Abstract: BACKGROUND: Hospitalization for low‐risk pulmonary embolism (PE) is common, expensive, and of questionable benefit. OBJECTIVE: The objective was to determine if low‐risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC). METHODS: Multicenter, open‐label randomized trial in low‐risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90‐day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality. RESULTS: Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of –28.8 hours (95% confidence interval [CI] = –42.55 to –15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = –46.97 to –3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = –0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = –$2,999 to –$2,151). CONCLUSIONS: Low‐risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days.
Objectives Traditionally, patients with pulmonary embolism ( PE) are admitted from the emergency department and treated with low-molecular-weight heparin followed by warfarin. Several studies now demonstrate that it is possible to identify low-risk PE patients that can safely be treated as outpatients. The advent of the direct-acting oral anticoagulants such as rivaroxaban has made it easier than ever to manage patients outside of the hospital. This article describes the design of a randomized controlled trial aimed at testing the hypothesis that low-risk PE patients can be safely and effectively managed at home using rivaroxaban, resulting in fewer days of hospitalization than standard-of-care treatment. Methods We have initiated a multicenter, open-label, randomized clinical trial in which low-risk adult PE patients (identified by the Hestia criteria) are randomized to outpatient management with oral rivaroxaban 15 mg twice daily for 21 days followed by 20 mg once daily for 90 days versus standard care, determined by the treating physician and based on local practices. The primary clinical endpoint will be the total number of inpatient hospital days (including the index admission) for venous thromboembolic or bleeding-related events during the first 30 days after randomization. A total of 150 subjects per group will provide 82% power to detect a difference of 1 day or greater in the primary outcome. Results Patient enrollment is ongoing at present in 45 of 60 planned sites. No interim analysis is planned and the study is being monitored by a data safety management board. Conclusions The MERCURY PE study is designed to test the hypothesis that outpatient management of low-risk PE patients with rivaroxaban reduces the number of hospitalization days from venous thromboembolism and bleeding compared with standard care. This article describes the rationale and methodology for this study.
The purpose of the study is to evaluate that low risk Pulmonary Embolism (PE) participants who are discharged from the Emergency Department (ED) to the home environment and treated with rivaroxaban as outpatients have fewer total days in the hospital for bleeding and/or venous thromboembolism (VTE) events through Day 30 compared to participants who are treated with initial hospitalization and standard-of-care.
CONTEXTE: Bien que les guides de pratique recommandent soins ambulatoires pour certains, patients hémodynamiquement stables présentant une embolie pulmonaire, la plupart des traitements en milieu hospitalier est actuellement basé. Nous avons cherché à évaluer la non-infériorité de soins ambulatoires par rapport aux soins hospitaliers.
MÉTHODES: Nous avons entrepris une étude ouverte, randomisée de non-infériorité d'essai de 19 services d'urgence en Suisse, en France, en Belgique et aux Etats-Unis. Nous assignés au hasard des patients en phase aiguë, une embolie pulmonaire symptomatique et d'un faible risque de mortalité (embolie pulmonaire classes de sévérité indice de risque I ou II) avec un ordinateur généré séquence de randomisation (blocs de 2-4) dans un rapport de 1:1 à ambulatoire initial (c.-à-congé de l'hôpital ≤ 24 h après la randomisation) ou un traitement avec hospitalisation énoxaparine sous-cutanée (≥ 5 jours), suivie par une anticoagulation orale (≥ 90 jours). Le critère principal était symptomatique, la thromboembolie veineuse récurrente dans les 90 jours; résultats de sécurité inclus saignements majeurs dans les 14 ou 90 jours et la mortalité dans les 90 jours. Nous avons utilisé une marge de non-infériorité de 4% pour une différence entre les patients hospitalisés et les groupes externes. Nous avons inclus tous les patients inscrits dans l'analyse principale, à l'exclusion des perdus de suivi. Ce procès est inscrit sur ClinicalTrials.gov, NCT00425542 nombre.
RÉSULTATS: Entre Février 2007 et Juin 2010, nous avons recruté 344 patients admissibles. Dans l'analyse principale, un (0,6%) de 171 patients ambulatoires développé thromboembolie veineuse récurrente dans les 90 jours, comparativement à aucun de 168 patients hospitalisés (95% de limite de confiance supérieure [UCL] 2,7%, p = 0,011). Un seul (0,6%) patients dans chaque groupe de traitement est décédé dans les 90 jours (95% UCL 2,1%, p = 0,005), et deux (1,2%) de 171 patients ambulatoires et hospitalisés eu aucun saignement majeur dans les 14 jours (95% UCL 3,6%, p = 0,031). En 90 jours, trois (1,8%) patients non hospitalisés, mais aucun des patients hospitalisés avaient développé des saignements majeurs (95% UCL 4,5%, p = 0,086). La durée moyenne de séjour était de 0,5 jours (SD 1,0) pour les patients externes et de 3,9 jours (SD 3,1) pour les patients hospitalisés.
Interprétation: Dans certaines patientes à faible risque d'embolie pulmonaire, les soins ambulatoires peuvent en toute sécurité et efficacement être utilisés à la place des soins hospitaliers.
FINANCEMENT: Swiss National Science Foundation, le Programme Hospitalier de Recherche Clinique, et le US National Heart, Lung, and Blood Institute. Sanofi-aventis a fourni l'approvisionnement en médicaments gratuitement dans les centres européens participants.
Hospitalization for low‐risk pulmonary embolism (PE) is common, expensive, and of questionable benefit.
OBJECTIVE:
The objective was to determine if low‐risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC).
METHODS:
Multicenter, open‐label randomized trial in low‐risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90‐day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality.
RESULTS:
Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of –28.8 hours (95% confidence interval [CI] = –42.55 to –15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = –46.97 to –3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = –0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = –$2,999 to –$2,151).
CONCLUSIONS:
Low‐risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days.
