Adding clinical markers of more severe form of intermediate-high risk pulmonary embolism improves risk stratification and possibly identifies candidates for fibrinolytic therapy
Authors: Radovanovic N , Radosavljevic-Radovanovic M , Prodanovic M , Savic Spasic L , Lojovic N , Kecman E , Djekic A 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
The authors of PEITHO study recently proposed 3 changes for future trials, in order to identify a higher-risk population among patients with intermediate-high risk PE, as potential candidates for thrombolysis: 1. longer early follow-up (30 days); 2. triple adverse composite endpoint (TACE): death, non-fatal hemodynamic collapse, or non-fatal recurrent PE; and 3. inclusion of 1 or 2 clinical indicators of PE severity, namely SBP ⩽110 mmHg or respiratory rate (RR) &gt;20 breaths/min, in addition to established clinical score, imaging and biochemical criteria.

Purposes
a.) to investigate whether these clinical markers identify pts at higher risk for 30-days TACE in our study population; b.) to define the best cut-off values of these markers, as well as other significant predictors in our population; and c.) to evaluate the effect of fibrinolytic therapy (FT) compared to heparin in this, higher risk group of pts.

Methods
From the institutional PE registry, 148 consecutive pts with intermediate-high risk PE and 30 days follow-up were identified and divided into 3 groups: group 1 – pts with SBP ⩽110 mmHg; group 2 – pts with RR &gt;20 breaths/min and group 3 – pts without any of these markers. The primary endpoint was as previously defined and the safety outcomes were updated TIMI non-CABG related bleeding. The outcome of these 3 groups of pts was compared separately, in the non-FT (heparin) group and in the FT group. For cut-off values determination, ROC analysis was used. The association of FT and 30-days outcome in the highest risk group of pts was analyzed by propensity score (PS)-adjusted Cox regression analysis.

Results
Pts in group 1 and 2, treated with heparin, had significantly higher incidence of TACE compared to patients in group 3 (p=0.033 and p=0.004, respectively). In contrast, there was no difference in TACE between 3 groups, if they were treated with FT. Also, pts in group 2 were at 4.7 times higher risk for TACE compared to group 3, if treated with heparin. The optimal cut-off value of RR in our study was 24 breaths/min. The most important predictor of TACE in our study was shock index (OR (95%CI); 4.58 (1.38-15.25)), with a cut-off value of 0,82 (sens. 95%, spec. 59%). When we tested the effect of FT (adjusted to PS) on TACE in patients with RR &gt; 24/min and shock index &gt; 0.82, we obtained significant reduction of TACE compared to pts treated with heparin (OR (95%CI); 0.30 (0.01–0.56); p = 0.027). The incidence of bleeding in our study was higher in pts treated with FT (12.9% vs 6% in the non-FT group; p=0.04), but not the major or fatal ones.

Conclusion
Patients with SBP ≤110 mmHg or RR &gt;20 breaths/min do have worse prognosis, when treated with heparin, compared to those without these clinical markers. Still, in our study, the best cut-off value of RR was higher – 24 breaths/min, and the best predictor of TACE was shock index &gt; 0.82. These pts may benefit from fibrinolytic therapy, without an increase of fatal bleeding.