Rule-Out Criteria Safely Reduced Testing for PE

Among very low-risk patients seen in emergency departments (EDs) with suspected pulmonary embolism (PE), the use of the PE rule-out criteria (PERC) did not result in more thromboembolic events during the following 3 months, a study found.

"In this cluster-randomized trial of 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 the course of 3 months. In addition, the PERC strategy was associated with a benefit in terms of reduced [computed tomography pulmonary angiography (CTPA)] use, ED length of stay, and likelihood of initial admission into hospital," the researchers write.

Yonathan Freund, MD, PhD, Sorbonne Université, and emergency department, Hôpital Universitaire Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, both in Paris, France, and colleagues report their findings in an article published online February 13 in JAMA.

The PERC rule comprises eight clinical criteria: arterial oxygen saturation of 94% or lower, pulse rate of 100/minute or higher, patient age of at least 50 years, unilateral leg swelling, hemoptysis, recent trauma or surgery, prior PE or deep venous thrombosis, and exogenous estrogen use.

The study included patients with suspected PE seen in 14 EDs in France, who were determined by the treating physician to have a lower than 15% clinical probability of PE. The researchers randomly assigned seven EDs to use the PERC strategy to evaluate patients for 6 months, followed by a 2-month washout period and then usual management for 6 months. The other seven EDs used usual management for the first 6 months and the PERC strategy for the second 6 months, with a 2-month washout period between. The study included 902 patients in the control group and 847 patients in the PERC group; the study ran from August 2015 through December 2016.

Among the PERC group, 459 (48%) patients had a PERC score of zero (PERC-negative). In these cases, the score alone was used to rule out PE and the patients did not undergo further testing. Patients with a positive PERC score underwent standard workup.

Overall, 40 (2%) patients received a PE diagnosis at the initial visit; 14 (1.5%) patients were in the PERC group compared with 26 (2.7%) in the control group (difference, 1.3%; 95% confidence interval [CI], −0.1% to 2.7%; P = .052). Among the 40 patients diagnosed with PE in the ED, 39 were diagnosed by CTPA and one with a pulmonary ventilation-perfusion scan. Six of the PEs diagnosed in the ED were subsegmental (PERC group, 1; control group, 5).

During follow-up, one patient in the PERC group was diagnosed with a thromboembolic event, which was the primary endpoint, compared with none in the control group (difference, 0.1%; one-sided 95% confidence interval, −∞% to 0.8%).

Lower CTPA Exposure With PERC Strategy

The study's secondary endpoints included the proportion of patients who underwent CTPA, the rate of CTPA-related adverse events that required therapeutic intervention within 24 hours, length of ED stay, rate of hospital admission or readmission, initiation of anticoagulation regimen, severe hemorrhage in patients receiving anticoagulation therapy, and all-cause mortality at 3 months.

Overall, 349 patients (18%) underwent CTPA, 39 of which were positive for PE. The resulting diagnostic yield for PE in the ED was 11% across both treatment groups. However, those in the PERC group were significantly less likely to undergo CTPA compared with the control group (13% vs 23%; difference, 9.7%; 95% confidence interval, 6.1% - 13.2%).

"The PERC strategy was...associated with an 8% absolute decrease in negative CTPA scanning.... These 8% of patients not subjected to negative CTPA scanning may benefit by avoiding harm," Jeffrey A. Kline, MD, from the Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, writes in an accompanying editorial.

"First, they avoided unnecessary radiation exposure, which may increase cancer risk, especially in the breast tissue of young women. The data from PROPER and other large studies from the United States show that approximately 25% of low-risk emergency care populations tested for PE are women younger than age 45 years.

"Second, these patients also avoid stress on the kidneys caused by intravenous iodinated contrast required for CTPA scanning; 14% of patients show evidence of acute kidney injury after CTPA. Third, these patients avoid risk for a false-positive PE diagnosis, which occurs in approximately 5% of all CTPA scans interpreted as positive for PE, owing to small or vaguely defined filling defects," Kline explains.

PERC Approach Noninferior for Other Secondary Outcomes

The median ED length of stay was significantly lower in the PERC group compared with the control group (4 hours and 36 minutes vs 5 hours and 14 minutes; P < .001). Hospital admission rates were lower in the PERC group than in the control group (13% vs 16%; difference, 3.3%; 95% confidence interval, 0.1% - 6.6%).

The rate of all-cause mortality at 3 months did not differ significantly between the PERC group (0.3%; three patients) compared with the control group (0.2%; two patients; P > .99). There was also no significant difference in 3-month hospital readmission rates (4% vs 7%; P = .051). The researchers saw no severe hemorrhage or severe adverse events subsequent to CTPA (0 in both groups).

Limitations of the study include a lower-than-estimated failure rate of the diagnosis strategy in the control group, which would make the sample size calculation inaccurate; possible inherent bias related to the study's cluster design; and the loss of 54 patients to follow-up, which may have altered the study's conclusions.

"As a pragmatic trial, the...protocol required no D-dimer or pulmonary vascular imaging for PERC-negative patients. Therefore, the protocol may have allowed PERC-negative patients with PE mild enough to not result in a subsequent visit to a health care professional to receive testing for PE, to be counted as a true negatives," Kline writes.

Freund reports nonfinancial support from Sanofi and lecture fees from Bristol-Myers Squibb and AstraZeneca outside the submitted work. One coauthor reports receipt of grants from AstraZeneca, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, sanofi-aventis, and Pfizer; and personal fees for board membership, consultancy services, or lecture fees from AstraZeneca, Bristol-Myers Squibb, Novartis, and sanofi-aventis outside the submitted work. The remaining authors have disclosed no relevant financial relationships. Kline reports receipt of grants from Roche Diagnostic, Mallinckrodt, Pfizer, Stago, and Janssen outside the submitted work.

JAMA. Published online February 13, 2018. Article full text, Editorial extract

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