Wells Rule and d-Dimer Testing to Rule Out Pulmonary Embolism: A Systematic Review and Individual-Patient Data Meta-analysis

Abstract

Background: The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear.

Purpose: To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted d-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older.

Data sources: MEDLINE and EMBASE from 1 January 1988 to 13 February 2016.

Study selection: 6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative d-dimer testing.

Data extraction: Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool.

Data synthesis: The proportion of patients in whom imaging could be withheld based on a "PE-unlikely" Wells score and a negative d-dimer test result (efficiency) was estimated using fixed (≤500 µg/L) and age-adjusted (age × 10 µg/L in patients aged >50 years) d-dimer thresholds; their 3-month incidence of symptomatic venous thromboembolism (failure rate) was also estimated. Overall, efficiency increased from 28% to 33% when the age-adjusted (instead of the fixed) d-dimer threshold was applied. This increase was more prominent in elderly patients (12%) but less so in inpatients (2.6%). The failure rate of age-adjusted d-dimer testing was less than 3% in all examined subgroups.

Limitation: Post hoc analysis, between-study differences in patient characteristics, use of various d-dimer assays, and limited statistical power to assess failure rate.

Conclusion: Age-adjusted d-dimer testing is associated with a 5% absolute increase in the proportion of patients with suspected PE in whom imaging can be safely withheld compared with fixed d-dimer testing. This strategy seems safe across different high-risk subgroups, but its efficiency varies.

Primary funding source: None.