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Freund Y. "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. 319(6):559-566.
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Clinical Question

In adult patients that present to the Emerg department with low clinical probability of pulmonary embolism (PE), does the use of the Pulmonary Embolism Rule-out Criteria (PERC) safely exclude the diagnosis of PE?

Bottom Line

In the Emerg with patients with very low clinical suspicion of PE, use of PERC-based strategy was non-inferior to usual care at 3-months.

Major Points

Diagnostic strategy for pulmonary embolism (PE) in Emerg is well established and described[1] utilizing evaluation of clinician's assessment of probability, followed by D-dimer and computed tomographic pulmonary angiography (CTPA). The 8-item pulmonary embolism rule-out criteria (PERC)[2] rule, derived from a population of patients with a low risk of PE (<1.8%) and meta-analysis suggested a <1% prevalence of PE in PERC-negative patients.[3] The PERC rule should be used in patients where the risk of further evaluation for PE would be unfavourable.

In this cluster-randomized non-inferiority trial conducted in 14 French emergency departments of 1916 very low-risk patients with suspected PE, randomization to a PERC-strategy vs. usual care did not result in an inferior rate of thromboembolic events or all-cause mortality over 3 months. There was only 1 diagnostic failure in the PERC group where the patient failed diagnosis with D-dimer and CTPA and was found with V/Q scan. In addition, the PERC strategy was associated with a benefit in terms of reduced CTPA use(-9.7%), ED length of stay (-36 min), and likelihood of initial admission into hospital (-3.3%).

The PE prevalence was lower than previous trials and thus the sample size calculation was inaccurate. Bias may have been introduced in the control periods that was not recorded and with 3% of the population lost to follow-up, the non-inferiority margin could have been lost. This trial demonstrated a cost-free strategy for decreasing use of CTPA and emerg length of stay.


As of February 2018, no guidelines have been published that reflect the results of this trial.


  • Multicenter, non-inferiority, crossover cluster–randomized clinical trial
  • N=1916
    • PERC Periods (n=962)
    • Usual Care Periods (n=954)
  • Setting: 14 Emerg Departments in France
  • Enrollment: August 2015 - December 2016
  • Mean follow-up: 3 months
  • Analysis: Intention-to-treat, 1.5% non-inferiority margin
  • Primary Outcome: Failure of diagnostic criteria


Inclusion Criteria

  • new-onset presence or worsening of shortness of breath or chest pain
  • low clinical probability of PE estimated by the treating physician’s gestalt as an expectation below 15%[4]

Exclusion Criteria

  • obvious etiology to the acute presentation other than PE
  • acute severe presentation (hypotension, SpO2<90%, respiratory distress)
  • contraindication to CTPA (impaired renal function with an estimated creatinine clearance <30 mL/min; known allergy to intravenous radioopaque contrast)
  • pregnancy
  • inability to be followed up
  • receiving any anticoagulant therapy for other indication

Baseline Characteristics

PERC Group shown

  • Demographics: Mean age 44 years, female 51%
  • Comorbidities: Respiratory 3%, Heart failure 2%, Stroke 1%
  • Emerg presentation: Chest pain 91%, Shortness of Breath 32%, Syncope 1%
  • Physiologic parameters: mean heart rate 82, HR >100 beats/min 13%, mean respiratory rate 18, median SpO2 99, mean systolic blood pressure 136, mean temperature 36.7 degC
  • Anthropomorphics: Weight
  • PE Risks: exogenous estrogens 7%, DVT 4%, history of VTE 3%, surgery or trauma within 1 month 2%, hemoptysis 1%, active malignancy 1%
    • Simplified Revised Geneva Score: low risk 86%, intermediate risk 14%
    • Wells score: low 91%, Intermediate risk 8%, high 1%
    • PERC score: Zero 48%, positive 52%


  • 6 months PERC-based strategy[2] if PERC score positive, usual diagnostic criteria applied
    • PERC Criteria:
      • SpO2 < 94%
      • HR ≥ 100/min
      • patient age ≥ 50 years
      • unilateral leg swelling
      • hemoptysis
      • recent trauma or surgery
      • prior PE or DVT
      • exogenous estrogen use
  • 6 months usual care[1]
    • if low clinician gestalt of PE then D-dimer
    • if D-dimer positive then CTPA


Comparisons are PERC-strategy vs. Usual care.

Primary Outcomes

Thrombotic event at 3 months
3% vs. 3% (P = 0.12)

Secondary Outcomes

13% vs. 23% (difference 9.7%, P < 0.001, NNT 10)
Length of ED stay, median h-min
4:36 vs. 5:14 (difference -00:36, P < 0.001)
Hospital admission
13% vs. 16% (difference 3.3%, P = 0.04, NNT 30)
Anti-coagulation therapy initiated
2% vs. 3% (difference 1.3%, P = 0.09)
Hospital readmission at 3 months
4% vs. 7% (difference 2.1%, P = 0.051, NNT 48)
All-cause mortality at 3 months
0.3% vs. 0.2% (difference 0.1%, P > 0.99)

Subgroup Analysis

48% vs. 38%
Tested with D-dimer
55% vs. 99%
D-dimer < 0.5 mcg/mL
35% vs. 50%
PE diagnosed in Emerg
1.5% vs. 2.7%

Adverse Events

None observed


  • PE prevalence was lower than previous trials
  • CTPA was considered positive if it showed an isolated subsegmental PE and could over-estimate prevalence as these PEs could be left untreated
  • Sample size estimation was inaccurate, diagnostic failure in control group was less than estimated
  • Non-patient level randomization was utilized
  • With 54 patients (2.8%) lost to follow-up, a few events occurring in this group could have changed outcomes. Worst-case scenario analysis led to rejection of non-inferiority


  • Sponsor was Assistance Publique-Hôpitaux de Paris
  • Grant from Programme Hospitalier de Recherche Clinique-PHRC 2014 (Ministère de la Santé, Paris, France)

Further Reading

  1. 1.0 1.1 Konstantinides SV et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur. Heart J. 2014. 35:3033-69, 3069a-3069k.
  2. 2.0 2.1 Kline JA et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J. Thromb. Haemost. 2004. 2:1247-55.
  3. Singh B et al. Pulmonary embolism rule-out criteria (PERC) in pulmonary embolism--revisited: a systematic review and meta-analysis. Emerg Med J 2013. 30:701-6.
  4. Penaloza A et al. Comparison of the unstructured clinician gestalt, the wells score, and the revised Geneva score to estimate pretest probability for suspected pulmonary embolism. Ann Emerg Med 2013. 62:117-124.e2.