Evaluation of Venous Thromboembolism Recurrence Scores in an Unprovoked Pulmonary Embolism Population: A Post-hoc Analysis of the PADIS-PE trial

Am J Med. 2020 Aug;133(8):e406-e421. doi: 10.1016/j.amjmed.2020.03.040. Epub 2020 Apr 22.


Background: We aimed to validate the Men Continue and HERDOO2 (HERDOO2), D-dimer, age, sex, hormonal therapy (DASH), and updated Vienna recurrent venous thromboembolism prediction models in a population composed entirely of first unprovoked pulmonary embolism, and to analyze the impact of the addition of the pulmonary vascular obstruction index (PVOI) on score accuracy.

Methods: Analyses were based on the double-blind, randomized PADIS-PE trial, which included 371 unprovoked pulmonary embolism patients initially treated for 6 months, successively randomized to receive an additional 18 months of warfarin or placebo, and subsequently followed-up for 2 years.

Results: The HERDOO2, DASH, and updated Vienna scores displayed C-statistics of 0.61 (95% CI 0.54-0.68), 0.60 (95% CI 0.53-0.66), and 0.58 (95% CI 0.51-0.66), respectively. Only the HERDOO2 score identified low recurrence risk patients (<3%/year) after anticoagulation was stopped. When added to either of the prediction models, PVOI measured at pulmonary embolism diagnosis, after 6 months of anticoagulation, or both, improved scores' C-statistics between +0.06 and +0.11 points and consistently led to identifying at least 50% of patients who experienced recurrence but in whom the scores would have indicated against extended anticoagulation.

Conclusions: In patients with a first unprovoked pulmonary embolism, the HERDOO2 score is able to identify patients with a low recurrence risk after treatment discontinuation. Addition of PVOI improves accuracy of all scores.

Clinical trials registration: URL: http://www.controlled-trials.com. Unique identifier: NCT00740883.

Keywords: Randomized trial; Recurrent venous thromboembolism; Risk factors; Unprovoked pulmonary embolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Anticoagulants / therapeutic use*
  • Duration of Therapy
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Pulmonary Embolism / diagnostic imaging
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / epidemiology*
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Risk Assessment
  • Sex Factors
  • Venous Thromboembolism / epidemiology*
  • Venous Thrombosis / epidemiology*
  • Ventilation-Perfusion Scan
  • Warfarin / therapeutic use


  • Anticoagulants
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Warfarin

Associated data

  • ClinicalTrials.gov/NCT00740883