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Pulmonary embolism (PE) is an acute, life-threatening condition with mortality rates as high as 35% if left untreated.1 In severe cases, acute PE can be further classified as massive or submassive. Massive PE is defined as an acute PE with any of the following: persistent hypotension, persistent severe bradycardia or pulselessness.2 Massive PE is treated with full-dose tissue plasminogen activator (tPA 10 mg bolus, followed by 90 mg over 2 hours) followed by full dose anticoagulation.3 Submassive PE is defined as an acute PE without systemic hypotension but with right-sided heartstrain, myocardial necrosis or pulmonary arterial hypertension (PAH). For submassive PE treatment, the use of tPA is more controversial. In 2002, Konstantinides et al. evaluated the use of heparin plus full-dose tPA compared to heparin alone in patients with submassive PE and found that the combination prevented the composite primary end-point of escalation of treatment or in-hospital death (P=0.006), though mortality was low in both groups (2.2% and 3.4%).4 Despite these results, clinicians have been reluctant to use thrombolysis in submassive PE due to the risk of intracerebral hemorrhage, which occurs in 0.7% to 6.4% of all tPA patients.5,6 In contrast to other organs, the lungs are the only organ to receive the entire cardiac output which makes the lungs distinctly sensitive to thrombolysis and may not require full-dose tPA such, the MOPETT (Moderate Pulmonary Embolism Treated with Thrombolysis Trial), a prospective, single-center, randomized controlled trial, assessed the safety and efficacy of low-dose thrombolysis (tPA 10 mg bolus, followed by 40 mg over 2 hours if >50 kg) plus anticoagulation compared to anticoagulation alone in moderate PE.7

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The MOPETT trial included patients with a “moderate” PE defined as two or more signs and symptoms suggestive of a PE and a positive diagnostic test (computed tomography angiography or ventilation/perfusion scan) suggestive of ≥2 lobe involvement. Patients were excluded if they had symptom onset of >10 days, eligible for full-dose thrombolysis (massive PE), > 8 hours since parenteral anticoagulation was initiated, systolic blood pressure of < 95 mm Hg or ≥ 200/100 mm Hg, severe thrombocytopenia (platelets < 50,000) or a contraindication to anticoagulation. The primary outcome was the development of pulmonary arterial hypertension (PAH, defined as pulmonary artery systolic pressure ≥ 40 mm Hg) and the composite of PAH plus recurrent PE. The secondary outcomes were mortality, recurrent PE, length of hospital stay and bleeding.7

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A total of 121 patients were randomized to either the thrombolysis group (n=61) or the control group (n=60) with a mean follow-up time of 28 months. Baseline characteristics were similar between the groups with 20% of both groups having previous venous thromboemboli. Both groups received anticoagulation consisting of either UFH or subcutaneous enoxaparin, with a preference given to enoxaparin. The thrombolysis group received anticoagulation during the tPA infusion time, though at adjusted rates, and warfarin was initiated in all patients on admission. The combination of thrombolysis and anticoagulation compared to anticoagulation alone was shown to be more efficacious in reducing PAH (16% vs. 57%, P<0.001) and the composite of PAH and recurrent PE (16% vs. 63%, P<0.001). Hospital stay duration was shorter in the thrombolysis group (2.2 ± 0.5 vs. 4.9 ± 0.8 days, respectively, P<0.001). No significant differences were found with total mortality, recurrent PE or the composite of total mortality and recurrent PE. No bleeding events occurred in either study groups, though bleeding criteria were never defined.7

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Sharifi and colleagues showed that low-dose tPA for the treatment of “moderate” PE is efficacious and safe, resulting in a significant reduction in PAH after 28±5 months. Based on these results, low-dose tPA in combination with anticoagulation may be a viable treatment option ...

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