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A clinical assessment protocol proved to be as effective as blood testing and CT imaging in the emergency department setting for ruling out pulmonary embolism in very low-risk patients in a newly reported French clinical trial.
The crossover cluster-randomized PROPER study was conducted at 14 emergency departments (EDs) in France to assess the diagnostic efficacy of the pulmonary embolism rule-out criteria (PERC) among low-risk patients with suspected pulmonary embolism (PE).
Action Points
- Note that this randomized trial demonstrated that a set of rule-out criteria for PE may be as effective as more formal d-dimer and CT angio testing in the emergency department.
- While some PEs were likely missed in the PERC group, similar overall outcomes suggest that perhaps low-risk PEs may not warrant aggressive treatment.
Use of PERC was associated with a lower initial PE diagnosis, along with an 8% decrease in unnecessary CT scanning and a median 40-minute decrease in ED stay, compared with usual care.
PERC is a measure of eight objective factors linked to PE: arterial oxygen saturation (SpO2) of 94% or less, unilateral leg swelling, hemoptysis, recent trauma or recent surgery, prior PE or prior deep venous thrombosis, pulse rate of at least 100 beats/minute, patient age of 50 years or older, and exogenous estrogen use.
D-dimer assay and computed tomographic pulmonary angiography (CTPA) are commonly used in the ED setting to test for PE, but their is concern that over-use of these screening tools, especially CTPA, has led to overdiagnosis of PE, wrote PROPER Investigative Group lead author Yonathan Freund, MD, PhD, and colleagues, in the Feb 13
Introduced in 2004, the PERC rule was designed to reduce overtesting for PE in the ED setting by utilizing the clinical assessment and intuition of the attending physician.
In EDs in the United States, a negative PERC (all eight measures negative) has been shown to be highly predictive for ruling out PE. But several retrospective studies conducted in Europe showed a much higher false-negative rate, raising concerns that PERC may not be a useful tool in Europe and other regions with higher prevalence of PE than the United States.
"This multicenter noninferiority randomized clinical trial was conducted to test the hypothesis that the diagnosis of PE can be safely excluded among ED patients with a low clinical probability and a PERC score of zero without further diagnostic testing," Freund and colleagues wrote.
The study included 1,916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), with 962 assigned to the PERC group and 954 assigned to the control group. In all, 1,749 patients completed the trial.
In the control group, the diagnostic work-up included initial physician assessment of low PE probability, followed by D-dimer testing and CTPA when D-dimer was positive. In the PERC group, a PERC score of 0 resulted in no further testing, and a higher PERC score resulted in usual testing.
The principal study endpoint was symptomatic PE at three months.
The participating EDs were randomized to use the PERC rule (intervention group, 7 EDs) or not use the PERC rule (control group, 7 other EDs). After a 2-month washout period the sites were crossed over.
Among the main findings:
- PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) versus 14 (1.5%) in the PERC group (difference, 1.3%, 95% CI, −0.1% to 2.7%; P=0.052).
- One PE (0.1%) was diagnosed during follow-up in the PERC group versus none in the control group (difference, 0.1%, 95% CI, −∞ to 0.8%).
- CTPA was performed in 13% of PERC patients compared with 23% of patients in the control group (difference, −10%, 95% CI, −13% to −6%; P<0.001).
- In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes, 95% CI, 4 to 68) and hospital admission (difference, 3.3%, 95% CI, 0.1% to 6.6%).
Comparison of the frequency of PE diagnosis with usual care and frequency diagnosed with the PERC rule showed that PERC resulted in a 1.3% absolute, or 48% relative, lower initial PE diagnosis rate, with 3-month outcomes similar in both groups.
In an editorial published with the study, Jeffrey A. Kline, MD, of the Indiana University School of Medicine at Indianapolis, wrote that the findings raise questions about the use of anticoagulation treatment in some patients.
"Although PROPER was not designed to examine the issue of withholding treatment for mild PE, this difference in diagnosis rate raises another important clinical management controversy - should some minor PEs be left untreated?" Kline asked.
"Relevant to this question, five patients in the PROPER trial were diagnosed with subsegmental PE with usual care, compared with one patients diagnosed with subsegmental PE using PERC. It has been suggested that some isolated subsegmental PEs do not warrant anticoagulation, but this issue remains unresolved."
Disclosures
This research was funded by Programme Hospitalier de Recherche Clinique-PHRC 2014.
The researchers reported no relevant relationships with industry related to this study.
Primary Source
JAMA
Freund Y, et al. "Effect of the pulmonary embolism rule-out criteria on subsequent thromboembolic events among low-risk emergency department patients: the PROPER randomized clinical trial" JAMA 2018; DOI: 10.1001/jama.2017.21904.