Direct Mechanical Thrombectomy Versus Combined Intravenous and Mechanical Thrombectomy in Large-Artery Anterior Circulation Stroke
2017; Lippincott Williams & Wilkins; Volume: 48; Issue: 10 Linguagem: Inglês
10.1161/strokeaha.117.017208
ISSN1524-4628
AutoresUrs Fischer, Johannes Kaesmacher, Vítor Mendes Pereira, René Chapot, Adnan H. Siddiqui, Michael T. Froehler, Christophe Cognard, Anthony J. Furlan, Jeffrey L. Saver, Jan Gralla,
Tópico(s)Cerebrovascular and Carotid Artery Diseases
ResumoHomeStrokeVol. 48, No. 10Direct Mechanical Thrombectomy Versus Combined Intravenous and Mechanical Thrombectomy in Large-Artery Anterior Circulation Stroke Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessReview ArticlePDF/EPUBDirect Mechanical Thrombectomy Versus Combined Intravenous and Mechanical Thrombectomy in Large-Artery Anterior Circulation StrokeA Topical Review Urs Fischer, MD, MSc, Johannes Kaesmacher, MD, Vitor Mendes Pereira, MD, René Chapot, MD, Adnan H. Siddiqui, MD, Michael T. Froehler, MD, PhD, Christoph Cognard, MD, Anthony J. Furlan, PhD, Jeffrey L. Saver, MD and Jan Gralla, MD, MSc Urs FischerUrs Fischer From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). , Johannes KaesmacherJohannes Kaesmacher From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). , Vitor Mendes PereiraVitor Mendes Pereira From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). , René ChapotRené Chapot From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). , Adnan H. SiddiquiAdnan H. Siddiqui From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). , Michael T. FroehlerMichael T. Froehler From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). , Christoph CognardChristoph Cognard From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). , Anthony J. FurlanAnthony J. Furlan From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). , Jeffrey L. SaverJeffrey L. Saver From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). and Jan GrallaJan Gralla From the Department of Neurology (U.F.), and Department of Diagnostic and Interventional Neuroradiology (J.G.), Inselspital, University Hospital Bern, Switzerland; University of Bern, Switzerland (U.F., J.G.); Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, Germany (J.K.); Division of Neuroradiology, Department of Medical Imaging (V.M.P.) and Division of Neurosurgery, Department of Surgery (V.M.P.), Toronto Western Hospital, University Health Network, Ontario, Canada; Department of Radiology and Neuroradiology, Alfried Krupp Krankenhaus Essen, Germany (R.C.); Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (A.S.); Vanderbilt University Medical Center, Nashville, TN (M.F.); Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, France (C.C.); University Hospitals Case Medical Center, Neurological Institute, Case Western Reserve University, Cleveland, OH (A.F.); and UCLA Comprehensive Stroke Center, Geffen School of Medicine at UCLA, University of California, Los Angeles (J.L.S). Originally published8 Sep 2017https://doi.org/10.1161/STROKEAHA.117.017208Stroke. 2017;48:2912–2918Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2017: Previous Version 1 Intravenous thrombolysis (IVT) with recombinant intravenous (IV) tPA (tissue-type plasminogen activator) significantly improves the odds of good outcome after ischemic stroke when delivered within 4.5 hours of stroke onset, irrespective of age and over a broad range of stroke severity, and despite an increased risk of intracranial hemorrhage (ICH).1 Therefore, in the absence of contraindications, IVT is the standard therapy for all patients presenting with an acute ischemic stroke (AIS) within 4.5 hours after symptom onset.2 However, IVT has some important limitations, such as a narrow time window with a rapidly decreasing efficacy and a rapidly increasing number needed to treat,1 the overall increase of fatal ICH compared with placebo,1 a poor recanalization rate in patients with large thrombus burden,3 and various contraindications, such as pretreatment with oral anticoagulants and unclear time of symptom onset.Endovascular stroke treatment (EVT) in combination with IVT (ie, bridging thrombolysis) has the potential to overcome some limitations of IVT, especially the poor recanalization rate of patients with large vessel occlusions (LVOs). Three randomized controlled trials (RCTs) published in 2013 failed to demonstrate superior clinical outcomes of EVT.4–6 However, since December 2014, 8 RCTs testing newer devices have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (with