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

Kiser, Tyree H., PharmD1,2; Burnham, Ellen L., MD2,3; Clark, Brendan, MD2,3; Ho, P. Michael, MD, PhD2,4; Allen, Richard R., MS5; Moss, Marc, MD2,3; Vandivier, R. William, MD2,3

doi: 10.1097/CCM.0000000000003288
Clinical Investigations

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 < 0.01) and invasive ventilation (14.3% vs 28.5%; p < 0.01) less often, compared with full dose. After propensity matching (n = 548 per group), half-dose alteplase was associated with increased treatment escalation (53.8% vs 41.4%; p < 0.01), driven mostly by secondary thrombolysis (25.9% vs 7.3%; p < 0.01) and catheter thrombus fragmentation (14.2% vs 3.8%; p < 0.01). Hospital mortality was similar (13% vs 15%; p = 0.3). There was no difference in cerebral hemorrhage (0.5% vs 0.4%; p = 0.67), gastrointestinal bleeding (1.6% vs 1.6%; p = 0.99), acute blood loss anemia (6.9% vs 4.6%; p = 0.11), use of blood products (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.

1Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO.

2Colorado Pulmonary Outcomes Research Group (CPOR), University of Colorado Anschutz Medical Campus, Aurora, CO.

3Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.

4Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.

5Peak Statistical Services, Evergreen, CO.

*See also p. 1696.

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This study was conducted using academic enrichment funds from the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (to Dr. 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.

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