Active search for pulmonary embolism does not change outcomes in patients with chronic obstructive pulmonary disease exacerbation

1. A randomized controlled trial of 746 patients found that there was no difference in composite outcomes for patients presenting with a chronic obstructive pulmonary disease (COPD) exacerbation who were actively assessed for pulmonary embolism (PE) compared to those who received usual care.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Pulmonary embolism (PE) is a potentially lethal condition which merits prompt investigation and management in the emergency department, particularly amongst patients with preexisting respiratory system disease. Some literature suggests that the incidence of pulmonary emboli (PE) may be increased amongst COPD patients. Patients may develop a PE for a multitude of reasons, many of which may cause or worsen a COPD flare. The Significance of PuLmonary EmbolIsm in COPD Exacerbations (SLICE) trial sought to evaluate whether actively searching for PE amongst patients presenting with a COPD exacerbation improved their overall health outcomes assessed at 90 days. 746 patients from several Spanish healthcare centres were included. Patients were eligible if they had a preexisting diagnosis of COPD and were hospitalized for an exacerbation without another primary respiratory illness. Patients in the intervention group (n = 370) underwent D-dimer testing in addition to usual care, while the control group (n = 367) had usual care only. The primary outcome was a composite of the following: symptomatic venous thromboembolism, readmission for COPD and death within 90 days of randomization. At 90 days, 29.7% of patients in the intervention group and 29.2% of patients in the control group experienced the primary outcome. There was no significant difference between groups. This RCT by Jiminez et al. demonstrated that investigating PE without a clinical indication is an inefficient use of time and resources in the initial management of patients hospitalized for a COPD exacerbation. One limitation of the study was the sample size, which was underpowered compared to what the authors had initially expected (intended sample size was 900 patients). Additionally, all patients in the control group and those in the intervention group without an initial diagnosis of PE received a prophylactic dose of low molecular weight heparin as a part of their initial COPD exacerbation management – this could have reduced the incidence of PE within 90 days of followup. Otherwise, this trial was conducted with rigorous methodology and contributes important findings to our understanding of COPD exacerbation management.

Click to read the study in JAMA

Relevant Reading: Incidence of pulmonary embolism during COPD exacerbation

In-Depth [randomized controlled trial]: This trial was conducted over a six year period, enrolling patients from 18 hospitals between September 2014 through July 2020. Exclusion criteria included a primary differential diagnosis of pulmonary embolism or another respiratory system disease (including pneumonia, pneumothorax); pregnant patients were also included. Patients were randomized on a 1:1 basis using permuted block randomization on a computer system. Missing data were not replaced and only one patient was lost to follow-up. Statistical calculations were performed with a type I error rate of 0.5. 186 (50.4%) of the patients in the intervention group had a positive D-dimer test; 97.3% of them went on to have a CTPA scan. 16 patients (8.8%) were found to have a PE and were treated with either low molecular weight heparin and Vitamin K antagonists (11/16), apixaban (4/16) or rivaroxaban (2/16). Amongst the control group, five patients (1.4%) underwent CTPA for clinical suspicion of PE; the diagnosis was confirmed in 3 patients. The overall rate of PE amongst the intervention group was thus 4.6% (95% confidence interval [95CI] 38-86%). The absolute risk difference with regards to the primary outcome between groups was 0.5% (95CI [-6.2%] to 7.3%). The relative risk of the primary outcome occurring in the intervention group compared to the control group was 1.02 (95CI 0.82 to 1.28), also indicating statistical nonsignificance. Finally, the hazard ratio for the composite outcome in the intervention group versus the control group was 1.0 (95CI 0.8-1.3). All-cause mortality occurred in 23 patients in the intervention group (6.2%) and 29 patients in the control group (7.9%) (risk difference, −1.7% [95% CI, −5.7% to 2.3%]). COPD was the most common cause of death. The most frequent secondary outcome in both groups was readmission because of COPD exacerbation, which occurred in 25.4% of the intervention group and 22.9% of the control group patients (relative risk 1.11 [0.86 to 1.43]). The median duration of hospitalization was 6 days in both groups.

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