PAIMS-2 - ALTEPLASE COMBINED WITH HEPARIN VERSUS HEPARIN IN THE TREATMENT OF ACUTE PULMONARY-EMBOLISM - PLASMINOGEN-ACTIVATOR ITALIAN MULTICENTER STUDY-2

Background. The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms. Objectives. The aim of this randomized, open trial was to evaluate the efficacy and safety of alteplase followed by heparin, versus heparin alone, in 36 patients with angiographically documented pulmonary embolism. Methods. Twenty patients were allocated randomly to a 2-h infusion of alteplase (10 mg bolus, then 90 mg over 2 h) followed by heparin; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h. Results. The vascular obstruction, assessed by the Miller index at pulmonary angiography, decreased significantly in alteplase-treated patients (p < 0.01) from a baseline of 28.3 +/- 2.9 to a value of 24.8 +/- 5.2 2 h after the start of infusion; in the heparin group there was no change (from 25.3 +/- 5.3 to 25.2 +/- 5.4). Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 +/- 7.8 mm Hg to 21.4 +/- 6.7 in the alteplase group and increased in the heparin group (from 22.3 +/- 10.5 to 24.8 +/-11.2 mm Hg). For a subset of patients, lung scans were performed at baseline and on days 7 and 30. There were no differences between the two groups in the follow-up lung scans, but there were significant decreases from the baseline values. Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group (p = NS). There were three major bleeding episodes in the alteplase group and two in the heparin group. Two patients died after fibrinolysis (one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage) and one patient in the heparin group died of recurrent pulmonary embolism. Conclusions. Alteplase resulted in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin. However, the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given.