J Stroke.  2024 Sep;26(3):434-445. 10.5853/jos.2024.01389.

Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study

• Salim HA
• Yedavalli V
• Musmar B
• Adeeb N
• Essibayi MA
• Naamani KE
• Henninger N
• Sundararajan SH
• Kühn AL
• Khalife J
• Ghozy S
• Scarcia L
• Tan BY
• Pulli B
• Heit JJ
• Regenhardt RW
• Cancelliere NM
• Bernstock JD
• Rouchaud A
• Fiehler J
• Sheth S
• Puri AS
• Dyzmann C
• Colasurdo M
• Barreau X
• Renieri L
• Filipe JP
• Harker P
• Radu RA
• Marotta TR
• Spears J
• Ota T
• Mowla A
• Jabbour P
• Biswas A
• Clarençon F
• Siegler JE
• Nguyen TN
• Varela R
• Baker A
• Altschul D
• Gonzalez NR
• Möhlenbruch MA
• Costalat V
• Gory B
• Stracke CP
• Aziz-Sultan MA
• Hecker C
• Shaikh H
• Liebeskind DS
• Pedicelli A
• Alexandre AM
• Tancredi I
• Faizy TD
• Kalsoum E
• Lubicz B
• Patel AB
• Pereira VM
• Guenego A
• Dmytriw AA
• the MAD MT Investigators

• KMID: 2559561
• DOI: http://doi.org/10.5853/jos.2024.01389

Abstract

Background and Purpose
The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone.
Methods
This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage.
Results
The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001).
Conclusion
The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Keyword

Stroke; Mechanical thrombectomy; Distal medium vessel occlusions

Figure

• 

  Figure 1. Patient selection and propensity score matching flowchart. mRS, modified Rankin Scale; MT, mechanical thrombectomy; IVT, intravenous thrombolysis; PSM, propensity score matching ratio. *Multipl selection of patients possible.

• 

  Figure 2. Comparative outcomes of MT-IVT versus IVT alone. (A) The percentage distribution of 90-day mRS scores for patients treated with IVT alone compared to those who received MT in addition to IVT (MT-IVT). The mRS scores range from 0 (no symptoms) to 6 (death), with the number of patients achieving each score level represented by the length of the bars along the X-axis. (B) The proportion of patients experiencing various types of hemorrhagic complications post-treatment. mRS, modified Rankin Scale; IVT, intravenous thrombolysis; MT, mechanical thrombectomy; sICH, symptomatic intracerebral hemorrhage; ICH, intracerebral hemorrhage; SAH, subarachnoid hemorrhage; HI1, hemorrhagic infarction type 1; HI2, hemorrhagic infarction type 2; PH1, parenchymal hematoma type 1; PH2, parenchymal hematoma type 2. ***P<0.001.

• 

  Figure 3. Subgroup analysis by scenario “Drip and Ship” versus “Mothership.” mRS, modified Rankin Scale; MT, mechanical thrombectomy; IVT, intravenous thrombolysis; ICH, intracerebral hemorrhage; sICH, symptomatic intracerebral hemorrhage; OR, odds ratio; CI, confidence interval.

• 

  Figure 4. Subgroup analysis by location medium versus distal. mRS, modified Rankin Scale; MT, mechanical thrombectomy; IVT, intravenous thrombolysis; ICH, intracerebral hemorrhage; sICH, symptomatic intracerebral hemorrhage; SAH, subarachnoid hemorrhage; OR, odds ratio; CI, confidence interval.

Reference

References

1. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015; 372:11–20.

2. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015; 372:2296–2306.

3. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015; 372:2285–2295.

4. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015; 372:1019–1030.

5. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016; 387:1723–1731.

6. Ospel JM, Goyal M. A review of endovascular treatment for medium vessel occlusion stroke. J Neurointerv Surg. 2021; 13:623–630.

7. Australian New Zealand Clinical Trials Registry. Trial review: trial registered on ANZCTR [Internet]. Camperdown: ANZCTR;2021. [accessed March 23, 2024]. Available from: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621001746820p.

8. Dmytriw AA, Musmar B, Salim H, Ghozy S, Siegler JE, Kobeissi H, et al. Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: a retrospective, multicenter, and multinational study. Eur Stroke J. 2024; 9:328–337.

9. Saver JL, Chapot R, Agid R, Hassan A, Jadhav AP, Liebeskind DS, et al. Thrombectomy for distal, medium vessel occlusions: a consensus statement on present knowledge and promising directions. Stroke. 2020; 51:2872–2884.

10. Sarraj A, Sangha N, Hussain MS, Wisco D, Vora N, Elijovich L, et al. Endovascular therapy for acute ischemic stroke with occlusion of the middle cerebral artery M2 segment. JAMA Neurol. 2016; 73:1291–1296.

11. Dmytriw AA, Ghozy S, Salim HA, Musmar B, Siegler JE, Kobeissi H, et al. Assessment of thrombectomy versus combined thrombolysis and thrombectomy in patients with acute ischemic stroke and medium vessel occlusion. Radiology. 2024; 312:e233041.

12. Siegler JE, Shaikh H, Khalife J, Oak S, Zhang L, Abdalkader M, et al. Aspiration versus stent-retriever as first-line endovascular therapy technique for primary medium and distal intracranial occlusions: a propensity-score matched multicenter analysis. Stroke Vasc Interv Neurol. 2023; 3:e000931.

