Study designs of evaluations included in the review
Randomised controlled trials (RCTs) were eligible for inclusion. Retrospective, non-randomised and quasi-randomised studies were excluded.
Specific interventions included in the review
Studies that compared thrombolytic therapy using urokinase, streptokinase or recombinant tissue-type plasminogen activator (rt-PA) with heparin were eligible for inclusion. Studies comparing two thrombolytic agents were excluded. The treatment regimens in the included studies were as follows.
For urokinase: 2,000 U/lb bolus then 2,000 U/lb per hour intravenously (i.v.) for 12 hours; 800,000 U/day i.v. for 72 hours; and 3,300,000 U i.v. for 12 hours.
For streptokinase: intrapulmonary, 600,000 U bolus then 100,000 U/hour for 72 hours; 250,000 U bolus then 100,000 U/hour for 72 hours; and 1,500,000 U i.v. over one hour.
For rt-PA: 40 to 80 mg i.v. over 90 minutes plus heparin; 0.6 mg/kg i.v. over 2 minutes; and 100 mg i.v. over 2 hours.
Participants included in the review
Studies of patients with acute PE were eligible for inclusion. All of the included studies excluded patients with contraindications to thrombolytic therapy. In all of the included studies, the patients had experienced symptoms consistent with acute PE at least 15 days previously. Some studies excluded patients in shock, while other studies did not; overall, only 5.2% of the participants presented in shock. Some studies only included patients with a study-defined extent of vascular obstruction. The participants ranged in age from 47 to 66 years and the proportion of males ranged from 27 to 100%.
Outcomes assessed in the review
Studies that assessed at least one of the following outcomes were eligible for inclusion: mortality, recurrence of PE, or major haemorrhage. Recurrence of PE had to be confirmed by a perfusion lung scan, pulmonary angiography or postmortem examination. Major haemorrhage was defined as intracranial or retroperitoneal haemorrhage or other bleeding requiring blood transfusion or surgery. The outcomes were assessed at the end of follow-up for each study. The duration of follow-up ranged from 3 to 14 days (median 7).
How were decisions on the relevance of primary studies made?
Two authors independently conducted the searches and selected the studies. Any disagreements were resolved through discussion with a third author.