By Giuseppe Reale, MD. Department of Geriatrics, Neurosciences and Orthopaedics, Università Cattolica del Sacro Cuore, Rome, Italy

Approximately 20% of all ischemic strokes are due to large vessel occlusion (LVO)1 and the current guidelines recommend intravenous thrombolysis prior to endovascular treatment in LVO stroke patients23. However, alteplase has an early recanalization rate of less than 50%4, which is even lower in case of LVO. Considering that early reperfusion is a strong predictor of good outcome5, several Authors have pointed out that fast, direct thrombectomy might be sufficient to achieve good outcomes, considering that many patients otherwise ineligible for IVT have excellent results with mechanical thrombectomy alone6. A recent trial, DIRECT-MT, showed non-inferiority of direct thrombectomy vs bridging thrombolysis plus thrombectomy in LVO strokes7. However, the trial had a very large margin of non-inferiority, while further similar trials are still ongoing.

In the meantime, many Authors have tried to disentangle this burning topic, performing metanalyses of studies published until 2017, with conflicting results8–10.

In this view, a metanalysis recently published on Stroke tried to shed a new light on the debate, combining the results of trials published before 2017 with those of the latest ones11.

The metanalysis included 30 trials, with 7191 patients in the combination group and 4891 patients in the thrombectomy alone group. The Authors found that patients from the combination group had better clinical outcome and lower mortality than the direct thrombectomy group, despite of no difference in terms of recanalization. Regarding safety, there was no statistically significant difference in terms of hemorrhagic complications between groups. The differences were still relevant when analyzing the subgroup of IVT-eligible patients, being arguable that patients IVT-ineligible who underwent direct thrombectomy had delayed presentation, high onset-to-groin time and hemorrhagic diathesis.

These results open further debate on stroke network organization and even the use of new thrombolytic agents, such as tenecteplase. Hopefully, ongoing trials will find definitive answers to this hot question.

P.S. While writing this post, two new non-inferiority trials on direct thrombectomy were published (DEVT and SKIP), confirming how stroke research is magmatic and relentless12. The debate is still open.


  1. Rai AT, Seldon AE, Boo S, Link PS, Domico JR, Tarabishy AR, Lucke-Wold N, Carpenter JS. A population-based incidence of acute large vessel occlusions and thrombectomy eligible patients indicates significant potential for growth of endovascular stroke therapy in the USA. J Neurointerv Surg. 2017;9:722–726.
  2. Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, Schellinger PD, Toni D, de Vries J, White P, et al. European Stroke Organisation (ESO) – European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischaemic StrokeEndorsed by Stroke Alliance for Europe (SAFE). European Stroke Journal. 2019;4:6–12.
  3. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, 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. Available from:
  4. Bhatia R, Hill MD, Shobha N, Menon B, Bal S, Kochar P, Watson T, Goyal M, Demchuk AM. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke. 2010;41:2254–2258.
  5. Rha J-H, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007;38:967–973.
  6. Fischer U, Kaesmacher J, Mendes Pereira V, Chapot R, Siddiqui AH, Froehler MT, Cognard C, Furlan AJ, Saver JL, Gralla J. Direct Mechanical Thrombectomy Versus Combined Intravenous and Mechanical Thrombectomy in Large-Artery Anterior Circulation Stroke: A Topical Review. Stroke. 2017;48:2912–2918.
  7. Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, Peng Y, Han H, Wang J, Wang S, et al. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020;382:1981–1993.
  8. Phan K, Dmytriw AA, Maingard J, Asadi H, Griessenauer CJ, Ng W, Kewagamang K, Mobbs RJ, Moore JM, Ogilvy CS, et al. Endovascular Thrombectomy Alone versus Combined with Intravenous Thrombolysis. World Neurosurg. 2017;108:850-858.e2.
  9. Ea M, Am M, Mo N, Rv C, Rf J, Jj V, Mr F. Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in Stroke Patients: A Meta-Analysis. Stroke. 2017;48:2450–2456.
  10. Kaesmacher J, Mordasini P, Arnold M, López-Cancio E, Cerdá N, Boeckh-Behrens T, Kleine JF, Goyal M, Hill MD, Pereira VM, et al. Direct mechanical thrombectomy in tPA-ineligible and -eligible patients versus the bridging approach: a meta-analysis. J Neurointerv Surg. 2019;11:20–27.
  11. Wang Yuting, Wu Xiao, Zhu Chengcheng, Mossa-Basha Mahmud, Malhotra Ajay. Bridging Thrombolysis Achieved Better Outcomes Than Direct Thrombectomy After Large Vessel Occlusion. Stroke. 2021;52:356–365.
  12. Intravenous Thrombolysis Before Endovascular Thrombectomy for Acute Ischemic Stroke | Cerebrovascular Disease | JAMA | JAMA Network . ;Available from: