One-Year Cardiovascular Event Rates in Outpatients With Atherothrombosis

Steg, Ph. Gabriel MD
Bhatt, Deepak L. MD
Wilson, Peter W. F. MD
D'Agostino, Ralph Sr MD
Ohman, E. Magnus MD
Röther, Joachim MD
Liau, Chiau-Suong MD, PhD
Hirsch, Alan T. MD
Mas, Jean-Louis MD
Ikeda, Yasuo MD
Pencina, Michael J. PhD
Goto, Shinya MD

Département de Cardiologie, Hôpital Bichat-Claude Bernard, Paris, France (Dr Steg); Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio (Dr Bhatt); Cardiology Division, Emory University School of Medicine, Atlanta, Ga (Dr Wilson); Statistics and Consulting Unit, Department of Mathematics and Statistics, Boston University, Boston, Mass (Drs D'Agostino and Pencina); Division of Cardiology, Duke University, Durham, NC (Dr Ohman); Department of Neurology, Klinikum Minden, Minden, Germany (Dr Röther); Department of Internal Medicine, National Taiwan University Hospital and School of Medicine, Taipei, Taiwan (Dr Liau);Minneapolis Heart Institute Foundation and Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (Dr Hirsch); Service de Neurologie, Centre Raymond Garcin, Hôpital Sainte-Anne, Paris, France (Dr Mas); Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan (Dr Ikeda); and Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan (Dr Goto).

Corresponding Author: Ph. Gabriel Steg, MD, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France ([email protected]).

Author Contributions: Dr Steg had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Steg, Bhatt, Wilson, Ohman, Röther, Hirsch.

Acquisition of data: Steg, Liau, Ikeda, Goto.

Analysis and interpretation of data: Steg, Bhatt, Wilson, D'Agostino, Hirsch, Mas, Ikeda, Pencina, Goto.

Drafting of the manuscript: Steg, Bhatt, D'Agostino, Hirsch, Goto.

Critical revision of the manuscript for important intellectual content: Steg, Bhatt, Wilson, D'Agostino, Ohman, Röther, Liau, Hirsch, Mas, Ikeda, Pencina, Goto.

Statistical analysis: Bhatt, Wilson, D'Agostino, Pencina.

Obtained funding: Steg, Goto.

Administrative, technical, or material support: Steg, Röther, Goto.

Study supervision: Steg, Bhatt, Wilson, Ohman, Röther, Hirsch, Mas.

REACH Registry Executive Committee: Deepak L. Bhatt, MD, Cleveland Clinic, Cleveland, Ohio (cochair); Ph. Gabriel Steg, MD, Hôpital Bichat-Claude Bernard, Paris, France (cochair); E. Magnus Ohman, MD, Duke University Medical Center, Durham, NC; Joachim Röther, MD, Klinikum Minden, Minden, Germany; Peter W. F. Wilson, MD, Medical University of South Carolina, Charleston.

REACH Registry Publication Committee: Deepak L. Bhatt, MD, Cleveland Clinic, Cleveland, Ohio (cochair); Ph. Gabriel Steg, MD, Hôpital Bichat-Claude Bernard, Paris, France (cochair); Shinya Goto, MD, Tokai University School of Medicine, Isehara, Kanagawa, Japan; Alan T. Hirsch, MD, Minneapolis Heart Institute Foundation and Division of Epidemiology and Community Health, University of Minnesota School of Public Health, 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; Peter W. F. Wilson, MD, Medical University of South Carolina, Charleston.

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 Khalil, Beirut. Lithuania: Ruta Babarskiene, Kaunas. Malaysia: Robaayah Zambahari, Kuala Lumpur. Mexico: Efrain Gaxiola, Jalisco. the Netherlands: Don Poldermans, Rotterdam. Philippines: M. 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: Yeo Tiong 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 Mahameed, Abu Dhabi. United Kingdom: Jonathan Morrell, Hastings. Ukraine: Vira Tseluyko, Kharkov. United States: Mark Alberts, Chicago, Ill; Robert M. Califf, Durham, NC; Christopher P. Cannon, Boston, Mass; Kim Eagle, Ann Arbor, Mich; Alan T. Hirsch, Minneapolis, Minn.

The List of REACH investigators is accessible online at http://www.reachregistry.org.

