Elsevier

The Lancet

Volume 378, Issue 9785, 2–8 July 2011, Pages 41-48
The Lancet

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Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial

https://doi.org/10.1016/S0140-6736(11)60824-6Get rights and content

Summary

Background

Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care.

Methods

We undertook an open-label, randomised non-inferiority trial at 19 emergency departments in Switzerland, France, Belgium, and the USA. We randomly assigned patients with acute, symptomatic pulmonary embolism and a low risk of death (pulmonary embolism severity index risk classes I or II) with a computer-generated randomisation sequence (blocks of 2–4) in a 1:1 ratio to initial outpatient (ie, discharged from hospital ≤24 h after randomisation) or inpatient treatment with subcutaneous enoxaparin (≥5 days) followed by oral anticoagulation (≥90 days). The primary outcome was symptomatic, recurrent venous thromboembolism within 90 days; safety outcomes included major bleeding within 14 or 90 days and mortality within 90 days. We used a non-inferiority margin of 4% for a difference between inpatient and outpatient groups. We included all enrolled patients in the primary analysis, excluding those lost to follow-up. This trial is registered with ClinicalTrials.gov, number NCT00425542.

Findings

Between February, 2007, and June, 2010, we enrolled 344 eligible patients. In the primary analysis, one (0·6%) of 171 outpatients developed recurrent venous thromboembolism within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2·7%; p=0·011). Only one (0·6%) patient in each treatment group died within 90 days (95% UCL 2·1%; p=0·005), and two (1·2%) of 171 outpatients and no inpatients had major bleeding within 14 days (95% UCL 3·6%; p=0·031). By 90 days, three (1·8%) outpatients but no inpatients had developed major bleeding (95% UCL 4·5%; p=0·086). Mean length of stay was 0·5 days (SD 1·0) for outpatients and 3·9 days (SD 3·1) for inpatients.

Interpretation

In selected low-risk patients with pulmonary embolism, outpatient care can safely and effectively be used in place of inpatient care.

Funding

Swiss National Science Foundation, Programme Hospitalier de Recherche Clinique, and the US National Heart, Lung, and Blood Institute. Sanofi-Aventis provided free drug supply in the participating European centres.

Introduction

Outpatient treatment of symptomatic deep vein thrombosis with low-molecular-weight heparin is regarded as usual care.1, 2, 3 Despite practice guideline recommendations to extend outpatient care to selected, haemodynamically stable patients with pulmonary embolism, management of symptomatic pulmonary embolism is predominantly inpatient based.4, 5, 6

Previous studies of outpatient care after pulmonary embolism were restricted by small sample sizes,7, 8, 9, 10, 11, 12 retrospective designs,13, 14, 15 and the absence of a randomised control group for comparison with inpatient care.7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 One randomised trial that compared medical outcomes of patients with pulmonary embolism who were assigned to inpatient versus outpatient care was stopped prematurely because mortality was unacceptably high in both treatment groups.19 We designed the Outpatient Treatment of Pulmonary Embolism (OTPE) trial to compare the effectiveness, safety, and efficiency of outpatient versus inpatient care for low-risk patients with acute, symptomatic pulmonary embolism as established with a validated clinical prognostic model.20

Section snippets

Study design and participants

We undertook an open-label, randomised, non-inferiority clinical trial at 19 emergency departments in Switzerland, France, Belgium, and the USA. Consecutive adults aged 18 years of age or older with acute, symptomatic, and objectively verified pulmonary embolism who were at low risk of death based on the pulmonary embolism severity index (risk classes I or II; table 1) were eligible to participate.20 The pulmonary embolism severity index is a clinical prognostic model that was derived and

Results

Between February, 2007, and June, 2010, we randomly allocated 172 eligible patients to the outpatient group and 172 to the inpatient group (figure; table 2). One outpatient and two inpatients were lost to follow-up and two inpatients withdrew consent during follow-up; therefore, we included 171 outpatients and 168 inpatients in the primary analysis.

Time from presentation to the emergency department until randomisation was much the same for outpatients and inpatients (13·9 h vs 13·3 h; p=0·24).

Discussion

Our multicentre trial of low-risk patients with acute, symptomatic pulmonary embolism showed that outpatient treatment with low-molecular-weight heparin is not inferior to inpatient treatment in terms of effectiveness and safety. Our findings are consistent with previous non-randomised studies and systematic reviews showing that outpatient care of pulmonary embolism is associated with low rates of recurrent VTE (0–6·2%), major bleeding (0–2·3%), and death (0–5·0%; panel).8, 9, 11, 12, 13, 14, 15

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