Alteplase for Submassive PE

August 19, 2017

On the Shoulders of Giants

Spoon Feed
This early study of thrombolytics plus heparin for submassive PE showed no mortality benefit but did show a decrease in need for escalation of care compared with heparin alone.  Subsequent studies cast doubt on lytics for submassive PE, so take the latest evidence into account as you read this older study.

Why does this matter?
Routine anticoagulation is all that is needed for PE that does not cause RV dysfunction or injury.  Thrombolytic therapy is clearly indicated for hemodynamically unstable, so called, massive PE.  But the in between group, submassive PE, is less clear.  Lytics are not without bleeding risk.  But a big PE isn’t risk-free either.  This was an early study to sort this out.  See below for the latest evidence on treatment of submassive PE.

Is it a blood clog, doc?
This was an early industry-funded double-blinded RCT of about 250 patients with submassive PE (RV dysfunction on echo, pulmonary hypertension on Swan-Ganz catheter, or new ECG changes of RV strain) who received heparin vs heparin plus alteplase.  For the composite outcome of need for escalation of therapy or in-hospital mortality, the lytic group did better.  The improvement was not due to mortality benefit but solely to reduced risk for escalation of treatment: 10.2% vs 24.6%, lytic + heparin vs heparin group, respectively.  The majority of this benefit was reduction of secondary thrombosis in the lytic group.  Since then, in 2014, PEITHO found lytics reduced risk of hemodynamic decompensation in “intermediate-risk PE” but at the cost of increasing the risk of major hemorrhage and stroke.  And a long-term follow up of PEITHO in 2017 showed no reduction in mortality, dyspnea, or chronic pulmonary hypertension in the thrombolytic group at 3-year follow up.

Source
Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.  N Engl J Med. 2002 Oct 10;347(15):1143-50.

Another Spoonful
Life in the Fast Lane has a comprehensive, fantastic review of lytics for submassive PE.