The Pulmonary Embolism Rule-Out Criteria have been both lauded and maligned, depending on which day the literature is perused. There are case reports of large emboli in patients who are PERC-negative, as well as reports of PE prevalence as high as 5% – in contrast to its derivation meeting the stated point of equipoise at <1.8%. So, the goal here is to be the prospective trial to end all trials and most accurately describe the impact of PERC on practice and outcomes.
This is a cluster-randomized trial across 14 Emergency Departments across France. Centers were randomized to either a PERC-based work-up strategy for PE, or “conventional” in which virtually every patient considered for PE was tested using D-dimer. Interestingly, these 14 centers also crossed-over to the alternative algorithm approximately halfway through the study period, so every ED was exposed to both interventions – some of which used PERC first, and vice versa.
Overall, they recruited 1,916 patients across the two enrollment periods, and these authors focused on the 1,749 who received per-protocol testing and were not lost to follow-up. The primary outcome was any new diagnosis of venous thromboembolism at 3 month follow-up. This was their measure of, essentially, clinically important missed VTE upon exiting their algorithm. The headline results here were, in their per-protocol population, that 1 patient was diagnosed with VTE in follow-up in the PERC group compared with none in the control cohort. This met their criteria for non-inferiority, and, just at face value, the PERC-based strategy is clearly reasonable. There were 48 patients lost to follow-up, however, but given the overall prevalence of PE in this population, it is unlikely these lost patients would have affected the overall results.
There are a few interesting bits to work through from the characteristics of the study cohort. The vast majority of patients considered for the diagnosis of PE were “low risk” by either Wells or simplified Revised Geneva Score. However, 91% of those in the PERC cohorts were “low risk”, as compared to 78% in the control cohort – which, considering the structure of this trial, seems unlikely to have occurred by chance alone. In the PERC cohort, about half failed to meet PERC and these patients – plus a few protocol violations – moved forward with D-dimer testing. In the conventional cohort, 99% were tested with D-dimer in accordance with their algorithm.
There were then, again, more odd descriptive results at this point. The results of the D-dimer testing (≥0.5 µg/mL) were positive in 343 of the PERC cohort and 471 of the controls. However, physicians only moved forward with CTPA in 38% of the PERC cohort and 46% of the conventional cohort. It is left entirely unaddressed why patients entered a PE rule-out pathway and ultimately never received a definitive imaging test after a D-dimer above threshold. For what it’s worth, then, the fewer patients undergoing evaluation for PE in the PERC cohort led to fewer diagnoses of PE, fewer downstream hospital admissions and anticoagulants, and their ED length of stay was shorter. The absolute numbers are small, but patients in the control cohort undergoing CTPA were more likely to have subsegmental PEs (5 vs. 1), which, again, ought to generally make sense.
So, finally, what is the takeaway here? Should you use a PERC-based strategy? As usual, the answer is: it depends. Firstly, it is almost certainly the case the PERC-based algorithm is safe to use. Then, if your current approach is to carpet bomb everyone with D-dimer and act upon it, yes, you may see dramatic improvements in ED processes and resource utilization. However, as we see here, the prevalence of PE is so low, strict adherence to a PERC-based algorithm is still too clinically conservative. Many elevated D-dimers did not undergo CTPA in this study – and, with three month follow-up, they obviously did fine. Frankly, given the shifting gestalt relating to the work-up of PE, the best cut-off is probably not PERC, but simply stopping the work-up of most patients not intermediate- or high-risk.
“Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial”