Clinical research study
An International Model to Predict Recurrent Cardiovascular Disease

https://doi.org/10.1016/j.amjmed.2012.01.014Get rights and content

Abstract

Background

Prediction models for cardiovascular events and cardiovascular death in patients with established cardiovascular disease are not generally available.

Methods

Participants from the prospective REduction of Atherothrombosis for Continued Health (REACH) Registry provided a global outpatient population with known cardiovascular disease at entry. Cardiovascular prediction models were estimated from the 2-year follow-up data of 49,689 participants from around the world.

Results

A developmental prediction model was estimated from 33,419 randomly selected participants (2394 cardiovascular events with 1029 cardiovascular deaths) from the pool of 49,689. The number of vascular beds with clinical disease, diabetes, smoking, low body mass index, history of atrial fibrillation, cardiac failure, and history of cardiovascular event(s) <1 year before baseline examination increased risk of a subsequent cardiovascular event. Statin (hazard ratio 0.75; 95% confidence interval, 0.69-0.82) and acetylsalicylic acid therapy (hazard ratio 0.90; 95% confidence interval, 0.83-0.99) also were significantly associated with reduced risk of cardiovascular events. The prediction model was validated in the remaining 16,270 REACH subjects (1172 cardiovascular events, 494 cardiovascular deaths). Risk of cardiovascular death was similarly estimated with the same set of risk factors. Simple algorithms were developed for prediction of overall cardiovascular events and for cardiovascular death.

Conclusions

This study establishes and validates a risk model to predict secondary cardiovascular events and cardiovascular death in outpatients with established atherothrombotic disease. Traditional risk factors, burden of disease, lack of treatment, and geographic location all are related to an increased risk of subsequent cardiovascular morbidity and cardiovascular mortality.

Section snippets

Methods

The study design, selection of physicians,12 and baseline and follow-up experience of participants in the REACH Registry13, 14, 15 have been published previously. The current study included outpatients aged ≥45 years with established coronary artery disease, cerebrovascular disease, or peripheral arterial disease, with enrollment by their physician over a 7-month period on a worldwide basis between December 2003 and June 2004. Documented coronary artery disease consisted of one or more of the

Results

The baseline characteristics of the participants are shown in Table 1. Participants were followed for a maximum of 24 months, with mean follow-up of 19 and median of 21 months. There were 55,814 persons in the REACH Study who were eligible for these data analyses, and approximately 89% (n = 49,689) from the 5473 participating study sites in 44 countries had full information on covariates at baseline and complete follow-up. By random selection, two thirds of the participants were assigned to a

Discussion

This study uses multivariable Cox regression analysis to identify factors that contribute to the risk of secondary ischemic events in a large, contemporary registry of patients with established cardiovascular disease. The factors that were statistically significant in the analyses included traditional risk variables for initial cardiovascular disease events (age, smoking, diabetes mellitus, body mass index), variables related to cardiovascular disease burden (number of vascular beds involved,

Acknowledgment

We thank sanofi-aventis and Bristol-Myers Squibb for their support of the REACH Registry. We also acknowledge statistical support by Alain Richard, PhD, at sanofi-aventis. The REACH Registry enforces a no ghost-writing policy. The first draft was written by Dr. Wilson. We thank 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

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    Funding: The REACH Registry is sponsored by sanofi-aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The sponsors provide logistical support. All the publication activity is controlled by the REACH Registry Global Publication Committee (Ph. Gabriel Steg, Deepak L. Bhatt, Mark Alberts, Ralph D'Agostino, Kim Eagle, Shinya Goto, Alan T. Hirsch, Chiau-Suong Liau, Jean-Louis Mas, E. Magnus Ohman, Joachim Röther, Sidney C. Smith, and Peter W.F. Wilson). All manuscripts in the REACH Registry are prepared by independent authors who are not governed by the funding sponsors and are reviewed by an academic publication committee before submission. The funding sponsors have the opportunity to review manuscript submissions but do not have authority to change any aspect of a manuscript.

