Accepted Manuscript Venous Thromboembolism and Cardiovascular Risk: Results from the NAVIGATOR Trial Marcelo Katz , MD, Robert M. Califf , MD, Jie-Lena Sun , MS, John J.V. McMurray , MD, Laine Thomas , PhD, Renato D. Lopes , MD, PhD, MHS PII:
S0002-9343(14)00788-8
DOI:
10.1016/j.amjmed.2014.08.022
Reference:
AJM 12668
To appear in:
The American Journal of Medicine
Received Date: 11 March 2014 Revised Date:
11 July 2014
Accepted Date: 10 August 2014
Please cite this article as: Katz M, Califf RM, Sun JL, McMurray JJV, Thomas L, Lopes RD, Venous Thromboembolism and Cardiovascular Risk: Results from the NAVIGATOR Trial, The American Journal of Medicine (2014), doi: 10.1016/j.amjmed.2014.08.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Venous Thromboembolism and Cardiovascular Risk: Results from the NAVIGATOR Trial
Marcelo Katz, MD,a,b Robert M. Califf, MD,c Jie-Lena Sun, MS,d John J.V. McMurray, MD,e
RI PT
Laine Thomas, PhD,d Renato D. Lopes, MD, PhD, MHSd
a
Brazilian Clinical Research Institute, Sao Paulo, Brazil; bHospital Israelita Albert Einstein, Sao Paulo,
SC
Brazil; cDuke Translational Medicine Institute, dDuke Clinical Research Institute, Duke University Medical Center, Durham, NC; eBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland,
M AN U
UK.
Word count: 1797 (including abstract, text, and acknowledgements)
Funding: The NAVIGATOR trial was funded by Novartis Pharmaceuticals. Conflict of Interest: Califf: https://dcri.org/about-us/conflict-of-interest/Califf-COI_Jan-
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March_2014.docx; Lopes: https://dcri.org/about-us/conflict-of-
interest/COI_Renato_Lopes_2014.pdf; the remaining authors have nothing to report. Author statement: All authors participated in the design, preparation, and review of the manuscript. Dr.
EP
Lopes takes responsibility for the integrity of the work, from inception to published article. Article type: Clinical research study
AC C
Key words: Venous thrombosis; cardiovascular; outcomes Running title: Venous Thromboembolism and Cardiovascular Risk
Address for correspondence: Renato D. Lopes, MD, PhD, MHS, Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Room 0311 Terrace Level, Durham, NC 27705. Phone: (919) 668-8241; Fax: (919) 668-7056. E-mail: [email protected]
ACCEPTED MANUSCRIPT 2
ABSTRACT Background: Contemporary studies suggest an association between venous thromboembolism and a higher incidence of major cardiovascular events, mostly attributed to arterial atherothrombosis. Using data from the
RI PT
Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, we assessed the association of venous thromboembolism with major cardiovascular events.
Methods: In NAVIGATOR, patients with impaired glucose tolerance were randomly allocated to receive
SC
valsartan or placebo and nateglinide or placebo in addition to lifestyle modification. Baseline characteristics and prior history of venous thromboembolism were assessed. After adjusting for important baseline
M AN U
covariates, Cox proportional hazards regression models were used to assess the association between venous thromboembolism and major cardiovascular outcomes.
Results: Of the 9306 patients enrolled, 129 (1.4%) had a history of venous thromboembolism. Patients with venous thromboembolism were older, more frequently white and female, and had a higher body mass index. Patients with venous thromboembolism had higher 5-year event rates for the composite of death,
TE D
myocardial infarction, and stroke as compared with patients without venous thromboembolism (10.7% vs. 5.9%; P
S0002-9343(14)00788-8
DOI:
10.1016/j.amjmed.2014.08.022
Reference:
AJM 12668
To appear in:
The American Journal of Medicine
Received Date: 11 March 2014 Revised Date:
11 July 2014
Accepted Date: 10 August 2014
Please cite this article as: Katz M, Califf RM, Sun JL, McMurray JJV, Thomas L, Lopes RD, Venous Thromboembolism and Cardiovascular Risk: Results from the NAVIGATOR Trial, The American Journal of Medicine (2014), doi: 10.1016/j.amjmed.2014.08.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Venous Thromboembolism and Cardiovascular Risk: Results from the NAVIGATOR Trial
Marcelo Katz, MD,a,b Robert M. Califf, MD,c Jie-Lena Sun, MS,d John J.V. McMurray, MD,e
RI PT
Laine Thomas, PhD,d Renato D. Lopes, MD, PhD, MHSd
a
Brazilian Clinical Research Institute, Sao Paulo, Brazil; bHospital Israelita Albert Einstein, Sao Paulo,
SC
Brazil; cDuke Translational Medicine Institute, dDuke Clinical Research Institute, Duke University Medical Center, Durham, NC; eBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland,
M AN U
UK.
Word count: 1797 (including abstract, text, and acknowledgements)
Funding: The NAVIGATOR trial was funded by Novartis Pharmaceuticals. Conflict of Interest: Califf: https://dcri.org/about-us/conflict-of-interest/Califf-COI_Jan-
TE D
March_2014.docx; Lopes: https://dcri.org/about-us/conflict-of-
interest/COI_Renato_Lopes_2014.pdf; the remaining authors have nothing to report. Author statement: All authors participated in the design, preparation, and review of the manuscript. Dr.
EP
Lopes takes responsibility for the integrity of the work, from inception to published article. Article type: Clinical research study
AC C
Key words: Venous thrombosis; cardiovascular; outcomes Running title: Venous Thromboembolism and Cardiovascular Risk
Address for correspondence: Renato D. Lopes, MD, PhD, MHS, Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Room 0311 Terrace Level, Durham, NC 27705. Phone: (919) 668-8241; Fax: (919) 668-7056. E-mail: [email protected]
ACCEPTED MANUSCRIPT 2
ABSTRACT Background: Contemporary studies suggest an association between venous thromboembolism and a higher incidence of major cardiovascular events, mostly attributed to arterial atherothrombosis. Using data from the
RI PT
Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, we assessed the association of venous thromboembolism with major cardiovascular events.
Methods: In NAVIGATOR, patients with impaired glucose tolerance were randomly allocated to receive
SC
valsartan or placebo and nateglinide or placebo in addition to lifestyle modification. Baseline characteristics and prior history of venous thromboembolism were assessed. After adjusting for important baseline
M AN U
covariates, Cox proportional hazards regression models were used to assess the association between venous thromboembolism and major cardiovascular outcomes.
Results: Of the 9306 patients enrolled, 129 (1.4%) had a history of venous thromboembolism. Patients with venous thromboembolism were older, more frequently white and female, and had a higher body mass index. Patients with venous thromboembolism had higher 5-year event rates for the composite of death,
TE D
myocardial infarction, and stroke as compared with patients without venous thromboembolism (10.7% vs. 5.9%; P
