Accelerated Thrombolysis for Pulmonary Embolism: Will Clinical Benefit Be ULTIMAtely Realized?
Over the past 25 years, thrombolytic therapy has consistently demonstrated improvement in hemodynamic parameters in patients with pulmonary embolism (PE)1. Clinically, while resulting in reduced mortality in patients with massive PE2 thrombolytic therapy is not beneficial in unselected PE patients3. Major societal guidelines support systemic thrombolysis for massive PE, and recommend catheter-based interventions for rescue therapy in centers with appropriate expertise4-6. For patients with submassive PE, selected guidelines suggest considering systemic thrombolysis in a limited population of PE patients4,5, while others recommend against its use in these patients6. Recently, several studies have addressed thrombolytic therapy in patients with submassive PE. The Pulmonary Embolism International Thrombolysis (PEITHO) trial reported a substantial reduction in the combined endpoint of early mortality or hemodynamic collapse in patients receiving systemic thrombolysis (as compared to heparin alone) at the expense of a significant increase in major hemorrhage (including intracranial hemorrhage). This was particularly evident among elderly patients over the age of 757. In the much smaller TOPCOAT study (Tenecteplase or Placebo: Cardiopulmonary Outcomes At Three Months), which was terminated prematurely, the composite primary outcome (5 day survival to hospital discharge without shock, intubation, or major hemorrhage; 90 day rate of normal right ventricular (RV) function, 6 minute walk distance>330 meters, no dyspnea at rest, and no recurrent PE or deep vein thrombosis) was positive in the patients randomized to thrombolysis as compared to the low molecular weight heparin patients8. Another small study comparing thrombolytic therapy to heparin alone demonstrated a decrease in the composite endpoint of death, recurrent venous thromboembolism, RV dysfunction and major hemorrhage at 6 months in the group randomized to thrombolytic therapy9. In the MOPPETT trial, half-dose systemic thrombolytic therapy resulted in long-term reduction in the incidence of pulmonary hypertension compared to anticoagulation alone without excess bleeding10.
- Received November 9, 2013.
- Accepted November 12, 2013.