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Atherosclerosis 204 (2009) e86–e92
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Atherosclerosis
journal homepage: www.elsevier.com/locate/atherosclerosis
Cardiovascular risk factor control and outcomes in peripheral artery disease
patients in the Reduction of Atherothrombosis for Continued Health (REACH)
Registry
Patrice P. Cacoub a,∗ ,Maria Teresa B. Abola b ,Iris Baumgartner c ,Deepak L. Bhatt d ,
Mark A.Creager e ,Chiau-Suong Liau f ,Shinya Goto g ,Joachim Röther h ,
P. Gabriel Steg i ,Alan T. Hirsch j ,onbehalf of the REACH Registry Investigators
a Pierre and Marie Curie University-Paris 6, and AP HP, Hospital La Pitié-Salpêtrière, Paris, France
b Vascular Medicine Section, Division of Clinical Cardiology, Department of Cardiovascular Medicine, Philippine Heart Center, Quezon City, Philippines
c Clinical and Interventional Angiology, Swiss Cardiovascular Centre, University Hospital, Bern, Switzerland
d VA Boston Healthcare FOR
System and Brigham and Women’s ELECTRONIC
Hospital, Boston, MA, USA
e Brigham and and Women’s Hospital, Harvard Medical School, Boston, MA, USA
f National Taiwan University Hospital and School of Medicine, Taipei, Taiwan
g Tokai University, Isehara, Japan
h Klinikum Minden, Hannover Medical School, Minden, Germany
i INSERM U-698 et Université Paris VII–Denis Diderot, Hôpital Bichat-Claude Bernard, Paris, France
j Vascular Medicine Program, Division of Epidemiology and Community Health, University of Minnesota
School of Public Health and Minneapolis Heart Institute Foundation, MN, USA
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abstract
Article history:
Received 25July 2008
Received inrevised form 8October 2008
Accepted 9October 2008
Available online 31 October 2008
Keywords:
Peripheral artery disease
Risk factor control
Cardiovascular events
Cohort study
REACH Registry
1. Introduction
Peripheral arterydisease (PAD) is aprevalent atherothrombotic
syndrome that most commonly affects people >60 years. As populations
age, the prevalence of PAD and its associated adverse
outcomes will also increase.
∗ Corresponding author.Service de Médecine Interne, Groupe Hospitalier La Pitié-
Salpêtrière, 47-83, Boulevard de l’Hôpital, 75013 Paris, France. Tel.: +33142 178009;
fax: +33 142 178033.
E-mail address: patrice.cacoub@psl.aphp.fr (P.P. Cacoub).
0021-9150/$ –see front matter ©2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.atherosclerosis.2008.10.023
Objectives: To examine differences in risk factor (RF) management between peripheral arterydisease (PAD)
and coronaryartery(CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major
1-year cardiovascular (CV) event rates.
Methods: The REACH Registryrecruited >68000 outpatients aged ≥45 years with establishedatherothrombotic
disease or ≥3 RFs for atherothrombosis. The predictors of RF control that were evaluated included:
(1) patient demographics, (2) mode of PADdiagnosis, and (3) concomitant CAD and/or CVD.
Results: RF control was less frequent in patients with PAD (n=8322), compared with those with CAD
or CVD (but no PAD, n =47492) [blood pressure; glycemia; total cholesterol; smoking cessation (each
P

The Reduction of Atherothrombosis for ContinuedHealth (REACH)
Registry was initiated to evaluate outpatients who would represent
the entire spectrum of atherothrombotic clinical syndromes,
from the mostgeographicallyand ethnicallydiverse population yet
surveyed.
The REACH Registry provided aunique opportunity to analyze
aglobal atherothrombotic population. We assessedaseries of predictors
of RF control and examined the differences in risk factor
management intensity between PAD and CAD orcerebrovascular
disease (CVD). Furthermore, we evaluated predictors of risk factor
management in PAD.
2. Methods
The REACH Registry isaninternational, prospective, observationalregistrywith
up to 4years of clinical follow-up. The Registry
design has been published elsewhere [11]. Briefly, consecutive eligible
outpatients aged 45 years or older with establishedCAD, CVD
or PAD, or with ≥3 atherothrombotic RFs were enrolled worldwide
over an initial seven-month recruitment period (December
2003–June 2004).
Selection of physicians to the REACH Registry was determined
at the country level. To ensure homogeneity and agood represen- represen-
tation inthe in the REACH Registry population, asite selection method
was designed and implemented in each participating country
by epidemiologists under the supervision of the REACH Registry
global and local steering committees and national coordinators.
The site selection method took into account various and com-
plex criteria such aspatient profiles (e.g., CAD, CVD, or PAD, or
risk of atherothrombotic events), physician profiles (e.g., general
practitioners, internists, cardiologists, neurologists), healthcare
environments (rural, suburban, urban), and medical practices
(office-based, hospital-based). This selection was designed totry
to mimic the best available epidemiological data in each country
that reflect the burden of atherothrombosis or at-risk populations.
The national coordinator in each country made the final decision
on the selection of physicians and sites in each country.
For the present study, weanalyzed data from patients with
established atherothrombotic disease (PAD, CAD or CVD), documented
by medical records (documented CAD, ≥1 of: stable
angina with documented CAD, history of unstable angina with
documented CAD, history of percutaneous coronary intervention
(PCI) or coronary artery bypass graft (CABG) surgery, orprevious
myocardial infarction (MI); CVD, ahospital or neurologist report
diagnosing transient ischemic attack(TIA) or ischemic stroke;PAD,
current intermittent claudication with an ABI of less than 0.9 and/or
ahistory of intermittent claudication together with aprevious
lower extremity procedure).
Patients already in a clinical trial, hospitalized patients, or
those who might have difficulty returning for afollow-up visit
were excluded from enrolment. The protocol was submitted to
the institutional review board ineach country according to local
requirements, and signed, informed consent was obtained for
all patients. Family practitioners and general practitioners (44%
of the physicians) as well as other office-based specialists in
areas such as internal medicine (29%), cardiology (13%), neurology
(9%), endocrinology (2%), general surgery (2%), vascular
disease (1%), and other fields (1%) recruited amaximum of 15
patients (or 20 in the United States) into the study. Data were
collected centrally using astandardized international case report
form that was completed atthe study visit. Baseline seated systolic
blood pressure (SBP) and diastolic blood pressure (DBP), and
available fasting glucose and cholesterol levels were obtained.
Current smoking was defined as ≥5 cigarettes/day on average
P.P. Cacoub et al. /Atherosclerosis 204 (2009) e86–e92 e87
within the last month before study entry; former smoking was
defined as≥5cigarettes/day onaverage more than one month
before study entry. Polyvascular disease was defined ascoexistent
symptomatic (clinically recognized) arterial disease in two or
three territories (coronary, cerebral, and/or peripheral) within each
patient.
2.1. Definition of RF control
RFs were includedifdocumented in the subject’s medical record
or if the subject was receiving RF treatment at the time of study
enrolment. Evidence of aRFwas evaluated at baseline. Thereafter,
we categorizedeachRFas‘controlled’ if theywereatthe targetgoal
of the international guideline recommendations [12–14] (including
SBP

e88 P.P. Cacoub et al. /Atherosclerosis 204 (2009) e86–e92
Table 1
Baseline demographic characteristics, geographic regions and concomitant illnesses for patients included inthe REACH Registry with or without PAD.
Age (years), mean (SD) Patients with PAD n =8322 (14.9%) Patients without PAD n =47492 (85.1%) Total n =55814 P-value *
Sex ratio (M/F) 69.3 (9.9) 68.3 (10.2) 68.5 (10.1)

Table 2
CV risk factors controlled and at target inpatients with or without PADinthe REACH Registry.
