Thrombolytic therapy for acute pulmonary embolism (PE) may benefit massive or high-risk PE. However, that strategy should not include individuals suffering from hemodynamically stable intermediate-risk PE with right ventricular dysfunction. Based on the PEIHO trial, the largest randomized controlled trial to date for intermediate-risk PE, mortality at day seven and day 28 were not different in patients who received t-PA (thrombolysis) versus those who didn't. The significant bleeding, including intracranial hemorrhage risk, was higher in patients treated with thrombolysis. One important point to note about the PEITHO trial is that the mortality in both arms was low, ranging from 2-3%. 

While treating patients with intermediate-risk, we should focus on certain factors that might be predictors of higher mortality (probably much higher than found during the PEITHO trial). Those patients may get the benefit of thrombolysis compared to conventional anticoagulation treatment. These can be easily remembered by the mnemonic “4D.” Currently, there are no studies about the usefulness of thrombolysis in these groups of patients, but these patients should be monitored closely for possible needs of thrombolysis. 

1. Diameter of RV and RV/LV ratio: RV/LV ratio >1.4. In Fasullo's study, group mortality was 17% in the control arm, and the mean RV/LV ratio was >1.4. Similarly, in a study by van der Meer, when RV/LV ratio was >1.5, mortality was 17% 
2. DVT: Patients of PE with concomitant proximal DVT may have higher mortality. In a recent study, patients with concomitant proximal DVT had 8.6% mortality compared to a patient with distal DVT (1.6%) or no DVT (1.4%) 
3. Data: PEITHO investigators did post-hoc analysis for the patients who might have got benefit from thrombolysis. Based on those data, if the patient had one or more of the following criteria, they might have the possible use of thrombolysis: SBP<110, Respiratory rate>20, history of chronic heart failure or active cancer. PEITHO-3 study is currently enrolling patients with these characteristics to understand the effect of thrombolysis. 
4. Deterioration: If patients have hemodynamic deterioration and become hypotensive (SBP<90), they will be classified as high-risk patients, and thrombolysis will be indicated. Of note, 2019 ESC/ERS guidelines mentioned that if patients have >40 mm drop in systolic pressure compared to their baseline and sustain for >15 minutes, they should be offered rescue thrombolysis. Moores and colleagues studied that deterioration in PESI score or s-PESI score at 48-72 hours was also associated with 12% or higher mortality.

Dr. Dalal is employed by Beaumont Health, he has no conflicts of interest to report.

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