Derivation and Validation of a 4-Level Clinical Pretest Probability Score for Suspected Pulmonary Embolism to Safely Decrease Imaging Testing

Abstract

Importance: In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern.

Objective: To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE.

Design, setting, and participants: This study included consecutive outpatients suspected of having PE from US and European emergency departments. Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort. The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%). A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer. Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019.

Main outcomes and measures: The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing.

Results: Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years. The 4PEPS comprises 13 clinical variables scored from -2 to 5. It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 μg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test. In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively. The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively. The absolute reductions in imaging testing were -22% (95% CI, -26 to -19) and -19% (95% CI, -22 to -16) in the first and second external validation cohorts, respectively. The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing.

Conclusions and relevance: The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE. It should now be tested in a formal outcome study.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Roy has received grants from the French Health Ministry as well as personal fees and nonfinancial support from Bayer Health Care, Boehringer Ingelheim France, Bristol Myers Squibb, Pfizer, Aspen, Daiichi Sankyo, and Sanofi Aventis France outside the submitted work. Dr Kline has received grants from the National Institutes of Health, Stago Diagnostica, Janssen/Johnson & Johnson, and Pfizer/Bristol Myers Squibb outside the submitted work. Dr Righini has received grants from the Swiss National Research Foundation. Dr Le Gal has received grants from the French Health Ministry, Portola Pharmaceuticals, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, LEO Pharma, Daiichi Sankyo, and Bayer as well as personal fees from Bayer, Pfizer, LEO Pharma, Sanofi, and bioMérieux. Dr Moumneh has received grants from the French Health Ministry, Société Française de Médecine d’Urgence, and CanVECTOR Network outside the submitted work. Dr Penaloza has received grants from Fondation Saint Luc and Bristol Myers Squibb; grants and personal fees from Bayer; and personal fees and nonfinancial support from Boehringer Ingelheim, Daiichi Sankyo, Sanofi, Stago Diagnostica, Bristol Myers Squibb, Aspen, and Roche outside the submitted work. No other disclosures were reported.

Figures

Figure.. Pulmonary Embolism Prevalence by 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS) in the Derivation and Validation Cohorts