Controversy over the role of fibrinolysis in patients with intermediate-risk pulmonary embolism (PE) has persisted because of the lack of adequately sized trials. The PEITHO study now allows a more precise estimate of the risk to benefit ratio of fibrinolysis in these patients. This trial enrolled patients with intermediate-risk PE who were randomized to receive heparin with either tenecteplase or placebo. Fibrinolysis was associated with a significant reduction in the combined end-point of death or hemodynamic decompensation, but also with a significant increase in the risk of major bleeding. The primary efficacy end-point occurred in 2.6 % of the patients in the tenecteplase group and in 5.6 % of the patients in the placebo group (OR, 0.44; 95 % CI, 0.23 to 0.87), conversely, major extracranial bleeding occurred in 6.3 % and 1.2 % in the tenecteplase and placebo groups, respectively (OR, 5.55; 95 % CI, 2.3 to 13.39) and stroke occurred in 2.4 % and in 0.2 % of the patients in the tenecteplase group and in the placebo group, respectively (OR, 12.10; 95 % CI, 1.57 to 93.39). No difference was observed for the risk of death alone and the risk of full-dose thrombolytic therapy outweighs its benefit in patients with intermediate-risk PE. Recent meta-analyses suggest that fibrinolysis may be associated with a slight reduction in overall mortality offset by an increase in major bleeding. Two pilot studies suggest that a reduced dose of fibrinolysis may produce significant hemodynamic improvement with a low risk of major bleeding. These options need to be evaluated in larger studies including patients with a higher risk of adverse outcome than those included in the PEITHO study.
Keywords: Bleeding; Fibrinolysis/Risk stratification; Mortality; Pulmonary embolism.