Franck Verschuren

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

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.

Cardiac biomarkers for risk stratification in non-massive pulmonary embolism: a multicenter prospective study

Summary.  Background: Troponins (cTnI and cTnT), N‐terminal pro‐Brain Natriuretic Peptide (NT‐proBNP), myoglobin, heart‐type fatty acid‐binding protein (H‐FABP) and fibrin D‐Dimer are emergent candidates for risk stratification in pulmonary embolism (PE). Objective: To compare the respective prognostic values of biomarker with non‐massive PE to predict an adverse outcome at 3 months. Patients/Methods: One hundred and forty‐six consecutive patients with non‐massive PE were included in this multicenter prospective study. The combined outcome consisted of intensive care monitoring on admission, death or hospitalization attributable to either a PE‐related complication [defined by PE/deep vein thrombosis (DVT) relapse or major bleeding under anticoagulation] or to dyspnoea with or without chest pain during follow‐up. Results: The outcome was met in 12% of patients. In univariate analysis, a NT‐proBNP level above 300 pg/ml was the strongest predictor of unfavorable outcome with an odds ratio (OR) of 15.8 [95% confidence interval (CI): 2.05–122). ORs for the other variables were: 8.0 for D‐dimer >2000 ng/ml (95% CI: 1.1–64), 4.7 for H‐FABP >6ng/ml (95% CI:1.5–14.8), 3.5 for cTnI >0.09 ng/ml (95% CI:1.2–9.7), 3.4 for myoglobin >70 ng/ml (95% CI:0.9–12.2). Receiver operating curve (ROC) analysis indicated that NT‐proBNP was the best predictor [area under the curve (AUC) 0.84; 95%CI: 0.76–0.92; P < 0.0001] with a negative predictive value of 100% (95% CI: 91–100) at 300 pg/ml. At that cut‐off, the true negative rate for NT‐proBNP was 40%. In multivariate analysis, NT‐proBNP was the only significant independent predictors. Conclusions: NT‐proBNP appears to be a good risk stratification marker in identifying low‐risk patients with non‐massive PE who could be treated in an outpatient setting.

The Simplified Pulmonary Embolism Severity Index (PESI): validation of a clinical prognostic model for pulmonary embolism.

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Complete venous ultrasound in outpatients with suspected pulmonary embolism

Summary.  Background: Compression ultrasonography (US) confined to the proximal veins is usually performed to detect deep vein thrombosis (DVT) in patients with suspected pulmonary embolism (PE). Recent studies suggested a limited yield of proximal US when multislice computed tomography (MSCT) was used. Objectives: To assess whether performing an additional distal vein US would increase the diagnostic yield of the test. Patients and methods: Data of 855 consecutive outpatients included in a multicenter randomized controlled trial were analyzed. Patients were investigated by a sequential diagnostic strategy including clinical probability assessment, D‐dimer measurement, proximal US and MSCT. Proximal US was completed by an examination of the distal veins, the result of which was not disclosed to the physician in charge of the patient. Results: US was positive in 21% of patients, of whom 10% (53/541) had proximal DVT and 11% (59/541) isolated distal DVT. Of the 59 patients with distal DVT, 21 (36%) had no PE on MSCT. Twenty of those 21 patients were not given anticoagulant therapy and had an uneventful follow‐up. The diagnostic performance of distal US for the diagnosis of PE was as follows: sensitivity 22% [95% confidence interval (CI) 17–29]; specificity 94% (95% CI 91–96); positive likelihood ratio 3.9 (95% CI 2.4–6.4). Conclusions: In patients with suspected PE, distal US has limited diagnostic performance, and its additional use only modestly increases the yield of US. Moreover, it carries a high false‐positive rate, impeding the use of distal US as a confirmatory test for PE.

Is atrial fibrillation associated with pulmonary embolism

Summary.  Background: A pulmonary embolism (PE) is thought to be associated with atrial fibrillation (AF). Nevertheless, this association is based on weak data. Objectives: To assess whether the presence of AF influences the clinical probability of PE in a cohort of patients with suspected PE and to confirm the association between PE and AF. Patients/methods: We retrospectively analyzed the data from two trials that included 2449 consecutive patients admitted for a clinically suspected PE. An electrocardiography (ECG) was systematically performed and a PE was diagnosed by computer tomography (CT). The prevalence of AF among patients with or without a PE was compared in a multivariate logistic regression model. Results: The prevalence of PE was 22.8% (519/2272) in patients without AF and 18.8% (25/133) in patients with AF (P = 0.28). After adjustment for confounding factors, AF did not significantly modify the probability of PE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.42–1.11). However, when PE suspicion was based on new‐onset dyspnea, AF significantly decreased the probability of PE (OR 0.47, 95% CI 0.26–0.84). If isolated chest pain without dyspnea was the presenting complaint, AF tended to increase the probability of PE (OR 2.42, 95% CI 0.97–6.07). Conclusions: Overall, the presence of AF does not increase the probability of PE when this diagnosis is suspected. Nevertheless, when PE suspicion is based on new‐onset dyspnea, AF significantly decreases the probability of PE, as AF may mimic its clinical presentation. However, in patients with chest pain alone, AF tends to increase PE probability.

Prognostic value of the Geneva prediction rule in patients in whom pulmonary embolism is ruled out.

Abstract.  Bertoletti L, Le Gal G, Aujesky D, Roy P‐M, Sanchez O, Verschuren F, Bounameaux H, Perrier A, Righini M. (University of Geneva, Geneva, Switzerland; Université De Saint‐Etienne, Jean Monnet, Saint‐Etienne; Brest University Hospital, Brest, France; Bern University Hospital, Bern, Switzerland; Angers University Hospital, Angers; Paris Descartes University, Paris, France; Saint‐Luc University Hospital, Bruxelles, Belgium; and University of Geneva, Geneva, Switzerland). Prognostic value of the Geneva prediction rule in patients in whom pulmonary embolism is ruled out. J Intern Med 2011; 269: 433–440.