Normotensive patients with intermediate-risk pulmonary embolism (PE), indicated by the presence of acute right ventricular (RV) dysfunction and myocardial injury, have an elevated risk of adverse outcome. It remains unclear whether fibrinolysis can improve the long-term prognosis of intermediate-risk PE.

Methods and results: The Pulmonary EmbolIsm THrOmbolysis trial (PEITHO) is an investigator-initiated, academic-sponsor, prospective, multicenter, international, randomized (1:1), double-blind comparison of thrombolysis with weight-adapted i.v. bolus tenecteplase versus placebo in normotensive patients with confirmed acute PE. Patients had RV dysfunction on echocardiography or computed tomography, plus a positive troponin I or T test. Both treatment groups received standard anticoagulation. The primary efficacy outcome was death from any cause or haemodynamic collapse within 7 days of randomization. A total of 1006 patients were enrolled at 76 sites in 13 countries. The results regarding the primary efficacy outcome have been presented. Briefly, thrombolytic therapy reduced (from 5.6% to 2.6%; P=0.015) the primary end point at the cost of an increased risk of major haemorrhage, particularly haemorrhagic stroke (2.4% versus 0.2%; P=0.003). Death rates at 30 days were 2.4% and 3.2% respectively.

Six-month (180-day) follow-up data were available for 486 patients (98.4%) of the tenecteplase and 474 (98.1%) of the placebo (heparin-only) arm. During this period, a total of 35 patients (7.0%) in the tenecteplase and 30 (6.1%) in the placebo group died (P=0.566). Six-month death rates for patients who survived the first 30 days after randomization were 4.7% and 3.0% respectively (P=0.152). Most deaths occurring within the first 30 days resulted from acute PE or the complications of treatment; between day 30 and day 180, 16/23 (70%) of deaths in the tenecteplase and 12/14 (86%) in the placebo arm were due to the underlying disease, particularly cancer. Residual dyspnoea at 6 months was assessed in 71.2% of the patients, 45.2%, 20.4%, 4.8% and 0.6% were in NYHA stage I, II, III and IV, respectively, without difference between the groups. In 51% of the patients, follow-up echocardiography was performed without significant differences in the rates of residual pulmonary hypertension or RV dysfunction.

Conclusions: In a large randomized trial of patients with intermediate-risk PE, thrombolytic treatment did not affect 6-month mortality, residual dyspnea and RV dysfunction. In patients who survive the first 30 days after acute PE, late deaths are primarily due to underlying disease.