Incidence of arterial cardiovascular events after venous thromboembolism: a systematic review and a meta-analysis

Background: Whether patients with unprovoked venous thromboembolism (VTE) have a higher risk of arterial cardiovascular events than the general population and patients with provoked VTE is a matter of debate. Objective: To perform a systematic review and a meta-analysis aimed at assessing the risk of arterial cardiovascular events in patients with unprovoked VTE as compared with both patients with provoked VTE and controls. Methods: A systematic search was performed. Studies reporting on (i) patients with confirmed VTE, (ii) a follow-up of at least 6 months and (iii) the incidence of arterial cardiovascular events (acute myocardial infarction and ischemic stroke) were included in the systematic review. Those studies reporting separate incidences of cardiovascular events in patients with unprovoked and provoked VTE or patients with unprovoked VTE and controls were included in the incidence rate meta-analysis. Results: Overall, 17 studies were included in the systematic review. The weighted mean incidence of arterial cardiovascular events was 0.46% [95% confidence interval (CI) 0.34-0.59] and 0.35% (95% CI 0.24-0.49) per patient-year in patients with unprovoked and provoked VTE, respectively. Six studies were included in the meta-analysis. The risk of arterial cardiovascular events appeared to be higher in patients with unprovoked VTE than in controls [incidence rate ratio (IRR) 1.87, 95% CI 1.32-2.65] and than in patients with provoked VTE (IRR 1.86, 95% CI 1.19-2.89). Conclusions: Patients with unprovoked VTE have a higher risk of arterial cardiovascular events than patients with provoked VTE over long-term follow-up.