Thrombolysis vs heparin in the treatment of pulmonary embolism: a clinical outcome-based meta-analysis

Arch Intern Med. 2002 Dec 9-23;162(22):2537-41. doi: 10.1001/archinte.162.22.2537.


Background: In patients with acute pulmonary embolism, thrombolysis results in a more rapid resolution of pulmonary emboli than heparin treatment. Whether this advantage results in an improved clinical outcome is unclear. We sought to perform a clinical outcome-based meta-analysis of studies comparing thrombolytic and heparin treatment in patients with pulmonary embolism.

Methods: Data concerning adverse outcome events (death, recurrent pulmonary embolism, and major bleeding events) were extracted from the identified randomized studies.

Results: A total of 56 (23.2%) of 241 patients treated with thrombolytic agents in 9 randomized trials experienced an adverse outcome event compared with 57 (25.9%) of 220 patients treated with heparin (relative risk [RR], 0.9; 95% confidence interval [CI], 0.57-1.32). In the thrombolysis group, 11 patients (4.6%) died compared with 17 (7.7%) in the heparin group (RR, 0.59; 95% CI, 0.27-1.25). Thirty-one patients (12.9%) undergoing thrombolysis had a major bleeding episode compared with 19 patients (8.6%) treated with heparin (RR, 1.49; 95% CI, 0.85-2.81). Five fatal bleeding episodes (2.1%) occurred in the thrombolysis group and none in the heparin group. Six studies provided data on recurrent pulmonary embolism. A recurrence occurred in 14 (6.6%) of 214 patients treated with thrombolytic agents and in 22 (10.9%) of 201 patients treated with heparin (RR, 0.60; 95% CI, 0.29-1.15). Recurrence and/or death occurred in 25 (10.4%) of 241 and in 38 (17.3%) of 220 patients treated with thrombolytic agents and heparin, respectively (RR, 0.55; 95% CI, 0.33-0.96; P =.03).

Conclusions: In patients with pulmonary embolism, thrombolysis had a lower composite end point of death/recurrence than heparin treatment. Excessive bleeding is the trade-off for improved efficacy. A comparative clinical outcome trial of thrombolysis and heparin treatment is warranted in patients with pulmonary embolism and selected for high risk of death and/or recurrence and low risk of bleeding.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Confidence Intervals
  • Female
  • Heparin / administration & dosage*
  • Heparin / adverse effects
  • Humans
  • Male
  • Odds Ratio
  • Prognosis
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / mortality*
  • Randomized Controlled Trials as Topic
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Survival Analysis
  • Thrombolytic Therapy / adverse effects
  • Thrombolytic Therapy / methods*
  • Treatment Outcome


  • Anticoagulants
  • Heparin