Impact of the efficacy of thrombolytic therapy on the mortality of patients with acute submassive pulmonary embolism: a meta-analysis

J Thromb Haemost. 2014 Jul;12(7):1086-95. doi: 10.1111/jth.12608. Epub 2014 Jun 19.


Background: The efficacy of thrombolytic therapy in patients with submassive pulmonary embolism (PE) remains unclear. Previous meta-analyses have not separately reported the proportion of patients with submassive PE.

Objective: We assessed the effect of thrombolytic therapy on mortality, recurrent PE, clinical deterioration requiring treatment escalation and bleeding in patients with submassive PE.

Methods: The MEDLINE, EMBASE and Cochrane Library databases were searched to identify all relevant randomized controlled trials comparing adjunctive thrombolytic therapy with heparin alone as initial treatments in patients with acute submassive PE, and reported 30-day mortality or in-hospital clinical outcomes.

Results: A total of 1510 patients were enrolled in this meta-analysis. No significant differences were apparent in the composite endpoint of all-cause death or recurrent PE between the adjunctive thrombolytic therapy arm and the heparin-alone arm (3.1% vs. 5.4%; RR, 0.64 [0.32-1.28]; P = 0.2). Adjunctive thrombolytic therapy significantly reduced the incidence of the composite endpoint of all-cause death or clinical deterioration (3.9% vs. 9.4%; RR, 0.44; P < 0.001). There were no statistically significant associations for major bleeding when adjunctive thrombolytic therapy was compared with heparin therapy alone (6.6% vs. 1.9%; P = 0.2).

Conclusions: This meta-analysis shows that adjunctive thrombolytic therapy does not significantly reduce the risk of mortality or recurrent PE in patients with acute submassive PE, but that adjuvant thrombolytic therapy prevents clinical deterioration requiring the escalation of treatment in patients with acute submassive PE. Bleeding risk assessment might be the most successful approach for improving clinical outcomes and patient-specific benefit.

Keywords: heparin; mortality; prognosis; pulmonary embolism; thrombolytic therapy.

Publication types

  • Meta-Analysis

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use
  • Female
  • Fibrinolytic Agents / adverse effects*
  • Hemorrhage / chemically induced
  • Heparin / adverse effects*
  • Heparin / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Embolism / mortality*
  • Pulmonary Embolism / therapy*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Sensitivity and Specificity
  • Thrombolytic Therapy / methods*
  • Treatment Outcome


  • Anticoagulants
  • Fibrinolytic Agents
  • Heparin