Impact of Thrombolytic Therapy on Pulmonary Embolism

Study Questions:

What is the long-term prognosis of patients with intermediate-risk pulmonary embolism (PE), and what are the effects of thrombolytic therapy on the persistence of symptoms or the development of late complications?

Methods:

The authors explored long-term complications among patients enrolled in the PEITHO (Pulmonary Embolism Thrombolysis) trial, a randomized (1:1) comparison of thrombolysis with tenecteplase vs. placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction, and a positive cardiac troponin test. Of the original 1,006 patients in the PEITHO trial, 709 were included at sites participating in the long-term follow-up protocol.

Results:

Over a median of 37.8 months, mortality rates were 20.3% in the thrombolysis arm and 18.0% (p = 0.43) in the placebo arm. At follow-up examination, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% vs. 30.1% of patients (p = 0.23). Echocardiography (performed in 144 and 146 patients in the thrombolysis and placebo arms, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 2.1% and 3.2% of cases, respectively (p = 0.79).

Conclusions:

The authors concluded that approximately 33% of patients with intermediate-high risk PE report some degree of persistent functional limitation, but rarely develop CTEPH. The authors also concluded that the use of thrombolytic therapy did not affect long-term mortality, dyspnea, or RV dysfunction.

Perspective:

This long-term (~3-year) follow-up of the PEITHO trial failed to show benefit associated with the use of systemic thrombolytic therapy for patients with intermediate-high risk (submassive) PE. While conceptually the use of thrombolytic therapy was hypothesized to reduce early mortality and long-term morbidity associated with intermediate-high risk PE, both the short-term (N Engl J Med 2014;370:1402-11) and this long-term follow-up analysis failed to show mortality benefit. While the short-term analysis demonstrated a 3.0% absolute risk reduction in death or hemodynamic compromise, the long-term outcomes of persistent dyspnea, RV dysfunction, or CTEPH did not differ between the two groups. Whether more advanced therapies, such as catheter-directed thrombolysis, would offer similar benefit with less risk that translates to favorable long-term benefits remains to be tested. In the meantime, most patients with hemodynamically stable acute PE can be treated safely with anticoagulation therapy, close monitoring, and rescue reperfusion at the earliest signs of hemodynamic decompensation.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Lipid Metabolism, Pulmonary Hypertension, Echocardiography/Ultrasound

Keywords: Anticoagulants, Dyspnea, Echocardiography, Fibrinolytic Agents, Hemodynamics, Hypertension, Pulmonary, Pulmonary Embolism, Secondary Prevention, Thrombolytic Therapy, Tissue Plasminogen Activator, Ventricular Dysfunction, Right, Vascular Diseases


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