Clot Chronicles: The SLICE Trial — Significance of Pulmonary Embolism in COPD Exacerbations

Hello, everybody. My name is David Jiménez. I’m a respiratory physician at Ramón y Cajal Hospital in Madrid, Spain. Today on Clot Chronicles, we are going to discuss our recent study entitled, “Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes in Patients Hospitalized for COPD Exacerbation.” 

And the reason for this particular trial is that there were some studies suggesting that pulmonary embolism (PE) might be one of the frequent reasons for COPD exacerbation requiring a hospital admission – but these were prospective case-control studies, so we decided to perform a randomized controlled trial. 

In this trial, we enrolled patients with COPD exacerbations who required hospital admission, and we randomized these patients to standard management or to standard management plus an active search for PE. This active search for PE consisted of the use of D-dimer based on the high sensitivity of D-dimer, meaning that a negative D-dimer excludes the diagnosis of PE, followed by a CT angiogram for those patients with a positive D-dimer. 

In case we diagnosed PE, we started anticoagulation. In case we ruled out PE, we just used the standard therapy for a COPD exacerbation. So, we enrolled 746 patients who were randomized to one of these two strategies. The primary outcome for this particular trial was a composite of new or recurrent venous thromboembolism (VTE), readmission because of COPD exacerbation, and all-cause mortality during the first three months after randomization. 

In my opinion, the important result in this trial is that it was negative. In other words, there were no significant differences in the primary outcome for those patients who were randomized to an active search for PE, as compared to those patients who received usual care for their COPD exacerbation, nor were there significant differences for the secondary efficacy outcomes, which were new recurrent VTE, COPD readmissions, or all-cause mortality during the first 90 days of follow-up.

I think that there are a number of issues that might deserve some additional comment, and number one is that we enrolled patients without an initial clinical suspicion of PE. This means that for patients with COPD who arrive to the emergency department with suspicion of PE, you should proceed with a standard diagnostic algorithm to diagnose or rule out PE. Our patients hadn’t suspicion of PE and, in fact, these patients had low or intermediate clinical probability for PE, according to the Wells Score. 

Second, since we didn’t include patients with a high clinical probability for PE, we decided to use D-dimer for all these patients. D-dimer was able to exclude PE in one-fifth of the patients – in roughly half of the patients – and it was very sensitive, meaning that most of these patients didn’t have, in fact, PE. 

We performed a post hoc analysis. Instead of using a fixed cutoff for D-dimer, 500 nanograms per milliliter in most of the sites that participated in this trial, we used an age-adjusted D-dimer, and we were able to increase the number of patients without the need for a CT angiogram by around 15%. 

So in conclusion, our results suggest that we should not search for PE in most patients with COPD exacerbations who require hospital admission. Thank you very much.