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

Crit Care Med. 2018 Oct;46(10):1617-1625. doi: 10.1097/CCM.0000000000003288.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Coronary Circulation / drug effects
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / therapy
  • Pulmonary Ventilation*
  • Retrospective Studies
  • Tissue Plasminogen Activator / administration & dosage*
  • Treatment Outcome
  • Ventricular Function, Left / drug effects

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator