Objective: To assess, by systematic review, the
efficacy and safety of recombinant tissue plasminogen activator (rt-PA)
in the treatment of lower extremity deep venous thrombosis (DVT). A
secondary objective is to assess the optimal dose and route of
administration of rt-PA.
Methods: Included studies
were randomized, controlled trials comparing rt-PA plus unfractionated
heparin (UFH) to UFH alone, rt-PA at different doses, or rt-PA by
different routes of administration in the treatment of DVT. Outcomes
had to be described in terms of percent change in venographic patency
for efficacy (>50% lysis) and in sufficient detail for complications
(major and minor hemorrhages and other). The search strategy included
searching electronic databases and contacting pharmaceutical agencies
and content experts. Study quality was assessed using the Jadad scale.
A threshold quality score was used to exclude trials.
Results: Five studies met the following inclusion criteria:
three comparing rt-PA plus UFH vs UFH alone (180 patients); one
comparing high-dose vs low-dose rt-PA (32 patients); and one comparing
systemic vs local administration of rt-PA (151 patients). In studies
comparing rt-PA vs placebo, patients assigned to rt-PA were more likely
to have > 50% lysis and complications (summary odds ratios [OR],
11.7; 95% confidence interval [CI], 2.61 to 52.5; and OR, 9.95; 95%
CI, 2.21 to 44.7, respectively). Major and intracerebral hemorrhages
were not significantly increased. One study comparing different doses
demonstrated that high-dose and low-dose rt-PA were equally efficacious
(OR, 0.88; 95% CI, 0.05 to 14.78). Local rt-PA was neither more
efficacious nor riskier than systemic rt-PA.
Conclusion: This systematic review does not support routine
use of rt-PA for DVT.