Prof. Steen Dalby Kristensen ,
Fibrinolytic therapy improves short term outcome without causing excessive bleeding in patients with submassive pulmonary embolism.
Fibrinolytic therapy is recommended in patients with massive pulmonary embolism and haemodynamic instability/shock. The use of fibrinolytic therapy in patients with submassive pulmonary embolism is more debatable.
The effect of alteplase in this setting was evaluated in a German double-blinded multicenter study (1). The patients had pulmonary embolism verified by lung scintigraphy, spiral CT-scan or pulmonary angiography and pulmonary hypertension, right ventricular dysfunction or both (verified by echocardiography or right sided heart catheterization) and onset of symptoms within 96 hours. Of 256 patients enrolled, 118 were randomised to heparin plus 100 mg of alteplase (infused over 2 hours) and 138 patients were randomised to heparin plus placebo. The primary endpoint was the occurrence of death or clinical deterioration requiring an escalation in treatment defined as catecholamine infusion, secondary thrombolysis, endotracheal intubation , cardiopulmonary resuscitation, emergency surgical embolectomy or fragmentation of emboli by the use of a catheter evaluated at time of discharge or after 30 days.
The incidence of the primary endpoint was significantly higher in the heparin-plus-placebo group than in the heparin-plus-alteplase group (p=0.006) and the probability of event free survival was higher in the heparin-plus-alteplase group (p=0.005). This difference was due to the higher incidence of treatment escalation in the heparin-plus-placebo group (24.6% vs 10.2%, p=0.004). Mortality was low in both groups (3.4% vs 2.2%, p=0.71). The incidence of bleeding was also low, and no fatal or cerebral bleeding occurred in the patients receiving heparin-plus-alteplase.
This study shows for the first time that fibrinolytic therapy with alteplase improves short term outcome in patients with submassive pulmonary embolism without causing an excess of bleeding episodes. In the study pulmonary embolism was diagnosed by either lung-scintigraphy, spiral-CT scan or angiography. Patients older than 80 years were excluded as were patients with an increased risk of bleeding. Mortality rate was low and conduction of a mortality trial on this patient group seem to be unrealistic.
Long term data from the trial may elucidate the effect of fibrinolytic therapy on the incidence of secondary pulmonary hypertension. However, the study strongly supports the use of fibrinolytic therapy in patients with submassive pulmonary embolism.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
1. Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002; 347: 1143-50.
Steen Dalby Kristensen, MD, DMSc Vice-chairman ESC WG on Thrombosis Head of Cardiology Skejby Hospital Aarhus University Hospital DK-8200 Aarhus N Denmark email@example.com
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