Study Design Summary: Prospective, single center, unblinded study of 121 patients with a predefined “moderate” pulmonary embolism were given either half dose tPA with anticoagulation or only anticoagulation. Primary outcome was pulmonary hypertension at 28 months and a composite of pulmonary hypertension and recurrent PE at 28 months.
Notes: The study predefined a “moderate” PE and in an unblinded fashion randomized patients to either half dose tPA with anticoagulation or only anticoagulation. Anticoagulation choice was either UFH or LMWH with preference for LMWH. 79% of patients in the tPA group and 81% in the AC only group received LMWH as opposed to UFH. Pulmonary embolism was imaging confirmed. The dosing for tPA was 0.5mg/kg up to 50mg with 10% as bolus over 1 minute followed by the remaining 90% over 2 hours.
The groups were equal in their baseline characteristics such as age, past medical history, history of previous unprovoked PE/VTE, hormone therapy, smoking history. The intervention vs control group had a mean pulmonary artery systolic pressure of 50 vs 51 mm Hg on admission, this quickly diverged after treatment with final numbers at 28 months of 28 vs 43 mm Hg (p<0.001). In the intervention vs control group there was 9 vs 32 patients with pulmonary hypertension at 28 months (p<0.001) and 9 vs 35 with composite of pulmonary hypertension and recurrent PE at 28 months (p<0.001). The secondary outcomes of mortality, hospital stay in days and recurrent PE all favored the tPA group. There was no bleeding in either group which does raise question, especially considering this wasn’t a blinded study.
Since the study was unblinded, only moderately sized and with unique definitions of size of PE rather than conventional massive/submassive/non-massive the results are hard to extrapolate to current practice but they do show decent results that even patients without massive PE can benefit from tPA and that half dose tPA may be safe. The authors offer up the explanation that since the lungs are the only organ to receive 100% of the cardiac output that half dose tPA is effective and can reduce bleeding complications-which the results of their study also seem to support. Although the study was unblinded to the patients and the treating clinicians, the cardiologists reading the ECHOs were blinded.
Due to the composite outcome we cannot definitely stay if it reduces recurrent PE. The study does not direct address mortality as a primary outcome thus no conclusion can be drawn about this outcome either.
Study Conclusion: “Safe” dose tPA is safe and effective in reducing pulmonary hypertension and recurrent PE at 28 months for patients with “moderate” PE.
Fusion Beat Bottom Line Impression: Half dose tPA reduces rates of pulmonary hypertension at 28 months and does not increase risk of bleeding compared to anticoagulation alone.
A Fusion Beat 