Yet, by “positive”, as we all too often see, the underlying data comes with a surprise twist.
The Pulmonary Embolism Thrombolysis (PEITHO) trial evaluates single-dose tenecteplase added to conventional heparin therapy for the treatment of “intermediate risk” acute pulmonary embolism. This includes patients with pulmonary embolism, right ventricular dysfunction on imaging, and elevated cardiac biomarkers. For the primary endpoint of death or hemodynamic deterioration within 7 days, 2.6% of patients in the immediate thrombolysis group met this outcome vs. 5.6% of patients in the usual treatment arm (OR 0.44, p=0.02).
Unfortunately, this composite outcome obfuscates the difference between treatment arms is limited solely to hemodynamic deterioration. The downside to thrombolysis – major extracranial bleeding (11.5% by ISTH definition) and hemorrhagic stroke (2.0%) – occurred five times as frequently in the treatment arm. As a result, the overall 7-day and 30-day mortality were statistically identical. Ultimately, then, this study paints the treatment decision as a choice between cardiovascular instability and life-threatening bleeding complications.
A couple interesting tidbits from the supplementary appendix:
- The criteria for myocardial injury was a troponin I >0.06 μg/L or troponin T >0.01 μg/L. These may be relatively inclusive thresholds.
- Not all placebo patients developing hemodynamic collapse received subsequent thrombolysis; likewise, almost half of those who received open-label thrombolysis had no hemodynamic collapse.
- Half the deaths in the placebo arm were “sudden unexplained” or “other”, compared with bleeding or stroke complications in the thromboysis arm.
How does this study fit in with the other recent evidence regarding thrombolysis of non-massive pulmonary embolism, e.g. MOPETT and TOPCOAT? It means we know there are patients who will benefit – both in short-term hemodynamics and long-term functional status. However, we’re still trying to minimize the number harmed by parsing out the best candidates and choosing the correct dose. There’s a lot of room for disagreement and practice variation during continued investigation, with practice ranging from standard anticoagulation and monitoring to, as Jeff Kline promotes, full-dose thrombolysis with tenecteplase. At the moment, I fall into the half-dose camp – but always re-evaluating new evidence.
“Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism”