Background: Patients with intermediate-risk pulmonary embolism (PE) have an elevated risk of adverse outcome. Early thrombolysis might improve the long-term prognosis of intermediate-risk PE.
Methods: A large multinational investigator-initiated and academically sponsored trial compared in a randomized (1:1) double-blind fashion thrombolysis with weight-adapted i.v. bolus tenecteplase versus placebo in normotensive patients with acute PE. Patients had right ventricular (RV) dysfunction on imaging plus a positive troponin I or T test. Both treatment groups received standard anticoagulation.
Results: A total of 1006 patients were enrolled at 76 sites in 13 countries. As previously reported, thrombolysis reduced (from 5.6% to 2.6%; P=0.015) seven-day mortality or hemodynamic collapse at a higher risk of haemorrhagic stroke (2.4% vs. 0.2%; P=0.003). All-cause 30-day mortality was 2.4% in the thrombolysis and 3.2% in the placebo arm. Six-month data were available for 486 (98.4%) and 474 (98.1%) patients, respectively.
Long-term follow-up was included in the third protocol amendment approved in 2012; 28 sites randomizing 667 patients participated. Outcome was assessed in 276/332 (83.1%) patients in the thrombolysis and 279/335 (83.3%) in the placebo arm. Mean follow-up duration was 41.6±15.7 months, and the death rates for 6-month survivors were 12.7% and 14.3%, respectively (P=0.568). Between day 30 and long-term follow-up, 53 of 58 (91%) of deaths in the thrombolysis and 50 of 54 (93%) in the placebo arm were due to underlying disease, mainly cancer. Persistent dyspnoea (mostly mild) or functional limitation was reported by 22.8% and 19.7%, respectively. Echocardiography did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension was confirmed in 4 (1.4%) and 6 (2.2%) cases respectively (P=0.740).
Conclusions: In a large randomized trial of patients with intermediate-risk PE, thrombolytic treatment did not affect long-term mortality, and it did not appear to reduce residual dyspnoea or RV dysfunction. In patients who survive the first 30 days after acute PE, late deaths are primarily due to underlying disease.