• Cardiology Clinical Trials
• Thrombotic Disorders
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• Thromboembolic Disease

Pulmonary embolism (PE) is one of the most common preventable causes of death (responsible for >100,000 deaths annually) and the third leading cause of cardiovascular mortality. Thrombolysis with standard doses of 100 mg tissue plasminogen activator (t–PA) over 2 hours is recommended in appropriately selected severe PE patients (patients with hemodynamic instability and shock), but these patients only represent 5% of all presentations with PE. Patients with moderate PE constitute a more prevalent population; however, there are often concerns about major bleeding (which occurs in 6% to 20% of cases) and intracranial hemorrhage (ICH; 2% to 6% of cases) in moderate PE patients when larger doses of t–PA are employed. In addition, practitioners are hesitant to use t–PA when patients are hemodynamically stable and/or receiving concomitant parenteral anticoagulation due to concern that the risks outweigh the benefits. PE is exquisitely sensitive to thrombolysis, as the lungs are the point of convergence of venous circulation; so, a majority of IV–delivered t–PA converges to the clot, making t–PA ideal for the treatment of this population of patients.

New data from the Moderate Pulmonary Embolism Treated with Thrombolysis (MOPETT) study, presented by Mohsen Sharifi, MD, A.T. Still University, Mesa, Arizona, USA, suggest that moderate PE patients may be managed with reduced–dose t–PA and modified anticoagulation.

MOPETT was a randomized trial of 121 patients (45% men; mean age 59 years). Sixty–one patients received t–PA that was dose–adjusted for weight (for those ≥50 kg, an initial dose of 10 mg t–PA over 1 minute, followed by a 40–mg infusion over 2 hours; for those <50 kg, a total t–PA dose of 0.5 mg/kg, delivered as an initial dose of 10 mg over 1 minute, followed by the remainder as an infusion over 2 hours) in addition to a 20% to 30% reduction in anticoagulant dose (either enoxaparin or heparin), and 60 subjects received anticoagulation alone (standard of care). The coprimary endpoints were pulmonary hypertension (PH) and a composite of PH plus recurrent PE after 28 months of follow–up. The determination of PH was by echocardiography, defined as an estimated pulmonary artery systolic pressure (PASP) >40 mm Hg. Secondary endpoints included in–hospital bleeding, duration of hospitalization, and mortality. Patients were included in this study if they had symptomatic PE plus 2 of the following risk factors for post–PE mortality: chest pain, tachypnea >22 respirations per minute, tachycardia resting heart rate >90 beats per minute, dyspnea, jugular venous pressure >12 cm H₂0, cough, or oxygen desaturation <90%.

Serial changes in PASP from baseline to 28 months by treatment strategy are shown in Table 1. After 28 months, 16% of t–PA patients experienced PH (the first coprimary endpoint) compared with 57% of those who were assigned standard anticoagulation (p<0.001). Patients who were treated with t–PA also had significantly fewer incidences of the second coprimary endpoint, a composite of PH plus recurrent PE at 28 months (16% vs 63%; p<0.001). Secondary events occurred infrequently, in particular mortality, and are shown according to treatment assignment in Table 2. No significant in–hospital bleeding occurred with either strategy.

The authors concluded that the use of low–dose thrombolysis appeared to be safe and effective in moderate PE to reduce PH, recurrent PE, and hospital stay without an increase in bleeding risk or ICH. However, hard clinical events, such as mortality, clinically evident right–heart failure, and major bleeding events, were infrequent. Larger and long–term studies that test this strategy in representative patients are necessary to ultimately determine whether modified aggressive reperfusion therapy provides more benefit than harm in PE.

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