Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis

Ann Intern Med. 2022 Feb;175(2):244-255. doi: 10.7326/M21-2625. Epub 2021 Dec 14.


Background: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown.

Purpose: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups.

Data sources: MEDLINE from 1 January 1995 until 1 January 2021.

Study selection: 16 studies assessing at least 1 diagnostic strategy.

Data extraction: Individual-patient data from 20 553 patients.

Data synthesis: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups.

Limitations: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds.

Conclusion: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds.

Primary funding source: Dutch Research Council. (PROSPERO: CRD42018089366).

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Fibrin Fibrinogen Degradation Products
  • Humans
  • Neoplasms* / complications
  • Neoplasms* / diagnosis
  • Probability
  • Pulmonary Embolism* / diagnosis
  • Pulmonary Embolism* / epidemiology
  • Venous Thromboembolism* / diagnosis
  • Venous Thromboembolism* / epidemiology


  • Fibrin Fibrinogen Degradation Products