Should thrombolytic therapy be used in patients with pulmonary embolism?

More than thirty years have passed since streptokinase was first shown to dissolve pulmonary arterial thrombi and normalize pulmonary artery pressure in patients with acute pulmonary embolism (PE). Following the initial observations, a number of controlled clinical trials confirmed that treatment with streptokinase, urokinase or alteplase recombinant tissue plasminogen activator is superior to heparin alone in improving angiographic and hemodynamic parameters in these patients. At present, there is consensus that patients with massive PE presenting with overt right ventricular failure (clinical instability and cardiogenic shock) should promptly be treated with thrombolytic agents, since they are at a particularly high risk for death or life-threatening complications during the acute phase. At the other end of the clinical spectrum, thrombolysis for PE is not indicated in the absence of right ventricular dysfunction. In fact, the prognosis of patients with small pulmonary emboli (not affecting pulmonary artery pressure and right ventricular afterload), is excellent and, as a result, the bleeding risks of thrombolysis may outweigh the potential benefits of this treatment. Currently, the thrombolysis debate focuses on patients with submassive PE, i.e. those who present with signs of subclinical, impending right heart failure. Recently, a number of clinical studies demonstrated that these patients are also at risk for an adverse clinical outcome. Besides the established prognostic value of echocardiography, evidence is now accumulating that cardiac troponins and, possibly, pro-brain natriuretic peptide levels also may permit an early, reliable risk stratification of patients with PE and particularly help identify submassive PE in the presence of apparent clinical stability. Recently, the Management Strategies and Prognosis of Pulmonary Embolism-3 trial examined the effects of thrombolysis on the prognosis of patients with acute submassive PE. The study patients were randomly assigned to receive alteplase (100 mg over 2 hours) or placebo with concomitant heparin anticoagulation. Although in-hospital mortality was low in both the alteplase and the heparin-only group, this study showed for the first time that early treatment with alteplase can improve the clinical course of patients with acute submassive PE, and particularly reduce the need for emergency escalation of treatment. Importantly, no fatal or cerebral bleeding episodes were observed in the alteplase group. This fact indicates that use of thrombolysis in PE can be safe in patients who have no contraindications to this type of treatment. Based on these data, the indications for thrombolysis can be extended to include patients presenting with submassive PE.