Hemodynamic effects of double bolus reteplase versus alteplase infusion in massive pulmonary embolism

Thrombolytic agents are given in massive pulmonary embolism to dissolve or reduce the clot and normalize hemodynamics. Comparative clinical studies have shown that administration of a 2-hour infusion of alteplase is more effective than urokinase over a 12-hour period. Reteplase is a new generation thrombolytic with a longer half-life that can be administered more conveniently as a double bolus. We compared efficacy and safety of reteplase with the approved regimen of alteplase in massive pulmonary embolism.

Thirty-six patients were enrolled and randomly assigned: 23 received reteplase and 13 received alteplase along with intravenous heparin. Reteplase was administered as 2 intravenous bolus injections of 10 U 30 minutes apart, and alteplase was administered as an intravenous infusion of a total dose of 100 mg over a 2-hour period, including an initial 10-mg bolus. Diagnosis of pulmonary embolism was confirmed by selective pulmonary angiography. Hemodynamic monitoring was conducted during the first 24 hours after administration. The primary end point was change in total pulmonary resistance. Secondary variables were pulmonary pressure, cardiac index, clinical parameters, and adverse events.

The primary parameter of total pulmonary resistance showed a significant decrease after just 0.5 hours in the reteplase group and after 2 hours in the alteplase group, with a further decrease persisting for up to 24 hours in both treatment groups. A similar pattern was seen in other directly measured hemodynamic parameters, especially mean pulmonary artery pressure and cardiac index; there was no significant difference between reteplase and alteplase. There was also no apparent difference between the treatment groups with respect to safety, and no stroke or intracranial hemorrhage occurred. The rate of bleedings and the incidence of nonhemorrhagic adverse events were as expected for patients with pulmonary embolism treated with a thrombolytic agent.

Reteplase is suitable for treatment of massive pulmonary embolism with a standard double bolus 10 + 10 U. Efficacy of reteplase appeared to be at least as good at decreasing pulmonary vascular resistance as that of the approved alteplase regimen of 100 mg infusion over a 2-hour period.