Current literature on clinical controversies surrounding the use of thrombolytic agents in patients with intermediate-risk pulmonary embolism (PE) is reviewed.

PE is a major cause of morbidity and mortality. When used in conjunction with anticoagulation, thrombolysis has been shown to reduce hemodynamic decompensation in select patients, but thrombolytic therapy is associated with high risks of bleeding and intracranial hemorrhage and its role in treating patients with intermediate-risk PE remains controversial. In the PEITHO study, the largest trial to date involving only patients with intermediate-risk PE (n = 1,006), patients receiving the thrombolytic agent tenecteplase were significantly (p = 0.02) less likely than those receiving unfractionated heparin to develop the primary outcome, a composite of death from any cause and hemodynamic decompensation or collapse within 7 days. However, a meta-analysis of data from clinical trials of systemic thrombolytic therapy in intermediate-risk PE generally showed a lack of benefit in terms of all-cause mortality and long-term complications. Novel strategies for treatment of intermediate-risk PE, including low-dose thrombolysis and catheter-directed thrombolysis, are being investigated in an attempt to identify strategies that provide therapeutic outcomes equivalent to those provided by traditional thrombolytic modalities but with a decreased risk of bleeding.

The use of thrombolysis in the treatment of intermediate-risk PE is complicated by high rates of bleeding and should be limited to patients who clinically deteriorate rather than given as a standard-of-care treatment in this population. Data for low-dose thrombolysis remain limited.