Index clinical manifestation of venous thromboembolism predicts early recurrence type and frequency: A meta-analysis of randomized controlled trials

Background: Observational studies suggest index clinical manifestation of venous thromboembolism (VTE) predicts recurrence type. Data regarding the association between index manifestation and recurrence rates are conflicting. Objectives: To perform a meta-analysis of randomized controlled trials (RCTs) to determine the type and frequency of recurrent VTE (rVTE) in persons after an index deep vein thrombosis (DVT) or pulmonary embolism (PE). Patients/Methods: We searched bibliographic databases for RCTs of acute (early) treatment of rVTE in persons with an index DVT or PE (±DVT), enrolling ≥ 50 subjects anticoagulated ≥ 3-months and reporting types of rVTE. We pooled (random-effects) the proportion of rVTEs that were DVTs, PEs, and fatal PEs, the proportion of recurrent PEs that were fatal, and absolute rVTE rates. Results: In nine RCTs (N = 13 640; 413 rVTEs) evaluating persons with an index PE; 66% (95% CI, 60-72%) of rVTEs were PE and 27% (95% CI, 22-33%) were fatal PE. Among 25 RCTs (N = 17 340; 692 rVTEs) evaluating persons with an index DVT, 36% (95% CI, 29-44%) experienced a recurrent PE and 10% (95% CI, 7-13%) a fatal PE. Recurrent PEs following an index PE had a higher fatality rate than after an index DVT (41%; 95% CI, 33-48% vs. 25%; 95% CI, 18-33%; P = 0.007). The rVTE rate was higher following an index DVT compared with a PE (2.6%; 95% CI, 1.6-3.8% vs. 4.9%; 95% CI, 4.0-6.0%; P = 0.002). Conclusions: Our meta-analysis suggests most rVTEs will be the same type as the index event. While index DVTs are associated with a higher rVTE rate than index PEs; recurrent PEs are associated with high fatality.