlos Moura Jorge

Bernard Jouve

Byung Chun Jung

Kyung Tae Jung

Werner Jung

Mikhail Kachkovskiy

Krystallenia Kafkala

Larisa Kalinina

Bernd Kallmünzer

Farzan Kamali

Takehiro Kamo

Priit Kampus

Hisham Kashou

Andreas Kastrup

Apostolos Katsivas

Elizabeth Kaufman

Kazuya Kawai

Kenji Kawajiri

John F. Kazmierski

P Keeling

José Francisco Kerr Saraiva

Galina Ketova

AJIT Singh Khaira

Aleksey Khripun

Doo-Il Kim

Young Hoon Kim

Nam Ho Kim

Dae Kyeong Kim

Jeong Su Kim

June Soo Kim

Ki Seok Kim

Jin bae Kim

Elena Kinova

Alexander Klein

James J. Kmetzo

G. Larsen Kneller

Aleksandar Knezevic

Su Mei Angela Koh

Shunichi Koide

Athanasios Kollias

J.A. Kooistra

Jay Koons

Martin Koschutnik

William J. Kostis

Dragan Kovacic

Jacek Kowalczyk

Natalya Koziolova

Peter Kraft

Johannes A. Kragten

Mori Krantz

Lars Krause

B.J. Krenning

F. Krikke

Z. Kromhout

Waldemar Krysiak

Priya Kumar

Thomas Kümler

Malte Kuniss

Jen-Yuan Kuo

Achim Küppers

Karla Kurrelmeyer

Choong Hwan Kwak

Bénédicte Laboulle

Arthur Labovitz

Wen Ter Lai

Andy Lam

Yat Yin Lam

Fernando Lanas Zanetti

Charles Landau

Giancarlo Landini

Estêvão Lanna Figueiredo

Torben Larsen

Karine Lavandier

Jessica LeBlanc

Moon Hyoung Lee

Chang-Hoon Lee

John Lehman

Ana Leitão

Nicolas Lellouche

Malgorzata Lelonek

Radoslaw Lenarczyk

T. Lenderink

Salvador León González

Peter Leong-Sit

Matthias Leschke

Nicolas Ley

Zhanquan Li

Xiaodong Li

Weihua Li

Xiaoming Li

Christhoh Lichy

Ira Lieber

Ramon Horacio Limon Rodriguez

Hailong Lin

Gregory Y. H. Lip

Feng Liu

Hengliang Liu

Guillermo Llamas Esperon

Nassip Llerena Navarro

Eric Lo

Sergiy Lokshyn

Amador López

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Ming Luo

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Genshan Ma

Irene Madariaga

Koji Maeno

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Gustavo Maid

Sumeet K. Mainigi

Konstantinos Makaritsis

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Rickey Manning

Athanasios Manolis

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Ioannis Mantas

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Niccolo Marchionni

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Petra Maskova

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Hiroshi Meno

Dhananjai Menzies

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Thuraia Nageh

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Ole Nyvad

Manuel Odin de Los Rios Ibarra

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eena Padayattil jose

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Alessandro Salvioni

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Wenxia Zong

L Steven Zukerman

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