    Conflict of Interest: Dr Wilson has received research grants from sanofi-aventis within the last 3 years. Prof. D'Agostino has received consultancy fees from sanofi-aventis and grant support from Pfizer. Dr Bhatt discloses the following relationships: advisory board: Medscape Cardiology; board of directors: Boston VA Research Institute, Society of Chest Pain Centers; chair: American Heart Association Get With The Guidelines Science Subcommittee; honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); research grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, sanofi-aventis, The Medicines Company; unfunded research: FlowCo, PLx Pharma, Takeda. Dr Eagle has received consulting fees or served on paid advisory boards from the National Heart, Lung, and Blood Institute and the R.W. Johnson Foundation, and received grant support from sanofi-aventis. Dr Pencina has received consultancy fees from sanofi-aventis for work on this project. Dr Smith has received honoraria for consulting or Data and Safety Monitoring Board fees from sanofi-aventis, GlaxoSmithKline, Fournier, and AstraZeneca, and lecture fees for speaking at Continuing Medical Education symposia supported by unrestricted educational grants from Bayer, Pfizer, Merck, and sanofi-aventis. Dr Alberts discloses the following relationships: consultant/advisory board—AGA Medical, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Diadexus, Eli Lilly & Co, Genentech, KOS, Medicines Company, Merck, Novo Nordisk, PDL Biopharma Inc, Pfizer, Photo Thera, and sanofi-aventis; research grants—AGA Medical, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Novo Nordisk, Photo Thera, sanofi-aventis, and Schering Plough; speaker's bureau—AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Diadexus, Genentech, Medicines Company, Novo Nordisk, PDL Biopharma Inc, and sanofi-aventis; honoraria—AGA Medical, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Diadexus, Eli Lilly & Co, Genentech, KOS, Medicines Company, Merck, Novo Nordisk, PDL Biopharma Inc, Pfizer, sanofi-aventis, TAP Pharmaceuticals-Data and Safety Monitoring Board, and Schering Plough; review panel—TAP Pharmaceuticals-Data and Safety Monitoring Board, and Schering Plough. Dr Dallongeville has received consulting fees from Bristol-Myers Squibb, MSD, and sanofi-aventis; and lecture fees from MSD-SP and sanofi-aventis; and grant support from Pfizer. Prof. Goto has received honoraria and consulting fees from Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Kowa, Novartis, Otsuka, sanofi-aventis, Schering-Plough, and Takeda. Prof. Goto also received research grants from Eisai, Ono, sanofi-aventis, AstraZeneca, Kowa, and Pfizer within the past 3 years. Dr Hirsch has received research grants from Bristol-Myers Squibb, sanofi-aventis, AstraZeneca, and the National Heart, Lung, and Blood Institute; and consulting fees from Pfizer, Bristol-Myers Squibb, and sanofi-aventis. Prof. Ohman has received grant support from Bristol-Myers Squibb, The Medicines Company, Eli Lilly, sanofi-aventis, and Schering-Plough; consultancy fees from Abiomed, Datascope, Inovise, Liposcience, Response Biomedical, Savacor, and The Medicines Company; payment for speaker's bureau from CV Therapeutics and Schering-Plough within the past 3 years; and is a shareholder of Inovise, Medtronic, and Savacor. Prof. Röther has received payment for speakers' bureau and consultancy fees from sanofi-aventis, Boehringer Ingelheim, MSD, and Bristol-Myers Squibb. Dr Mas has received consulting fees from sanofi-aventis, Servier, and Bristol-Myers Squibb; and lecture fees from sanofi-aventis, Bristol-Myers Squibb, and Boehringer Ingelheim. Prof. Steg has received honoraria for advisory board attendance and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Medtronic, GlaxoSmithKline, Merck, Nycomed, sanofi-aventis, Servier, Astellas, and The Medicines Company; and payment for speakers' bureau from Boehringer Ingelheim, Bristol Myers-Squibb, GlaxoSmithKline, Medtronic, Nycomed, sanofi-aventis, and Servier. None of the other authors reported disclosures.

    Authorship: The authors had full access to the data and take full responsibility for its integrity. All authors have read and agree to the manuscript as written.

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