13. Salim H, Musmar B, Adeeb N, Yedavalli V, Lakhani D, Grewal SS, et al. Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke. Eur Stroke J. 2024; May. 10. [Epub]. Available from: https://doi.org/10.1177/23969873241249295.

14. Radu RA, Costalat V, Romoli M, Musmar B, Siegler JE, Ghozy S, et al. Outcomes with general anesthesia compared to conscious sedation for endovascular treatment of medium vessel occlusions: results of an international multicentric study. Clin Neuroradiol. 2024; Apr. 30. [Epub]. Available from: https://doi.org/10.1007/s00062-024-01415-1.

15. Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019; 13(Suppl 1):S31–S34.

16. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007; 4:e296.

17. von Kummer R, Broderick JP, Campbell BC, Demchuk A, Goyal M, Hill MD, et al. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. 2015; 46:2981–2986.

18. Stuart EA. Matching methods for causal inference: a review and a look forward. Stat Sci. 2010; 25:1–21.

19. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983; 70:41–55.

20. Scheitz JF, Seiffge DJ, Tütüncü S, Gensicke H, Audebert HJ, Bonati LH, et al. Dose-related effects of statins on symptomatic intracerebral hemorrhage and outcome after thrombolysis for ischemic stroke. Stroke. 2014; 45:509–514.

21. Zinkstok SM, Engelter ST, Gensicke H, Lyrer PA, Ringleb PA, Artto V, et al. Safety of thrombolysis in stroke mimics: results from a multicenter cohort study. Stroke. 2013; 44:1080–1084.

22. Engelter ST, Soinne L, Ringleb P, Sarikaya H, Bordet R, Berrouschot J, et al. IV thrombolysis and statins. Neurology. 2011; 77:888–895.

23. Rubin DB. Multiple imputation. In : van Buuren S, editor. Flexible imputation of missing data. 2nd ed. New York: Chapman and Hall/CRC;2018. p. 29–62.

24. Goyal M, Ospel JM, Menon BK, Hill MD. MeVO: the next frontier? J Neurointerv Surg. 2020; 12:545–547.

25. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019; 50:e344–e418.

26. Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, et al. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic Stroke. J Neurointerv Surg. 2023; 15:e8.

27. Loh EW, Toh KZX, Kwok GYR, Teo YH, Teo YN, Goh C, et al. Endovascular therapy for acute ischemic stroke with distal medium vessel occlusion: a systematic review and meta-analysis. J Neurointerv Surg. 2023; 15:e452–e459.

28. Saber H, Desai SM, Haussen D, Al-Bayati A, Majidi S, Mocco J, et al. Endovascular therapy vs medical management for patients with acute stroke with medium vessel occlusion in the anterior circulation. JAMA Netw Open. 2022; 5:e2238154.

29. Grossberg JA, Rebello LC, Haussen DC, Bouslama M, Bowen M, Barreira CM, et al. Beyond large vessel occlusion strokes: distal occlusion thrombectomy. Stroke. 2018; 49:1662–1668.

30. Rizzo F, Romoli M, Simonetti L, Gentile M, Forlivesi S, Piccolo L, et al. Reperfusion strategies in stroke with medium-to-distal vessel occlusion: a prospective observational study. Neurol Sci. 2024; 45:1129–1134.

31. Strambo D, Bartolini B, Beaud V, Marto JP, Sirimarco G, Dunet V, et al. Thrombectomy and thrombolysis of isolated posterior cerebral artery occlusion: cognitive, visual, and disability outcomes. Stroke. 2020; 51:254–261.

32. Saber H, Narayanan S, Palla M, Saver JL, Nogueira RG, Yoo AJ, et al. Mechanical thrombectomy for acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery: a meta-analysis. J Neurointerv Surg. 2018; 10:620–624.

33. Nogueira RG, Zaidat OO, Castonguay AC, Haussen DC, Martin CO, Holloway WE, et al. Rescue thrombectomy in large vessel occlusion strokes leads to better outcomes than intravenous thrombolysis alone: a ‘real world’ applicability of the recent trials. Interv Neurol. 2016; 5:101–110.

34. Sarraj A, Hassan A, Savitz SI, Grotta JC, Cai C, Parsha KN, et al. Endovascular thrombectomy for mild strokes: how low should we go? Stroke. 2018; 49:2398–2405.

35. Sarraj A, Grotta J, Albers GW, Hassan AE, Blackburn S, Day A, et al. Clinical and neuroimaging outcomes of direct thrombectomy vs bridging therapy in large vessel occlusion: analysis of the SELECT cohort study. Neurology. 2021; 96:e2839–e2853.

36. Katsanos AH, Sarraj A, Froehler M, Purrucker J, Goyal N, Regenhardt RW, et al. IV thrombolysis initiated before transfer for endovascular stroke thrombectomy: a systematic review and meta-analysis. Neurology. 2023; 100:e1436–e1443.

37. Khatri P, Kleindorfer DO, Devlin T, Sawyer RN Jr, Starr M, Mejilla J, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA. 2018; 320:156–166.

38. Chen HS, Cui Y, Zhou ZH, Zhang H, Wang LX, Wang WZ, et al. Dual antiplatelet therapy vs alteplase for patients with minor nondisabling acute ischemic stroke: the ARAMIS randomized clinical trial. JAMA. 2023; 329:2135–2144.