Elsevier

Thrombosis Research

Volume 125, Issue 3, March 2010, Pages e82-e86
Thrombosis Research

Regular Article
Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism

https://doi.org/10.1016/j.thromres.2009.09.017Get rights and content

Abstract

Introduction

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.

Conclusion

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.

Introduction

In patients with acute pulmonary embolism (PE), right ventricle dysfunction (RVD) assessed by echocardiography is associated with an adverse in-hospital outcome. In patients with PE and RVD, in-hospital mortality ranges from 5 to 17% [1], [2], [3], [4]. RVD maintains its prognostic value in hemodynamically stable patients with PE. Indeed, in these patients RVD is associated with an in-hospital mortality of about 5%, significantly higher than in patients without RVD [3], [4]. Thrombolytic treatment is currently recommended for patients with PE who present with shock or sustained hypotension [5], [6]. The clinical benefit of thrombolytic treatment in hemodynamically stable patients with PE and RVD remains to be defined [7].

Tenecteplase, a thrombolytic agent derived from tissue-type plasminogen activator (tPA) [8], is currently used for treatment of patients with myocardial infarction [9], [10]. Tenecteplase has a relatively long half life and this allows its bolus administration. Case series on tenecteplase administration in patients with acute PE have been recently published [11], [12], [13].

We performed a randomized, double-blind, multicenter, placebo controlled study aimed at assessing the effect of tenecteplase on RVD in hemodynamically stable patients with PE. All patients received anticoagulant treatment with unfractionated heparin.

Section snippets

Study patients

Consecutive patients, aged between 18 and 85 years, with an objective diagnosis of PE were considered for inclusion in the study if they had: 1) onset of symptoms since no more than 10 days, 2) normal blood pressure (systolic blood pressure  100 mmHg), and 3) RVD at echocardiography performed within 24 hours from the diagnosis of PE. Patients were asked to provide a written informed consent before randomization.

The diagnosis of PE was to be done by multidetector CT-scan, pulmonary angiography, or

Results

Overall, 58 patients were included in the study, 28 assigned to tenecteplase and 30 to placebo. Overall, the more common exclusion criteria were impossibility to record baseline echocardiography, recent surgery and cancer at increased risk for bleeding.

Patients’ features according to treatment allocation are shown in Table 1. Patients assigned to tenecteplase were older than patients assigned to placebo (mean age ± SE 72.1 ± 1.2 and 64.5 ± 2.5, respectively p = 0.01). Heart rate at randomization was

Discussion

This is the first randomized study with tenecteplase in patients with acute PE. Overall, the study shows the feasibility of tenecteplase treatment in patients with acute PE and does not raise safety concerns. Moreover, this study suggests that tenecteplase can be used in patients with acute pulmonary embolism at the same doses used in patients with myocardial infarction. Indeed, in the absence of specific data, the dose schedule for tenecteplase was retained from studies in patients with acute

Conflict of interest statement

None.

Acknowledgements

This work has been supported by a grant in aid from Boehringer Ingelheim, Italy to the Clinical Research Unit of the University of Perugia.

References (21)

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1

Other authors were: Pietro Berra Centurini, MD, Poliambulanza, Brescia; Francesco Bovenzi, MD, Presidio Ospedaliero Piana di Lucca, Lucca; Daniele Coen, MD, Azienda Ospedaliera Ospedale Niguarda ‘Cà Granda’, Milano; Antonio Palla, MD, Ospedale Cisanello, Università di Pisa; Fernando Porro, MD, IRCCS Ospedale Maggiore di Milano; Jorge Antonio Salerno Uriarte, MD, Ospedale di Circolo e Fondazione Macchi, Varese.

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