Early Anticoagulation is Associated with Reduced Mortality for Acute Pulmonary Embolism

Sean B. Smith, MD; Jeffrey B. Geske, MD; Jennifer M. Maguire, MD; Nicholas A. Zane, BA; Rickey E. Carter, PhD; Timothy I. Morgenthaler, MD, FCCP

Disclosures

CHEST. 2010;137(6):1382-1390. 

In This Article

Abstract and Introduction

Abstract

Background: Acute pulmonary embolism (PE) may be rapidly fatal if not diagnosed and treated. IV heparin reduces mortality and recurrence of PE, but the relationship between survival and timing of anticoagulation has not been extensively studied.
Methods: We studied 400 consecutive patients in the ED diagnosed with acute PE by CT scan angiography and treated in the hospital with IV unfractionated heparin from 2002 to 2005. Patients received heparin either in the ED or after admission. Time from ED arrival to therapeutic activated partial thromboplastin time (aPTT) was calculated. Outcomes included in-hospital and 30-day mortality, hospital and ICU lengths of stay, hemorrhagic events on heparin, and recurrent venous thromboembolism within 90 days.
Results: In-hospital and 30-day mortality rates were 3.0% and 7.7%, respectively. Patients who received heparin in the ED had lower in-hospital (1.4% vs 6.7%; P = .009) and 30-day (4.4% vs 15.3%; P < .001) mortality rates as compared with patients given heparin after admission. Patients who achieved a therapeutic aPTT within 24 h had lower in-hospital (1.5% vs 5.6%; P = .093) and 30-day (5.6% vs 14.8%; P = .037) mortality rates as compared with patients who achieved a therapeutic aPTT after 24 h. In multiple logistic regression models, receiving heparin in the ED remained predictive of reduced mortality, and ICU admission remained predictive of increased mortality.
Conclusions: We report an association between early anticoagulation and reduced mortality for patients with acute PE. We advocate further study with regard to comorbidities to assess the usefulness of modifications to hospital protocols.

Introduction

Acute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually.[1–3] As many as 95% of patients who die do so prior to diagnosis, with the majority of deaths occurring in untreated patients.[3–8] For patients who receive treatment, the 14- and 90-day mortality rates are approximately 10% and 20%, respectively.[5,9–11]

Barritt and Jordan[12] demonstrated that IV heparin improved overall survival for patients with PE. Others have confirmed these findings and have shown that therapeutic anticoagulation reduces rates of recurrent venous thromboembolism (VTE), which is believed to be a significant factor for mortality in patients with PE.[9,13,14] Indeed, Raschke et al[14] validated the weight-based heparin nomogram by demonstrating that it reduced recurrent VTE. Hull et al[15] found that achieving a therapeutic activated partial thromboplastin time (aPTT) within 24 h reduced the rates of VTE following acute deep vein thrombosis (DVT). Kline et al[16] reported that patients diagnosed with PE in the ED had improved outcomes as compared with those diagnosed after admission, but their study did not consider the timing of anticoagulation.

Guidelines recommend initiation of anticoagulation if clinical suspicion for PE is high, even prior to confirmatory testing.[3,17,18] Data are limited, however, that examine how the timing of anticoagulation relates to mortality, because early studies did not account for when or how quickly patients were anticoagulated. We examined how the timing of initial heparinization and achieving therapeutic anticoagulation relate to mortality in a cohort of patients who presented to an ED with acute, symptomatic PE.

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