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

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Abstract

Background 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. Methods 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. Results 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. Conclusions 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. (Am Heart J 1999;138:39-44.)

Section snippets

Methods

The study protocol was approved by Göttingen University’s Ethical Review Committee and was conducted in 9 centers throughout Germany.

Patient characteristics

Thirty-six patients were enrolled between May 1994 and October 1996. Twenty-three patients were treated with reteplase and 13 patients received alteplase. The patients of the 2 groups were well matched for baseline characteristics. As displayed in Table I there were no significant differences between the 2 groups with respect to age, height, sex, onset of symptoms, stage of pulmonary embolism, clinical symptoms, or baseline hemodynamic characteristics.

. Baseline characteristics (means and

Discussion

The primary objective of the study was to compare the effects of double bolus reteplase with the standard regimen of alteplase in patients with acute pulmonary embolism. The study was specifically designed to evaluate early hemodynamic changes during the first few hours after administration of the thrombolytic. High total pulmonary resistance, high pulmonary artery pressure, and low cardiac index are immediately life-threatening in the most severely affected patients. The mean pulmonary artery

Acknowledgements

We thank Egon Pfarr, MSc, and Adalbert Smolartz, MD, for their extremely valuable contributions.

References (22)

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Supported by research grants from Boehringer Mannheim Therapeutics, Mannheim, Germany.

☆☆

Reprint requests: Ulrich Tebbe, MD, Medizinische Klinik Lippe-Detmold, Röntgenstraße 18, 32756 Detmold, Germany.

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