Half-Dose Versus Full-Dose Alteplase for Treatment of Pulmonary Embolism

Objectives: Recent evidence suggests that half-dose thrombolysis for pulmonary embolism may provide similar efficacy with reduced bleeding risk compared with full-dose therapy, but comparative studies are lacking. We aimed to evaluate the effectiveness and safety of half-dose versus full-dose alteplase for treatment of pulmonary embolism. Design: A retrospective cohort study comparing outcomes in patients receiving half-dose (50 mg) versus full-dose (100 mg) alteplase for pulmonary embolism. We used propensity score matching and sensitivity analyses to address confounding and hospital-level clustering. Setting: Data from 420 hospitals obtained from the Premier Healthcare Database between January 2010 and December 2014. Subjects: Adult critically ill patients with acute pulmonary embolism treated with IV alteplase therapy. Interventions: None. Measurements and Main Results: This study included 3,768 patients: 699 (18.6%) in the half-dose and 3,069 (81.4%) in the full-dose group. At baseline, patients receiving half-dose alteplase required vasopressor therapy (23.3% vs 39.4%; p 0.05 for all), or documented fibrinolytic adverse events (2.6% vs 2.8%; p = 0.82). Conclusions: Compared with full-dose alteplase, half-dose was associated with similar mortality and rates of major bleeding. Treatment escalation occurred more often in half-dose–treated patients. These results question whether half-dose alteplase provides similar efficacy with improved safety, and highlights the need for further study before use of half-dose alteplase therapy can be routinely recommended in patients with pulmonary embolism. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (https://ift.tt/29S62lw). This study was conducted using academic enrichment funds from the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (to Ms. Kiser), and in part by R01HL129938 (to Dr. Vandivier). Presented, in part, as an abstract at the Society of Critical Care Medicine Annual Congress, Honolulu, HI, January 22, 2017 (Society of Critical Care Medicine Silver medal research abstract award recipient). Dr. Ho received funding from Janssen and the American Heart Association, and he disclosed government work. Dr. Moss received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Ty.Kiser@ucdenver.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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