P.P. Cacoub et al. /Atherosclerosis 204 (2009) e86–e92 e89
Number of risk factors controlled a Patients with PAD Patients without PAD P-value *
n =8322 % b n =47492 % b

e90 P.P. Cacoub et al. /Atherosclerosis 204 (2009) e86–e92
Table 4
One year follow-up event rates a for patients with PAD whether isolated (PAD only group) or associated with concomitant CAD orCVD (polyvascular disease group) as a
function of the number of cardiovascular risk factors at the target atbaseline.
One year follow-up (%) PADonly PAD plus polyvascular disease
Poor control (0–2 RFs Good control (3–5 RFs P-value Poor control (0–2 RFs Good control (3–5 RFs
controlled)
controlled)
controlled)
controlled)
Frequency 1694 1373 2124 2720
Major CV events
Non-fatal MI 1.15 [0.34; 1.96] 0.87 [0.20; 1.54] 0.5269 2.03 [1.14; 2.91] 1.29 [0.70; 1.88] 0.1475
Non-fatal stroke 1.07 [0.29; 1.84] 0.47 [0.03; 0.92] 0.1530 3.36 [2.17;4.55] 1.87 [1.14; 2.61] 0.0054
CV death 1.46 [0.61; 2.30] 1.42 [0.48; 2.36] 0.6238 3.19 [2.10;4.26] 3.74 [2.65; 4.81] 0.2005
MI/stroke/CV death 3.52 [2.16;4.86] 2.66 [1.45; 3.86] 0.1676 7.73 [6.05; 9.38] 6.48 [5.12; 7.82] 0.2690
MI/stroke/CV death +hosp 18.37 [15.85; 20.82] 17.65 [14.99; 20.22] 0.8123 26.43 [24.05; 28.73] 23.16 [21.04; 25.22] 0.0866
Total mortality 2.22 [1.20; 3.22] 2.74 [1.44; 4.01] 0.5960 4.53 [3.24; 5.79] 5.31 [4.03; 6.57] 0.1135
Progression of PAD
Worsening of claudication 16.54 [14.10;18.90] 17.08 [14.42; 19.65] 0.6021 17.58 [15.43; 19.69] 15.66 [13.76; 17.52] 0.2175
Angioplasty/stent for PAD 5.26 [3.76; 6.73] 6.59 [4.73; 8.42] 0.1219 4.93 [3.67; 6.18] 5.16 [3.94; 6.37] 0.6173
Peripheral bypass surgery 4.84 [3.35; 6.32] 4.55 [3.04; 6.04] 0.7574 3.64 [2.53; 4.74] 3.40 [2.41; 4.38] 0.7294
Amputation 1.98 [1.02; 2.93] 2.26 [1.14; 3.36] 0.6198 1.77 [0.96; 2.57] 1.34 [0.74; 1.94] 0.2729
a Presented as event rates [95% CIs]. CV =cardiovascular; MI=myocardial infarction; PAD=peripheral artery disease.
PAD only patients and polyvascular PAD patients had fewer reasons to account for undertreatment of atherothrombotic RFs in
major CV events in association with good RF control. However, PADpatients. One is the lowperception of risk associated with PAD
statistical significance
FOR
wasonlyreachedfor non-fatal
ELECTRONIC
stroke in poly- poly- compared with that associated with CAD orCVD. AUSnational
vascular PADpatient group (P ( P =0.005).
survey study reported alack ofphysician knowledge and attitudes
The rate of major CV events increased step-wise from patients regarding the importance of atherothrombotic RF treatment in PAD
with PADonly, to patients with CAD orCVD without PAD, and was patients [19]. [19].Insufficient Insufficient awareness by PADpatients of the risksof
highestinpolyvascular patients (PAD and CAD ± CVD). Forexample, CV events and the importance of RF treatment influences lowrates
the annual rate of CV death was 1.4%, 1.7% and 3.3%, respec- of RF control [20]. In addition, patient-targeted healthcare cam-
tively,
DISTRIBUTION
inthese three groups (P ( P

Prof. Cacoub has received research grants from sanofi-aventis,
Schering Plough, Servier, Roche, Encysive and Gilead; honoraria
from sanofi-aventis, Schering Plough, Servier, Roche, Encysive,
Gilead, AstraZeneca, and Bristol-Myers Squibb.
Dr. Abola has received honoraria from sanofi-aventis, Pfizer,
Otsuka and Bayer; amember of an advisory board sponsored by
sanofi-aventis and has received study grants from AstraZeneca,
Boehringer-Ingelheim, Mayer, MSD, Otsuka, Pfizer, sanofi-aventis
and Servier.
Prof. Baumgartner: None declared.
Dr.Bhatt discloses the following relationships: Research Grants
(directly tothe institution) –Bristol-Myers Squibb, Eisai, Ethicon,
sanofi-aventis, The Medicines Company; Honoraria (donated to
non-profits for >2years) –Astra Zeneca, Bristol-Myers Squibb,
Centocor, Daiichi-Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Millennium,
Paringenix, PDL, sanofi-aventis, Schering Plough, The
Medicines Company, tns Healthcare; Speaker’s bureau (>2 years
ago)–Bristol-Myers Squibb, sanofi-aventis, The Medicines Company;
Consultant/Advisory Board (any honoraria donated to
non-profits) –Astra Zeneca, Bristol-Myers Squibb, Cardax, Centocor,
Cogentus, Daiichi-Sankyo, Eisai, Eli Lilly, GlaxoSmithKline,
Johnson &Johnson, McNeil, Medtronic, Millennium, Otsuka, Paringenix,
PDL, Philips, Portola, sanofi-aventis, Schering Plough, The
Medicines Company, tns Healthcare, Vertex; Expert testimony
regarding clopidogrel (the compensation was donated to anonprofit
organization); Cleveland Clinic Coordinating Center currently
receives or has received research funding from: Abraxis, Alex-
P.P. Cacoub et al. /Atherosclerosis 204 (2009) e86–e92 e91
if they were atthe target ofthe international guideline recomion Pharma, AstraZeneca, Atherogenics, Aventis, Biosense Webster,
mendations, regardless of whether patients received aspecific RF Biosite, Boehringer Ingelheim, Boston Scientific, Bristol-Myers
treatment or not. We arenot able to discern definitively howmany Squibb, Cardionet, Centocor, Converge Medical Inc., Cordis, Dr.
patients were exposed toeach RFbeyond self-report, nor for how Reddy’s, Edwards Lifesciences, Esperion, GE Medical, Genentech,
long each CVRFwas present before entry inthe REACH Registry. Gilford, GSK, Guidant, J&J, Kensey-Nash, Lilly, Medtronic, Merck,
Individuals with unstable atherothrombotic disease at baseline Mytogen, Novartis, Novo Nordisk, Orphan Therapeutics, P&G
were excluded. Despite the large sample size, these findings may Pharma, Pfizer, Roche, Sankyo, sanofi-aventis, Schering-Plough,
not beextrapolated to patients with PAD who are identified from Scios, St. Jude Medical, Takeda, TMC, VasoGenix, Viacor.
other settings or who do nothavepreviouslyestablishedPAD. Fur- Prof. Creager is the recipient of research grants from sanofithermore,
patients enrolledinthe REACH Registryhad established aventis and Merck and is on the speaker’s bureau for the
PAD and the proportion of patients with symptomatic manifesta- Bristol-Myers Squibb –sanofi-aventis Partnership. He is aconsultions
of PADishigher compared with manyepidemiological studies tant for Genzyme, Merck, Sigma Tau, and Vascutec.
that detected PAD byABI measurement [24]. Generalizability to Prof. Liau has received honoraria from sanofi-aventis.
those patients with only abnormal ABI is therefore not possible. Prof. Goto has received honoraria and consulting fees from
As aresult, good RF control and treatment may beoverestimated Eisai, sanofi-aventis, Daiichi-Sankyo, GlaxoSmithKline, Bristolin
the REACH Registry, even if patients are not reaching targets Myers Scribb, Otsuka, Bayer, Schering-Plough, Takeda, Astellas,
for risk factor control and following guideline therapies. Finally, AstraZeneca, Novartis and Kowa. Prof. Goto also received research
as for all registries, the influence of recruitment biases cannot be grants from Pfizer, Ono, Eisai, Otsuka, Daiichi-Sankyo, sanofi-
known; however, substantial efforts were undertaken to ensurethe aventis, Takeda and Astellas within the last 3years.
inclusion of representative patients from everyparticipating coun- Prof. Röther has received payment for Speakers’ Bureau
try. Physicians were instructed to recruit consecutive patients, but and consultancy fees from Boehringer-Ingelheim, sanofi-aventis,
unlike inarandomized controlled trial, there were nolog books Bristol-Myers Squibb and Merck Sharpe and Dome.
audited to ensure compliance with such instructions.
Prof. Steg has receivedhonoraria for advisoryboardattendance
FOR ELECTRONIC
and consulting fees from AstraZeneca, Boehringer-Ingelheim,
Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharpe and Dohme,
5. ConclusionFOR FOR ELECTRONIC
and consulting fees from AstraZeneca, Boehringer-Ingelheim,
Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharpe and Dohme,
Conclusion
Nycomed, sanofi-aventis, Servier,Takeda, The Medicines Company;
speakers bureaufromBoehringer-Ingelheim, Bristol-Myers Squibb,
Patients with PADdonot achieve RF control as frequentlyasindi-
frequentlyasindi-
GlaxoSmithKline, Nycomed, sanofi-aventis, Servier, ZLB Behring
viduals with other establishedatherothrombotic diseases (i.e. CAD
and Research Grant from sanofi-aventis within the last 3years.
or CVD). Improved RF control is associated with apositive impact on
DISTRIBUTION
Dr. Hirsch has received research ONLY
ONLY
grants from Bristol-Myers
major CV events after1year of follow-up. The identifiedtreatment
Squibb and and sanofi-aventis and honoraria from sanofi-aventis.
disparities should should provide impetus for moredirected physician and
patient education, and serve tostimulate healthcare professionals
globally toadhere toguidelines that designate therapeutic targets
Acknowledgements
for patients with PAD.
We thank Dominique Roome, MD and In-Ha Kim, MD of
6. Conflict ofinterest disclosures for authors
sanofi-aventis, and Brian Gavin, PhD and Ashish Pradhan, MD of
Bristol-Myers Squibb, for their support of the REACH Registry. The
REACH Registry enforces anoghost-writing policy. Wethank the
REACH Editorial Support Group for providing editorial help and
assistance in preparing this manuscript including editing, checking
content and language, formatting, referencing and preparing
tables and figures. The REACH Registry isendorsed bythe World
Heart Federation.
Funding: The REACH Registry issponsored by sanofi-aventis
(Paris, France), Bristol-Myers Squibb (Princetown, NewJersey, USA),
and the Waksman Foundation (Tokyo, Japan). The sponsors provide
logistical support. All the publication activity is controlled by
the REACH RegistryGlobal Publication Committee (Ph. Gabriel Steg,
Deepak L. Bhatt, MarkAlberts, Ralph D’Agostino, Kim Eagle, Shinya
Goto, Alan T. Hirsch, Chiau-Suong Liau, Jean-Louis Mas, E. Magnus
Ohman, Joachim Röther, Sidney C.Smith, Peter W.F. Wilson).
All manuscripts in the REACH Registry are prepared by independent
authors who are not governed bythe funding sponsors and
are reviewed byanacademic publication committee before submission.
The funding sponsors have the opportunity to review
manuscript submissions but do not have authority to change any
aspect of amanuscript.
