Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double‐blind, placebo‐controlled randomized trial

Abstract

of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebocontrolled randomized trial. J Thromb Haemost 2014; 12: 459-68.Summary. Background: Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance. Objective: Test if tenecteplase increases the probability of a favorable composite patient-oriented outcome after submassive PE. Methods: Normotensive patients with PE and right ventricular (RV) strain (by echocardiography or biomarkers) were enrolled from eight hospitals. All patients received lowmolecular-weight heparin followed by random assignment to either a single weight-based bolus of tenecteplase or placebo, administered in a double-blinded fashion. The primary composite outcome included: (i) death, circulatory shock, intubation or major bleeding within 5 days or (ii) recurrent PE, poor functional capacity (RV dysfunction with either dyspnea at rest or exercise intolerance) or an SF36â Physical Component Summary (PCS) score < 30 at 90-day follow-up. Results: Eighty-three patients were randomized; 40 to tenecteplase and 43 to placebo. The trial was terminated prematurely. Within 5 days, adverse outcomes occurred in three placebo-treated patients (death in one and intubation in two) and one tenecteplase-treated patient (fatal intracranial hemorrhage). At 90 days, adverse outcomes occurred in 13 unique placebo-treated patients and five unique tenecteplase-treated patients Thus, 16 (37%) placebo-treated and six (15%) tenecteplase-treated patients had at least one adverse outcome (exact two-sided P = 0.017). Conclusions: Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome.

Impact of tenecteplase in intermediate and high risk pulmonary embolism

“…In Topcoat and Peitho trial in hospital mortality was 2.6% and 2.5% in IR group cases as compared to our study in which it was 3.2%. 26,27 Although there are only 3 single centric trials of which this study is the latest showing almost similar mortality rates as compared to previous trials in IR group. While the HR group was never compared alone in various other studies but the benefits of thrombolytic agents was shown in our study in 89% HR cases (Table 5).…”

The role of thrombolytic therapy in pulmonary embolism

“…42 All studies were randomized, but only 7 were clearly blinded. 10,15,16,20,21,24,25 Allocation concealment and sequence generation were unclear in 3 studies. 13,14,17 Here, we summarize our results in correspondence with several key questions we identified.…”

“…There were 16 studies that compared thrombolysis to anticoagulation, and included a total of 2087 patients (Table 1). [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] An additional 16 studies compared different types of thrombolytic agents, and included a total of 1244 patients (supplemental Appendix 5). [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] One study (Ultrasound-Accelerated Thrombolysis of Pulmonary Embolism [ULTIMA] trial) investigated catheter-directed thrombolysis (CDT), and enrolled a total of 59 patients.…”

Terapia trombolítica en TEP submasivo/riesgo intermedio: Evidencias y sugerencias post estudio Pulmonary Embolism Thrombolysis (PEITHO)

“…Algunas 48 intentó demostrar la utilidad de agregar tenecteplase en TEP submasivo. Además de buscar bajar mortalidad, intubación o shock, se diseñó un outcome compuesto a 3 meses del evento para evaluar morbilidad, considerando: nuevo TEP, funcionalidad cardiovascular y percepción de salud.…”

“…A pesar de ser multicéntrico sólo reclutó 84 pacientes en 4 años; no demostraron diferencias en eventos adversos precoces (2,5% vs 6,9%) tampoco los aspectos de la evaluación funcional a 3 meses, salvo una percepción general de salud que favorece el grupo que utilizó tenecteplase (3,3 vs 2,4, p = 0,036) 48 . El principal aporte del estudio TOPCOAT fue introducir la importancia de medir morbilidad a largo plazo como outcome clínico relevante.…”