Financial Disclosures: Dr Bhatt reports that he has received honoraria for consulting on scientific advisory boards from AstraZeneca, Bristol-Myers Squibb, Centocor, Eisai, Eli Lilly, GlaxoSmithKline, Millennium, Otsuka, Paringenix, PDL, Sanofi-Aventis, Schering Plough, The Medicines Company; honoraria for lectures from Bristol-Myers Squibb, Sanofi-Aventis, and The Medicines Company; and provided expert testimony regarding clopidogrel (the compensation was donated to a nonprofit organization). Dr Röther reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis. Dr Steg reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis and has received research grants from Sanofi-Aventis. Dr Steg reports having served as a member of the speakers' bureau for Boehringer Ingelheim, Servier, GlaxoSmithKline, Merck, Sharp & Dohme, and Nycomed and also on a consultant ad board for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp & Dohme, Sanofi-Aventis, Servier, and Takeda. Dr Ohman reports that he has received research grants from Berlex, Sanofi-Aventis, Schering-Plough, Eli Lilly, Bristol-Myers Squibb, and Millennium. Dr Ohman reports that he has stock ownership in Medtronic, Savacor, and Response Biomedical and is a consultant for Invoise, Response Biomedical, Savacor, and Liposcience. Dr Hirsch reports that he has received research grants from Bristol-Myers Squibb and Sanofi-Aventis; honoraria from Sanofi-Aventis; and speaker's bureau fees for Sanofi-Aventis. Dr Wilson reports that he has received a grant from Sanofi-Aventis. None of the other authors reported disclosures.

Funding/Support: The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan), who assisted with the design and conduct of the study and data collection.

Role of the Sponsor: Data analysis and interpretation, as well as preparation, review, and approval of the manuscript, were done independently by academic authors who are not governed by the funding sponsors and under the control of an academic publications committee. The funding sponsors have the opportunity to review manuscript submissions but do not have authority to change any aspect of a manuscript.

Statistical Analysis: The statistical analysis for this study was performed under the supervision of Drs D'Agostino and Pencina from the Statistics and Consulting Unit, Department of Mathematics and Statistics, Boston University, Boston, Mass.

Acknowledgment: We thank Veronique Daclin, MD, and Luc Sagnard, MD, of Sanofi-Aventis, and Brian Gavin, PhD, of Bristol-Myers Squibb, for their support of the REACH Registry, as part of their regular duties.

A Complete List of the REACH Registry Investigators appears in JAMA (2006;295:180–189).

JAMA: The Journal of the American Medical Association 297(11):p 1197-1206, March 21, 2007.

Context

Few data document current cardiovascular (CV) event rates in stable patients with atherothrombosis in a community setting. Differential event rates for patients with documented coronary artery disease (CAD), cerebrovascular disease (CVD), or peripheral arterial disease (PAD) or those at risk of these diseases have not been previously evaluated in a single international cohort.

Objective

To establish contemporary, international, 1-year CV event rates in outpatients with established arterial disease or with multiple risk factors for atherothrombosis.

Design, Setting, and Participants

The Reduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective cohort of 68 236 patients with either established atherosclerotic arterial disease (CAD, PAD, CVD; n = 55 814) or at least 3 risk factors for atherothrombosis (n = 12 422), who were enrolled from 5587 physician practices in 44 countries in 2003–2004.

Main Outcome Measures

Rates of CV death, myocardial infarction (MI), and stroke.

Results

As of July 2006, 1-year outcomes were available for 95.22% (n = 64 977) of participants. Cardiovascular death, MI, or stroke rates were 4.24% overall: 4.69% for those with established atherosclerotic arterial disease vs 2.15% for patients with multiple risk factors only. Among patients with established disease, CV death, MI, or stroke rates were 4.52% for patients with CAD, 6.47% for patients with CVD, and 5.35% for patients with PAD. The incidences of the end point of CV death, MI, or stroke or of hospitalization for atherothrombotic event(s) were 15.20% for CAD, 14.53% for CVD, and 21.14% for PAD patients with established disease. These event rates increased with the number of symptomatic arterial disease locations, ranging from 5.31% for patients with risk factors only to 12.58% for patients with 1, 21.14% for patients with 2, and 26.27% for patients with 3 symptomatic arterial disease locations (P<.001 for trend).

Conclusions

In this large, contemporary, international study, outpatients with established atherosclerotic arterial disease, or at risk of atherothrombosis, experienced relatively high annual CV event rates. Multiple disease locations increased the 1-year risk of CV events.