Effect of a diagnostic strategy using an elevated and age-adjusted D-dimer threshold on thromboembolic events in emergency department patients with suspected pulmonary embolism: a randomized clinical trial
Freund Y, Chauvin A, Jimenez S, et al. JAMA. 2021;326(21):2141-2149.
Two commonly used risk-stratification tools for pulmonary embolism (PE) are the PE rule-out criteria (PERC) and age-adjusted D-dimer (which raises the positive cut point to age × 10 ng/mL for patients above 50 years of age).
A newer tool is YEARS, which raises the D-dimer cut point to 1,000 ng/mL if a patient has no YEARS criteria (PE as the most likely diagnosis, clinical signs of deep venous thrombosis, and hemoptysis).
Although YEARS has had excellent derivation and initial validation work published in the Lancet and compelling external validation from sites across the U.S., the authors of this study performed the first randomized trial assessing the safety of combining YEARS with PERC and age-adjusted D-dimer (AADD).
This was a cluster randomized, crossover, noninferiority trial from 18 EDs in France and Spain enrolling patients with low pretest probability of PE who were not PERC negative and patients with intermediate pretest probability.
Each participating ED was randomized to either the control strategy for 4 months followed by a washout period and the intervention for 4 months, or the reverse.
In the control strategy, PE was ruled out if AADD was negative, or if imaging was negative with an elevated D-dimer.
In the intervention, PE was ruled out if YEARS was negative (with YEARS applied first), if AADD was negative, or if imaging was negative with an elevated D-dimer if a patient had ≥1 YEARS criteria.
The primary endpoint was venous thromboembolism at 3 months; the noninferiority margin was 1.35%.
The study enrolled 1,414 patients (mean age of 55 years; 58% women) and presents data largely on 1,217 (86%) patients for the per-protocol analysis (some patients were excluded because of protocol violations or were lost to follow-up (n = 37).
A total of 6 PEs were diagnosed at 3 months: 1 in the intervention group and 5 in the control group. The failure rates were 0.15% and 0.80% in the intervention and control groups, respectively; the confidence estimate of the difference was within the prespecified noninferiority margin.
Among several secondary outcomes, including mortality and admission, chest imaging notably differed between groups (30.4% in the intervention group vs 40.0% in the control group).
In a posthoc analysis examining safety, no missed PEs were found in the 515 patients in the intervention group who were YEARS negative, with a failure rate of 0%.
Although this was a well-done international study, some limitations include a nonconsecutive enrollment strategy, protocol deviations occurring in 40 patients (29 patients received imaging despite a negative D-dimer, and 11 did not receive imaging despite a positive D-dimer), and 37 patients were lost to follow-up. In sensitivity analyses with a multiple-imputation strategy, the results were unchanged.
EDITOR’S COMMENTARY: This is a large, well-conducted randomized trial adding to the evidence that YEARS can be used to safely decrease imaging in patients being worked up for PE (absolute 10% difference in this article). This is also the first study to suggest that a combination strategy of YEARS with AADD and PERC, although complicated to remember, does appear to be noninferior to a more conventional approach.
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Sean R. - April 3, 2022 2:18 PM
my apologies i meant to age times 10 not 100 thus the adding a zero shortcut
Samuel C. - May 17, 2022 5:55 PM
Did you reviewed the article on the 4PEPS score? JAMA march 2021