Appendix A
A.1. REACH Registry Global Publication Committee
Mark Alberts, MD, NorthWestern University Medical School,
Chicago; Deepak L. Bhatt, MD, VA Boston Healthcare System and

e92 P.P. Cacoub et al. /Atherosclerosis 204 (2009) e86–e92
Brigham and Women’s Hospital, Boston (chair); Ralph D’Agostino,
PhD, BostonUniversity,Boston; Kim Eagle, MD, University of Michigan,
Ann Arbor, Michigan; Shinya Goto, MD, PhD Tokai University
School of Medicine, Isehara, Kanagawa, Japan; Alan T. Hirsch, MD,
University of Minnesota School of Public Health and Minneapolis
Heart Institute Foundation and Minneapolis; Chiau-Suong Liau,
MD, PhD, Taiwan University Hospital and College of Medicine,
Taipei; Jean-Louis Mas, MD, Centre Raymond Garcin, Paris, France;
E. Magnus Ohman, MD, Duke University Medical Center, Durham,
NC;Joachim Röther,MD, Klinikum Minden, Minden, Germany; SidneyC.Smith,
MD, University of North Carolina at Chapel Hill, Chapel
Hill, North Carolina; P. Gabriel Steg, MD, Hôpital Bichat-Claude
Bernard, Paris, France (chair); Peter W.F.Wilson, MD, Emory University
School of Medicine, Atlanta, Georgia.
A.2. National coordinators
Australia: Christopher Reid, Victoria. Austria: Franz Aichner,
Linz; Thomas Wascher, Graz. Belgium: Patrice Laloux, Mont-
Godinne. Brazil: Denilson Campos de Albuquerque, Rio de Janeiro.
Bulgaria: Julia Djorgova, Sofia. Canada: Eric A. Cohen, Toronto,
Ontario. Chile: Ramon Corbalan, Santiago. China: Chuanzhen LV,
Frederiksberg. Finland: Ilkka Tierala, Helsinki. France: Jean-Louis
Mas, Patrice Cacoub and Gilles Montalescot, Paris. Germany: Klaus
Parhofer, Munich; Uwe Zeymer, Ludwigshafen; Joachim Röther,
Minden. Greece: Moses Elisaf, Ioannina. Interlatina (Guatemala):
Romulo Lopez, Guatemala City. Hong Kong: Juliana Chan, Shatin.
Hungary: György Pfliegler,Debrecen. Indonesia: Bambang Sutrisna,
Jakarta. Israel: Avi Porath, Beer Sheva. Japan: Yasuo Ikeda, Tokyo.
Lebanon: Ismail Ismail Khalil, Beirut. Beirut. Lithuania: Ruta Babarskiene, Kau- Kau-
nas. Malaysia: Robaayah Zambahari, Kuala Lumpur. Mexico: Efrain
Gaxiola, Jalisco. The Netherlands: Don Poldermans, Rotterdam.
Philippines: Maria Teresa B. Abola, Quezon City. Portugal: Victor
Gil, Amadora. Romania: Constantin Popa, Bucharest. Russia: Yuri
Belenkov and Elizaveta Panchenko, Moscow. Saudi Arabia: Hassan
Chamsi-Pasha, Jeddah. Singapore: YeoTiong Cheng, Singapore.
South Korea: Oh Dong-Joo, Seoul. Spain: Carmen Suarez, Madrid.
Switzerland: Iris Baumgartner, Bern. Taiwan: Chiau-Suong Liau,
Taipei. Thailand: Piyamitr Sritara, Bangkok. United Arab Emirates:
Wael Al Mahmeed, Abu Dhabi. United Kingdom: Jonathan Morrell,
Hastings. Ukraine: ViraTseluyko, Kharkov. United States: Mark
Alberts, Chicago, IL; Robert M. Califf, Durham, NC; Christopher P.
Cannon, Boston, MA; Kim Eagle, Ann Arbor, MI; Alan T. Hirsch,
Minneapolis, MN.
The list of REACH investigators is accessible online at
www.reachregistry.org.
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