The severity classification of an acute pulmonary embolism dictates the appropriate course of initial therapy. According to the American College of Chest Physician Guidelines, thrombolytic therapy should be reserved for patients who present with hypotension without a high bleed risk.1 Right ventricular dysfunction, as well as positive cardiac troponin I or troponin T tests are both prognostic qualities of an acute pulmonary embolism and predictors of increased mortality. Patients exhibiting these signs without experiencing hemodynamic instability are considered to be intermediate risk.2 The PEITHO (Pulmonary EmbolIsm THrOmbolysis) trial sought to determine the efficacy of thrombolytic therapy, specifically tenecteplase, in intermediate-risk pulmonary embolism patients presenting with right ventricular dysfunction, and myocardial injury.2
The PEITHO trial was a prospective, multicenter, international, double-blind, placebo-controlled randomized trial evaluating the use of a weight-based single bolus tenecteplase injection, in normotensive patients with an acute pulmonary embolism and an intermediate risk of an adverse outcome.2 Patients were assigned to one of two treatment arms: tenecteplase (30mg-50mg) with heparin (UFH or LMWH) or placebo with heparin. The primary efficacy outcome was death from any cause, or hemodynamic decompensation within 7 days after randomization. The primary safety outcomes were ischemic or hemorrhagic stroke and extracranial major bleeding within 7 days after randomization, as well as any serious adverse event within 30 days.2 Rescue thrombolysis was given to any patient whose clinical condition was deteriorating based on worsening of symptoms, worsening respiratory failure, arterial hypotension or shock, persistent or worsening pulmonary hypertension or right ventricular dysfunction.3 A major bleeding event was considered to be moderate if the bleeding episode required blood transfusions but not deemed life-threatening or did not lead to hemodynamic compromise requiring emergency fluid replacement, inotropic support or interventional treatment; a major bleeding event was considered to be severe if the bleeding episode that led to hemodynamic compromise requiring emergency intervention or if the bleed was life-threatening or fatal.2
Over the course of five years, 1006 patients were randomized in the PEITHO trial.2 The median age was 70 years old, and all patients were normotensive at randomization. A statistically significant reduction in hemodynamic decompensation was present in the tenecteplase group (1.6% versus 5.0% with placebo, p=0.002, CI: 0.14-0.68, NNT= 33). Death from any cause at 30 days was not found to be significant between both groups (p=0.42, CI: 0.34-1.57). A total of 27 of 1005 patients underwent rescue thrombolysis, 23 of 499 from placebo group and 4 of 506 from treatment group. Additionally, the number of recurrent pulmonary emboli (between randomization and 7 days) was higher in placebo-treated patients, although this difference was not found to be statistically significant (p=0.12, CI: 0.02-1.68). However, there was also an increase in extracranial bleeding (6.3% with tenecteplase versus 1.2% with placebo, p<0.001, CI: 2.3-13.39, NNH = 20) and stroke (2.4% with tenecteplase versus 0.2% with placebo, p=0.003, CI: 1.57-93.39, NNH = 46) in the treatment group. The results of the trial were similar for all subgroup analyses tested.2
The PEITHO trial showed that while tenecteplase reduced the occurrence of hemodynamic decompensation, it also came with the price of ...