Thrombolytic therapy for thrombotic diseases has been in study and use for more than 5 decades. More than 4 decades ago, Arthur Sasahara, MD, reported the benefit of catheter-based urokinase infusion in patients with acute pulmonary embolism (PE). Since then, the management of arterial thrombosis, with coronary artery thrombosis in particular, has advanced dramatically, with incredible advances in diagnosis, risk assessment, methods of treatment, and posttreatment care. The interventional treatment of PE, in contrast, has moved little.

CURRENT STATE OF PE THERAPY
Despite the lack of dramatic change in interventional therapies, the care of patients with PE has matured during this time. These changes have come primarily in diagnosis and noninvasive therapeutics. The obvious examples include rapidly acquired computed tomographic angiographic assessment of the pulmonary arteries, supplanting the vague and difficult-to-interpret ventilation-perfusion nuclear scan, and the improvements in anticoagulants.

The current use of more-selective, injectable, low-molecular- weight heparins and specific antifactor Xa agents and—soon, hopefully—oral factor Xa inhibitors and direct thrombin inhibitors suggest a bright future for the subacute and chronic management of these patients. Targeting of therapy has also come to pass, with randomized clinical trials showing the benefit of chronic administration of lowmolecular- weight heparin instead of warfarin in patients with cancer-related venous thromboembolism.

However, what is the state of interventional therapies in PE? Has it progressed akin to coronary interventions? In coronary interventions, with the comfort and support of large, randomized clinical trials, practitioners know the best methods of arterial revascularization, adjunctive agents, timing of intervention, biomarkers to determine which patient subsets are most likely to benefit, and methods of follow-up. Can the same claims be made for PE? At best, small studies have demonstrated the feasibility of clinical trials in this arena. It is now time for peripheral interventionists to conceive, conduct, and advance clinical trials in PE to determine its best treatment.

WHERE DO WE BEGIN?
For interventionists, I would submit that two areas need randomized clinical trials to begin as quickly as possible. First, despite decent evidence suggesting that patients with elevations in biomarkers such as troponin I or T or brain natriuretic peptide, increases in right ventricular size by computed tomography, or impairments in right ventricular function by echocardiogram confer a worse prognosis in PE, no study has demonstrated that treating patients based on these prognostic markers makes a difference. As members of the vascular community of physicians, we need to figure out who can be treated effectively with medications alone and who requires more urgent thrombolytic care. Second, the best method of thrombolysis remains unknown. Parenteral administration permits wide use of the therapy among a variety of clinicians and clinical settings, yet it seems obvious that lower-dose, directed therapy applied through locally placed catheters would lead to better thrombolysis with a lower bleeding risk. How have 4 decades passed without the comparison of these two methods of thrombolytic therapy being tested?

It is estimated that approximately 700,000 people in the United States develop PE each year. Currently, the mortality rate after PE is approximately 10% for all-comers and more than 20% in the presence of a positive biomarker. Moreover, 4% of survivors will develop chronic dyspnea as a result of chronic thromboembolic pulmonary hypertension. The high event rates in a very large patient population provide a ready opportunity for the interventional community to render important advances with modest effort. We should take up the mantle.

This article was previously published in the VIVA Today coverage of the 2009 Vascular Interventional Advances meeting.

Joshua A. Beckman, MD, MS, is Assistant Professor of Medicine, Cardiovascular Fellowship, at Brigham and Women's Hospital in Boston, Massachusetts. He has disclosed that he has received honoraria for talks from GlaxoSmithKline. Dr. Beckman may be reached at jbeckman@partners.org.