Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism.
BACKGROUND
The clinical benefit of thrombolytic treatment over heparin in patients with pulmonary embolism without hemodynamic compromise remains controversial. In these patients bolus tenecteplase has the potential to provide an effective and safe thrombolysis.


METHODS
We evaluated the effect of tenecteplase on right ventricle dysfunction (RVD) assessed by echocardiography in hemodynamically stable patients with PE in a multicenter, randomized, double-blind, placebo-controlled study. RVD was defined as right/left ventricle end-diastolic dimension ratio >1 in the apical 4-chamber view. Patients were randomized to receive weight-adjusted single-bolus tenecteplase or placebo. All patients received unfractionated heparin. Reduction of RVD at 24 hours was the primary efficacy end-point and was evaluated by an independent committee unaware of treatment allocation.


RESULTS
Overall, 58 patients were randomized. Echocardiograms were adequate for efficacy analysis in 51 patients, 23 randomized to tenecteplase and 28 to placebo. The reduction of right to left ventricle end-diastolic dimension ratio at 24 hours was 0.31+/-0.08 in patients randomized to tenecteplase as compared to 0.10+/-0.07 in patients randomized to placebo (p=0.04). One patient randomized to tenecteplase suffered a clinical event (recurrent pulmonary embolism) in comparison to three patients randomized to placebo (1 recurrent pulmonary embolism; 1 clinical deterioration and 1 non pulmonary embolism-related death). Two non fatal major bleedings occurred with tenecteplase (1 intracranial) and one with placebo.


CONCLUSIONS
In hemodynamically stable patients with PE, treatment with single bolus tenecteplase is feasible at the same dosages used for acute myocardial infarction and is associated with reduction of RVD at 24 hours. Whether this benefit is associated with an improved clinical outcome without excessive bleeding is currently explored in a large clinical trial.
Becattini
Cecilia
C
Medicina Interna e Cardiovascolare-Stroke Unit, Università di Perugia, Perugia, Italy. cecilia.becattini@unipg.it
Agnelli
Giancarlo
G
Salvi
Aldo
A
Grifoni
Stefano
S
Pancaldi
Leonardo Goffredo
LG
Enea
Iolanda
I
Balsemin
Franco
F
Campanini
Mauro
M
Ghirarduzzi
Angelo
A
Casazza
Franco
F
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D004304:Dosage Forms; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005240:Feasibility Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006470:Hemorrhage / Q000150:complications; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011655:Pulmonary Embolism / Q000150:complications* / Q000000981:diagnostic imaging; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging / Q000188:drug therapy*
D000925:Anticoagulants; D004304:Dosage Forms; D005343:Fibrinolytic Agents; D006493:Heparin; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase