Randomized trials have clearly established that thrombolytic therapy increases bleeding in patients with acute myocardial infarction,140 but that evidence was indirect when applied to patients with PE. Since AT9, two additional small, randomized trials141,142 and a much larger trial143 have evaluated systemic thrombolytic therapy in about 1,200 patients with acute PE. The ndings of these new studies have been combined with those of earlier studies in a number of These new data, by reducing imprecision for estimates of ef cacy and safety and the overall risk of bias, have increased the quality of the evidence from low to moderate for recommendations about the use of systemic thrombolytic therapy in acute PE (Table 18, e-Table 18). Most of the new evidence comes from the Pulmonary Embolism Thrombolysis trial, which randomized 1,006 patients with PE and right ventricular dysfunction to tenecteplase and heparin or to heparin therapy alone The most notable ndings of this study were that thrombolytic therapy prevented cardiovascular collapse but increased major (including intracranial) bleeding; these bene ts and harms were nely balanced, with no convincing net bene t from thrombolytic therapy. An additional nding was that rescue thrombolytic therapy appeared to be of bene t in patients who developed cardiovascular collapse after initially being treated with anticoagulant therapy alone. 