Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial | Radiology | JAMA | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Konstantinides  SV, Torbicki  A, Agnelli  G,  et al 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.  Eur Heart J. 2014;35(43):3033-3069, 3069a-3069k..PubMedGoogle ScholarCrossref
van Belle  A, Büller  HR, Huisman  MV,  et al; Christopher Study Investigators.  Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography.  JAMA. 2006;295(2):172-179.PubMedGoogle ScholarCrossref
Wiener  RS, Schwartz  LM, Woloshin  S.  Time trends in pulmonary embolism in the United States: evidence of overdiagnosis.  Arch Intern Med. 2011;171(9):831-837.PubMedGoogle ScholarCrossref
Wiener  RS, Schwartz  LM, Woloshin  S.  When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found.  BMJ. 2013;347(jul02):f3368-f3368..PubMedGoogle ScholarCrossref
Kline  JA, Mitchell  AM, Kabrhel  C, Richman  PB, Courtney  DM.  Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.  J Thromb Haemost. 2004;2(8):1247-1255.PubMedGoogle ScholarCrossref
Pauker  SG, Kassirer  JP.  The threshold approach to clinical decision making.  N Engl J Med. 1980;302(20):1109-1117.PubMedGoogle ScholarCrossref
Singh  B, Mommer  SK, Erwin  PJ, Mascarenhas  SS, Parsaik  AK.  Pulmonary embolism rule-out criteria (PERC) in pulmonary embolism–revisited: a systematic review and meta-analysis.  Emerg Med J. 2012;30(9):701-706..PubMedGoogle ScholarCrossref
Lapner  ST, Kearon  C.  Diagnosis and management of pulmonary embolism.  BMJ. 2013;346:f757.PubMedGoogle ScholarCrossref
Campbell  MK, Piaggio  G, Elbourne  DR, Altman  DG; CONSORT Group.  CONSORT 2010 statement: extension to cluster randomised trials.  BMJ. 2012;345:e5661.PubMedGoogle ScholarCrossref
Penaloza  A, Verschuren  F, Meyer  G,  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(2):117-124.e2.PubMedGoogle ScholarCrossref
Righini  M, Van Es  J, Den Exter  PL,  et al.  Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study.  JAMA. 2014;311(11):1117-1124.PubMedGoogle ScholarCrossref
Righini  M, Le Gal  G, Aujesky  D,  et al.  Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial.  Lancet. 2008;371(9621):1343-1352.PubMedGoogle ScholarCrossref
Righini  M, Aujesky  D, Roy  PM,  et al.  Clinical usefulness of D-dimer depending on clinical probability and cutoff value in outpatients with suspected pulmonary embolism.  Arch Intern Med. 2004;164(22):2483-2487.PubMedGoogle ScholarCrossref
Perrier  A, Roy  P-M, Aujesky  D,  et al.  Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study.  Am J Med. 2004;116(5):291-299.PubMedGoogle ScholarCrossref
Freund  Y, Rousseau  A, Guyot-Rousseau  F,  et al.  PERC rule to exclude the diagnosis of pulmonary embolism in emergency low-risk patients: study protocol for the PROPER randomized controlled study.  Trials. 2015;16:537.PubMedGoogle ScholarCrossref
Kline  JA, Courtney  DM, Kabrhel  C,  et al.  Prospective multicenter evaluation of the pulmonary embolism rule-out criteria.  J Thromb Haemost. 2008;6(5):772-780.PubMedGoogle ScholarCrossref
Hugli  O, Righini  M, Le Gal  G,  et al.  The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism.  J Thromb Haemost. 2011;9(2):300-304.PubMedGoogle ScholarCrossref
Righini  M, Le Gal  G, Perrier  A, Bounameaux  H. More on: clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.  J Thromb Haemost. 2005;3(1):188-191.PubMedGoogle ScholarCrossref
Penaloza  A, Kline  J, Verschuren  F,  et al.  European and American suspected and confirmed pulmonary embolism populations: comparison and analysis.  J Thromb Haemost. 2012;10(3):375-381.PubMedGoogle ScholarCrossref
Pernod  G, Caterino  J, Maignan  M, Tissier  C, Kassis  J, Lazarchick  J; DIET study group.  D-Dimer use and pulmonary embolism diagnosis in emergency units: why is there such a difference in pulmonary embolism prevalence between the United States of America and countries outside USA?  PLoS One. 2017;12(1):e0169268.PubMedGoogle ScholarCrossref
Penaloza  A, Verschuren  F, Dambrine  S, Zech  F, Thys  F, Roy  P-M.  Performance of the Pulmonary Embolism Rule-out Criteria (the PERC rule) combined with low clinical probability in high prevalence population.  Thromb Res. 2012;129(5):e189-e193.PubMedGoogle ScholarCrossref
Tan  S, Haramati  LB.  Overdiagnosis versus misdiagnosis of pulmonary embolism.  AJR Am J Roentgenol. 2016;206(4):W59.PubMedGoogle ScholarCrossref
Sheh  SH, Bellin  E, Freeman  KD, Haramati  LB.  Pulmonary embolism diagnosis and mortality with pulmonary CT angiography versus ventilation-perfusion scintigraphy: evidence of overdiagnosis with CT?  AJR Am J Roentgenol. 2012;198(6):1340-1345.PubMedGoogle ScholarCrossref
Raja  AS, Ip  IK, Prevedello  LM,  et al.  Effect of computerized clinical decision support on the use and yield of CT pulmonary angiography in the emergency department.  Radiology. 2012;262(2):468-474.PubMedGoogle ScholarCrossref
Mongan  J, Kline  J, Smith-Bindman  R.  Age and sex-dependent trends in pulmonary embolism testing and derivation of a clinical decision rule for young patients.  Emerg Med J. 2015;32(11):840-845.PubMedGoogle ScholarCrossref
Kline  JA, Stubblefield  WB.  Clinician gestalt estimate of pretest probability for acute coronary syndrome and pulmonary embolism in patients with chest pain and dyspnea.  Ann Emerg Med. 2014;63(3):275-280.PubMedGoogle ScholarCrossref
Penaloza  A, Soulié  C, Moumneh  T,  et al.  Pulmonary embolism rule-out criteria (PERC) rule in European patients with low implicit clinical probability (PERCEPIC): a multicentre, prospective, observational study.  Lancet Haematol. 2017;4(12):e615-e621.PubMedGoogle ScholarCrossref
Stein  PD, Goodman  LR, Hull  RD, Dalen  JE, Matta  F.  Diagnosis and management of isolated subsegmental pulmonary embolism: review and assessment of the options.  Clin Appl Thromb Hemost. 2012;18(1):20-26.PubMedGoogle ScholarCrossref
Kruip  MJHA, Leclercq  MGL, van der Heul  C, Prins  MH, Büller  HR.  Diagnostic strategies for excluding pulmonary embolism in clinical outcome studies: a systematic review.  Ann Intern Med. 2003;138(12):941-951.PubMedGoogle ScholarCrossref
Dronkers  CEA, van der Hulle  T, Le Gal  G,  et al; Subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease.  Towards a tailored diagnostic standard for future diagnostic studies in pulmonary embolism: communication from the SSC of the ISTH.  J Thromb Haemost. 2017;15(5):1040-1043.PubMedGoogle ScholarCrossref
Original Investigation
February 13, 2018

Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial

Author Affiliations
  • 1Sorbonne Université, INSERM UMRS 1166, IHU ICAN, Paris, France
  • 2Emergency Department, Hôpital Universitaire Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
  • 3Clinical Research Platform (URC-CRC-CRB), AP-HP Hôpital Saint-Antoine, Paris, France
  • 4Emergency Department, Hôpital Avicenne, APHP, Bobigny, France
  • 5Emergency Department, Hôpital Saint-Antoine, APHP, Paris, France
  • 6Emergency Department, Hôpital Européen Georges Pompidou, APHP, Paris, France
  • 7Université Toulouse III Paul Sabatier, INSERM UMR 1027, CHU Toulouse, Toulouse, Emergency Department, Toulouse, France
  • 8Université Paris Descartes, INSERM UMR970, APHP, Emergency Department, Hôpital Cochin, Paris, France
  • 9Emergency Department, Hôpital Tenon, APHP, Paris, France
  • 10Emergency Department, Hôpital Lariboisière, APHP, Paris, France
  • 11Université Bourgogne Franche-Comté, Emergency Department, CHRU Minjoz, Besançon, France
  • 12Université Claude Bernard Lyon1, HESPER EA 7425, Hospices Civils de Lyon, Emergency Department, Hôpital Edouard Herriot, Lyon, France
  • 13Emergency Department, Hôpital Ambroise-Paré, APHP, Boulogne, France
  • 14Emergency Department, Hôpital Bichat, APHP, Paris, France
  • 15Université Paris Est, INSERM U955, APHP, Emergency Department, Hôpital Henri Mondor, Créteil, France
  • 16Emergency Department, Hôpital Saint Camille, Bry sur Marne, France
  • 17Emergency Department, Barts Health NHS Trust, London, United Kingdom
JAMA. 2018;319(6):559-566. doi:10.1001/jama.2017.21904
Key Points

Question  Does use of the pulmonary embolism rule-out criteria (PERC) in emergency department patients with low clinical probability of pulmonary embolism (PE) safely exclude the diagnosis of PE?

Findings  In this cluster-randomized crossover noninferiority trial that included 1916 patients with very low clinical probability of PE, the 3-month risk of a thromboembolic event when using a PERC strategy compared with a conventional strategy was 0.1% vs 0%, a difference that met the noninferiority criterion of 1.5%.

Meaning  In emergency department patients at very low risk of PE, the use of a PERC-based strategy did not lead to an inferior rate of subsequent thromboembolic events.


Importance  The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial.

Objective  To prospectively validate the safety of a PERC-based strategy to rule out PE.

Design, Setting, and Patients  A crossover cluster–randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016.

Interventions  Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative.

Main Outcomes and Measures  The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission.

Results  Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, −0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, −∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, −10% [95% CI, −13% to −6%]; P < .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%]).

Conclusions and Relevance  Among very low-risk patients with suspected PE, randomization to a PERC strategy vs conventional strategy did not result in an inferior rate of thromboembolic events over 3 months. These findings support the safety of PERC for very low-risk patients presenting to the emergency department.

Trial Registration  clinicaltrials.gov Identifier: NCT02375919