Venous thromboembolism and cardiovascular risk: results from the NAVIGATOR trial

Am J Med. 2015 Mar;128(3):297-302. doi: 10.1016/j.amjmed.2014.08.022. Epub 2014 Nov 20.

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 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 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 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, myocardial infarction, and stroke, as compared with patients without venous thromboembolism (10.7% vs 5.9%; P < .001; adjusted hazard ratio 2.12; 95% confidence interval, 1.36-3.31; P = .001).

Conclusion: In patients with impaired glucose tolerance at high risk for cardiovascular events, the prevalence of venous thromboembolism was rare but associated with worse long-term cardiovascular outcomes, including arterial events. Venous thromboembolism is a marker of risk, and attention should be paid to this high-risk group of patients.

Trial registration: ClinicalTrials.gov NCT00097786.

Keywords: Cardiovascular; Outcomes; Venous thrombosis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage*
  • Cardiovascular Diseases / epidemiology*
  • Confidence Intervals
  • Cyclohexanes / administration & dosage*
  • Female
  • Glucose Intolerance / blood
  • Glucose Intolerance / drug therapy*
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Middle Aged
  • Nateglinide
  • Outcome Assessment, Health Care
  • Phenylalanine / administration & dosage
  • Phenylalanine / analogs & derivatives*
  • Prevalence
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Tetrazoles / administration & dosage*
  • Time Factors
  • Valine / administration & dosage
  • Valine / analogs & derivatives*
  • Valsartan
  • Venous Thromboembolism / epidemiology*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Cyclohexanes
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Tetrazoles
  • Nateglinide
  • Phenylalanine
  • Valsartan
  • Valine

Associated data

  • ClinicalTrials.gov/NCT00097786