Accelerated thrombolysis for pulmonary embolism: will clinical benefit be ULTIMAtely realized?

O ver the past 25 years, thrombolytic therapy has consistently demonstrated improvement in hemodynamic parameters in patients with pulmonary embolism (PE). 1 Clinically, although it results in reduced mortality in patients with massive PE, 2 thrombolytic therapy is not beneficial in unselected patients with PE. 3 Major societal guidelines support systemic throm-bolysis for massive PE and recommend catheter-based interventions for rescue therapy in centers with appropriate expertise. 4–6 For patients with submassive PE, selected guidelines suggest considering systemic thrombolysis in a limited population of patients with PE, 4,5 whereas others recommend against its use in these patients. 6 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 (compared with heparin alone) at the expense of a significant increase in major hemorrhage (including intracranial hemorrhage). This was particularly evident among elderly patients aged >75 years. 7 In the much smaller Tenecteplase or Placebo: Cardiopulmonary Outcomes At Three Months (TOPCOAT) study, 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 function, 6-minute walk distance >330 m, no dyspnea at rest, and no recurrent PE or deep vein thrombosis) was positive in the patients randomized to thrombolysis compared with the low-molecular-weight heparin patients. 8 Another small study comparing thrombolytic therapy with heparin alone demonstrated a decrease in the composite endpoint of death, recurrent venous thromboembolism, right ventricular dysfunction, and major hemorrhage at 6 months in the group randomized to thrombolytic therapy. 9 In the Moderate Pulmonary Embolism Treated with Thrombolysis (MOPPETT) trial, half-dose systemic thrombolytic therapy resulted in long-term reduction in the incidence of pulmonary hypertension compared with anticoagulation alone without excess bleeding. In this issue of Circulation, Kucher et al 11 compared the use of heparin and ultrasound accelerated thrombolysis (USAT) using the EkoSonic (EKOS, Bothell, WA) catheter with heparin alone in patients presenting with submassive PE. The primary outcome was change in the ratio of right ventricle/left ventricle size 24 hours after treatment, whereas the primary safety outcome was a composite of death, major and minor bleeding, recurrent venous thromboembolism, and serious adverse events at 90 days. The authors report a significant reduction in the primary outcome in the USAT group compared with the heparin group. …