We have MOPETT, PEITHO, and now, TOPCOAT.
MOPETT looked at 121 patients, and found that tpa led to a decrease in pulmonary hypertension (22 vs 8 mm Hg) at 28 month follow up, and a decreased LOS (2.2 vs 4.9 days). This drew some backlash and claims that there was an unusually high incidence of pulmonary HTN in this trial.
PEITHO looked at 1,005 patients, with “intermediate risk” which they defined as RV strain on echo or CT, plus a positive troponin. Patients were randomized to weight based tenecteplase as a bolus + standard anticoagulation vs standard anticoagulation only. Essentially, death at 7 & 30 days were similar – 1.2% vs 1.8% (lytics vs no lytics) at 7 days and 2.4% vs 3.2% at 30 days (lytics vs no lytics). Stroke at 7 days was 2.4% in the lytic treatment arm vs 0.2% without lytics, while hemodynamic compromise defined as persistent hypotension, pressor requirements, intubation and CPR, was higher in the no lytics group (1.6% vs 5%). They make no mention of pulmonary hypertension at follow up. So really, the patient has a 3% chance of death either way.
Now, there is TOPCOAT. Normotensive patients with PE and RV strain (either on echo or BNP), were given either tenecteplase bolus + standard anticoagulation or standard anticoagulation only. The study, unfortunately, enrolled only 83 patients, with 40 receiving tenecteplase. 16 non-lytic patients vs 6 lytic patients had an adverse outcome, defined as death, shock, intubation, major bleeding within 5 days, recurrent PE, poor functional capacity (RV dysfunction + dyspnea at rest or exercise intolerance), or an SF36 Physical component score <30 at 90 day follow up. Basically, since only 1 patient died and 2 required intubation of the 16 non-lytic patients, the main difference here is functional capacity and quality of life. More on SF36 here: http://www.sf-36.org, though it is essentially a composite score measuring quality of life).
For submassive PE’s, the general trend is that a shared decision will need to be made: mortality is essentially the same, 2-3%, no matter the treatment. Would they rather it be from PE or from its treatment, but knowing that they have a chance at better quality of life months to years down the line? There are potential legal landmines on either side of this discussion. Document well, my friends!
Unusually high incidence of pulmonary hypertension in MOPETT trial. PMID: 23764652
Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial). PMID: 23102885
Fibrinolysis for patients with intermediate-risk pulmonary embolism. PMID: 24716681
Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at three months (TOPCOAT): Multicenter double-blind, placebo-controlled randomized trial. PMID: 24484241