title: Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.
abstract: BACKGROUND
  The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism remains controversial.
  
  
  METHODS
  We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dysfunction but without arterial hypotension or shock. The patients were randomly assigned in double-blind fashion to receive heparin plus 100 mg of alteplase or heparin plus placebo over a period of two hours. The primary end point was in-hospital death or clinical deterioration requiring an escalation of treatment, which was defined as catecholamine infusion, secondary thrombolysis, endotracheal intubation, cardiopulmonary resuscitation, or emergency surgical embolectomy or thrombus fragmentation by catheter.
  
  
  RESULTS
  Of 256 patients enrolled, 118 were randomly assigned to receive heparin plus alteplase and 138 to receive heparin plus placebo. The incidence of the primary end point was significantly higher in the heparin-plus-placebo group than in the heparin-plus-alteplase group (P=0.006), and the probability of 30-day event-free survival (according to Kaplan-Meier analysis) was higher in the heparin-plus-alteplase group (P=0.005). This difference was due to the higher incidence of treatment escalation in the heparin-plus-placebo group (24.6 percent vs. 10.2 percent, P=0.004), since mortality was low in both groups (3.4 percent in the heparin-plus-alteplase group and 2.2 percent in the heparin-plus-placebo group, P=0.71). Treatment with heparin plus placebo was associated with almost three times the risk of death or treatment escalation that was associated with heparin plus alteplase (P=0.006). No fatal bleeding or cerebral bleeding occurred in patients receiving heparin plus alteplase.
  
  
  CONCLUSIONS
  When given in conjunction with heparin, alteplase can improve the clinical course of stable patients who have acute submassive pulmonary embolism and can prevent clinical deterioration requiring the escalation of treatment during the hospital stay.
authors.affiliation: Department of Cardiology and Pulmonary Medicine, Georg-August-Universität, Göttingen, Germany. skonstan@med.uni-goettingen.de
authors.forename: Stavros
authors.initials: S
authors.lastname: Konstantinides
authors.forename: Annette
authors.initials: A
authors.lastname: Geibel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heusel
authors.forename: Fritz
authors.initials: F
authors.lastname: Heinrich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kasper
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014463:Ultrasonography; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging / Q000209:etiology
chemical_list: D005343:Fibrinolytic Agents; D006493:Heparin; D010959:Tissue Plasminogen Activator