Survival Outcomes in Patients with Intermediate and High-Risk Pulmonary Embolism Treated with Low Molecular Weight or Unfractionated Heparin: Time to Start of Anticoagulant Therapy

Introduction

Venous Thromboembolism (VTE), including pulmonary embolism (PE), is the third most common cause of vascular disease related death in the United States. If left untreated, the mortality of PE is as high as 30%. The main-stay of treatment for PE involves anticoagulant therapy (AT), commonly with low molecular weight heparin (LMWH), or unfractionated heparin (UFH). Prior data has demonstrated a reduction in mortality with anticoagulant timing. In one study, 30-day all-cause mortality was lower in patients who achieved therapeutic AT, as defined by activated partial thromboplastin time (aPTT), within 24 hours of ER presentation. However, recent data demonstrated low numbers of patients with therapeutic range aPTT at 24 hours (< 30%). Thus, we aimed to assess the association between time to anticoagulant therapy from emergency room (ER) presentation and 30-day PE-associated mortality.

Methods

We performed a retrospective cohort study of patients at Barnes Jewish Hospital between January 2021 and April 2023 for which the Pulmonary Embolism Response Team (PERT) was activated. Patients with intermediate-low, intermediate-high, or massive (high-risk) PE who presented to the emergency department or urgent care facility with signs/symptoms concerning for PE were included. PE was objectively confirmed on imaging studies (CT or VQ Scan). Only patients initiated on UFH or LMWH were included. Patient demographic and hemodynamic data were collected on presentation. Those with low-risk PE, those started on an AT other than UFH/LMWH, and those who died prior to the start of AT were excluded. Time from ER presentation (as estimated by triage vital signs) to start of AT was calculated based on review of the Electronic Medical Record. The primary outcome was PE-associated mortality within 30 days. PE-associated mortality was defined as: deaths directly caused by PE, deaths caused by the treatment of PE, and multifactorial deaths with PE as a contributing illness. Using logistic regression, we calculated the association between each doubling of the time until AT was given and PE-associated mortality.

Results

A total of 184 patients met inclusion criteria, 138 patients with intermediate-risk PE and 46 with massive PE. 81% of patients received UFH (n = 149) and 19% received LMWH (n = 35). PE-associated mortality occurred in 5.1% (n = 7) of patients in the intermediate-risk group and 32.6% (n = 15) in the high-risk group. The average time from ER triage to start of AT was 5 hours in intermediate-risk patients who survived versus 8.1 hours in those who died. The average time from ER triage to start of AT was 5.3 hours in massive PE patients who survived versus 5.4 hours in those who died. After adjusting for massive PE classification and sPESI score, each doubling of time in delay of AT from ER presentation was associated with 1.27 increased odds of PE-associated death (odds ratio (OR) 1.27, 95% confidence interval (CI) 0.85, 1.89) (Table 1). The discrimination of the model was very good with a c-statistic of 0.83 for prediction of PE-associated 30-day mortality. When only analyzing patients with intermediate-risk PE, each doubling of time in delay of AT from ER presentation was associated with 2.72 increased odds of PE-associated death (OR 2.72, 95% CI 1.11, 6.78) (Table 1).

Conclusions

In patients with intermediate-risk or massive PE, each doubling of the time from patient presentation to the ER to start of anticoagulant therapy was associated with 1.27 increased odds in the risk of PE-associated 30-day mortality. This association was more pronounced in patients with intermediate-risk PE. Future efforts should be aimed at decreasing time from ER presentation to start of anticoagulant therapy in patients with PE such as through quality improvement projects and/or triage protocolization.