IVT Bridging Therapy Outperforms Mechanical Thrombectomy in Reducing Thrombus, Clot Size

The use of intravenous thrombolysis prior to mechanical thrombectomy resulted in significantly smaller clots and significantly lower number of fragments than MT therapy alone.

A comparator study evaluating patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT), or bridging therapy, showed significant reductions in thrombus size compared to those who underwent MT alone.

Mechanically extracted thrombi were collected from 1000 patients with AIS, who were treated with either bridging therapy (n = 451; 45%) or MT alone (n = 549; 55%). Using Extracted Clot Area (ECA), investigators found that patients who underwent the bridging therapy to have statistically significantly smaller clots than those retrieved from patients treated with MT alone (median ECA, 32.7 mm2 [95% CI, 14.8-64.9] vs 36.8 mm2 [95% CI, 20.1-79.8]; P = .006). Furthermore, these patients also were associated with a significantly lower number of fragments compared to MT alone (2 [IQ1-IQ3, 1-4] vs 3 [IQ1-IQ3, 2-5]; H1 = 4.058; P = .044).

"Our findings show that IVT administration, even when it does not result in the complete dissolution of the occlusive thrombi, will reduce clot size," senior author Karen M. Doyle, BSc, PhD, Department of Physiology, Galway Neuroscience Center, University of Ireland Galway, and colleagues wrote. "Our findings also suggest that fibrinolytic activity of IVT causes a proportional decrease of the 3 main histological clot components, maintaining the percentage ratio of main components within the clot. However, we acknowledge that we have no information of clot composition before mechanical thrombectomy, which would be needed for confirmation."

Doyle et al investigated effects of each therapeutic method on histological composition of thrombi, both in terms of percentage composition and as a function of clot size. Patients were pulled from the RESTORE registry, which is aimed at analyzing clots from patients with AIS and correlating clot characteristics with clinical and procedural information.

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Using Martius Scarlett Blue stain, investigators observed no differences between the 2 groups on main histological components. Median red blood cell (RBC) composition was 45% (IQ1-IQ3, 28%-59%) for bridging therapy and 44% (IQ1-IQ3, 26%-62%) for MT alone clots (H1 = 0.018; P = .895); median fibrin (FIB) composition was 30% (IQ1-IQ3, 21%-40%) for bridging therapy and 29% (IQ1-IQ3, 19%-41%) for MT alone (H1 = 0.552; P = .458); median platelet (PTL) composition was 16% (IQ1-IQ3, 9%-30%) for bridging therapy and 17% (IQ1-IQ3, 9%-28%) for MT alone (H1 = 0.014; P = .905).

Despite not reaching statistical significance, a further analysis expressing components per clot area showed lower amounts of RBCs in those treated with bridging therapy compared to MT-only clots (median ECAxRBC, 13.25 mm2 [IQ1-IQ3, 4.29-32.06] vs 14.97 mm2 [IQ1-IQ3, 4.93-39.80]; H1 = 3.637; P = .056). Additionally, the amount of FIB and PTL was statistically significantly lower in clots for those on bridging therapy compared to MT-only clots (median ECA x FIB, 9.10 mm2 [IQ1-IQ3, 4.62-17.98] vs 10.54 mm2 [IQ1-IQ3, 5.57-22.48]; H1 = 7.920; P = .005 and median ECA x PTL, 5.04 mm2 [IQ1-IQ3, 2.26-11.32] vs 6.54 mm2 [IQ1-IQ3, 2.94-13.79]; H1 = 9.380; P = .0002, respectively).

Identified at the beginning of the procedure, 88% (n = 881) of cases had ischemic territory located in the anterior circulation, 10% (n = 100) located in the posterior circulation, and 2% (n = 17) had both anterior and posterior territories involved. Between the bridging therapy and MT alone groups, investigators found no significant difference in occlusion type (anterior/posterior occlusion: X2 = 4.575, P = .102; singular/multiple occlusion: X2 = .061; P = .804).

Doyle et al noted that, "the main strength of this study is the large patient population analyzed, arising from 4 dedicated stroke centers in Europe and analyzed by a specialized core laboratory, which gives robustness to our findings."

REFERENCE
Rossi R, Molina S, Mereuta OM, et al. Does prior administration of rtPA influence acute ischemic stroke clot composition? Findings from the analysis of clots retrieved with mechanical thrombectomy from the RESTORE registry. J Neurol. Published online August 20, 2021. doi:10.1007/s00415-021-10758-5