Regular ArticleBolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism☆
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)
- et al.
Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry
Lancet
(1999) - et al.
Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Chest
(2008) - et al.
Tenecteplase for massive pulmonary embolus
Resuscitation
(2002) - et al.
Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion
Lancet
(1993) - et al.
Acute pulmonary embolism treated with tissue plasminogen activator
Lancet
(1986) - et al.
PAIMS 2: Alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen Activator Italian Multicenter Study 2
JACC
(1992) - et al.
Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism
Heart
(1997) - et al.
Short term clinical outcome of patients with pulmonary embolism, normal blood pressare and echocardiographycal right ventricular dysfunction
Circulation
(2000) - et al.
Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher
Arch Intern Med
(2005) - et al.
Guidelines on the diagnosis and management of acute pulmonary embolism: the task force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology
Eur Heart J
(2008)
Cited by (159)
Safety and efficacy of clot-dissolving therapies for submassive pulmonary embolism: A network meta-analysis of randomized controlled trials
2024, Cardiovascular Revascularization MedicineContemporary practice patterns and outcomes of systemic thrombolysis in acute pulmonary embolism
2022, Journal of Vascular Surgery: Venous and Lymphatic DisordersAntithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report
2021, ChestCitation Excerpt :The panel dyad reviewed 423 abstracts, from which they selected 29 full texts for review. Studies selected for abstraction and synthesis are detailed in Table 5.68–85,86 The panelists determined that the desirable effects of the intervention are small in magnitude, whereas the undesirable effects are moderate.
- ☆
Clinical Trial Registration Information: NCT00222651.
- 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.