Bottom line: Thrombolytics provide clinical mortality benefit for massive PE with hemodynamic instability, and should be prescribed in hypotensive patients with massive PE. For submassive PE, based on a single RCT, thrombolytics did not reduce mortality, but did reduce the likelihood of later requiring thrombolytic therapy. Therefore, thrombolytic therapy remains an option in submassive PE, but guidelines generally recommend reserving this high risk intervention for patients with known mortality benefit.
Summary: Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002 Oct 10;347(15):1143-50. This is the only RCT that randomized patients with submassive PE. 256 patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dysfunction but without arterial hypotension or shock were randomized to receive either receive heparin plus 100 mg of alteplase or heparin plus placebo. Primary outcomes were in-hospital mortality or deterioration requiring additional treatment. RESULTS: Mortality was 3.4% in the heparin-plus-alteplase group and 2.2 % in the heparin-plus-placebo group, P=0.71.
Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association. Circulation. 2011 Mar 21. This scientific statement includes a review of data from 4 registries that tracks mortality rates in massive and sub-massive PEs. Data from the recently completed EMPEROR registry showed an in-hospital mortality rate of 3.0% for patients with submassive PE
The authors go on to state that even if additional thrombolytic therapy significantly reduced the mortality risk, it would be a small actual reduction given the relatively low mortality rate. The statement recommends assessing needs of individual patient and considering benefits in the context of potential harm.