Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism

TLDR

The role of fibrinolytic therapy in intermediate‑risk pulmonary embolism is controversial. In a randomized, double‑blind trial of 1006 normotensive intermediate‑risk pulmonary embolism patients, investigators compared tenecteplase plus heparin with placebo plus heparin, enrolling those with right‑ventricular dysfunction and troponin elevation, and assessed death or hemodynamic decompensation within 7 days as the primary outcome. Tenecteplase reduced the composite endpoint of death or hemodynamic decompensation (2.6% vs 5.6%, OR 0.44, P = 0.02) but markedly increased major extracranial bleeding (6.3% vs 1.2%, P < 0.001) and stroke (2.4% vs 0.2%, P = 0.003). The study was funded by the Programme Hospitalier de Recherche Clinique in France and registered under PEITHO EudraCT 2006‑005328‑18 and ClinicalTrials.gov NCT00639743.

Abstract

The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial.In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization.Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42).In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).