and without IV tPA) improves outcome in anterior circulation (AC) ischemic stroke patients with LVO compared with best medical treatment alone.7–14 These later trials used second-generation devices, required imaging confirmation of LVO, emphasized rapid time to reperfusion, and excluded patients with a priori high chance of futile recanalization (ie, patients with large areas of brain tissue who had already undergone infraction or patients with poor collaterals). MT with stent retriever in addition to IVT is now the recommended treatment for AIS patients with LVO based on class I level A evidence.15,16 Because all IVT-eligible patients with LVO in the pivotal trials received IVT before undergoing randomized MT or control treatment, current American and European recommendations advocate that IVT should be offered to all eligible patients with LVO before MT.15,16The positive trials also demonstrated that MT alone is an effective therapy for acute ischemic stroke, improving outcomes among patients ineligible for IV tPA.17 Whether MT alone is as good, worse, or better than pretreatment with IV tPA before MT among IVT-eligible AIS patients with LVO in the AC has now become a matter of debate. This topical review addresses this question, summarizing evidence in favor and against treatment with IV tPA before MT in patients with LVO in the AC.Arguments in Favor of Bridging ThrombolysisEarly ReperfusionIVT can be started earlier than MT, and in some patients, IV tPA might completely lyse proximal occlusions before MT starts. A recent meta-analysis found a complete recanalization within 3 hours after application of IV tPA in 21% of M1 occlusions, in 38% of M2 occlusions, and in 4% of internal carotid artery (ICA) occlusions.18 However, in clinical practice, recanalization may not occur early enough to obviate the need for subsequent MT. A recent study analyzed early recanalization rates after IVT and before EVT in bridging patients.19 Relevant recanalization rates before EVT in bridging patients were dependent on the occlusion site: 19 patients with ICA occlusions or 12 patients with M1 occlusions had to be treated with IVT before EVT to achieve one relevant recanalization before EVT, whereas in M2 occlusions, the number needed to treat was 6.19 Furthermore, recanalization rates were lower in mothership than in drip-and-ship patients: only 3.8% versus 7.3% of ICA occlusions, 5.9% versus 12.8% of M1 occlusions, and 9.5% versus 30.8% of M2 occlusions had a relevant early recanalization.19 The higher recanalization rates in drip-and-ship patients compared with mothership patients are most likely because of a longer exposure time to tPA. This has major implications on outcome because early recanalization is clearly related with a favorable outcome.1 Therefore, according to current evidence, all patients in the drip-and-ship model should be pretreated with IVT.Early recanalization was also observed in the pivotal trials of EVT. In REVASCAT (The Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset), patients were randomized only if an arterial occlusion persisted 30 minutes after administration of IV tPA infusion, but in the other initial 4 trials (MR CLEAN [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], SWIFT PRIME [Solitaire™ With the Intention for Thrombectomy as Primary Endovascular Treatment Trial], EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits — Intra-Arterial Trial], and ESCAPE [Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial]), MT was started as soon as possible after randomization.7–11 Even though recanalization rates before MT reported in the REVASCAT trial (7.1%) may be biased because only IV tPA nonresponders were included, rates were also low in the MR CLEAN (7.9%), SWIFT PRIME (7.1%), EXTEND-IA (14.3%), and ESCAPE (6.7%) trials.7–11 Of note, some of the aforementioned numbers (for REVASCAT, MR CLEAN, and ESCAPE) are calculated assuming that all recanalizations revealed on first angiography runs and all clinical improvements obviating the need for MT (despite allocated to the intervention arm) occurred in patients receiving IVT.7,9,11 It is also important to consider that recanalization rates before MT were low, despite the fact that the majority of patients had middle cerebral artery occlusions and many patients were treated in a drip-and-ship fashion. In addition, a small study by Rai et al20 described similar rates of preinterventional recanalization rates in patients with and without preceding administration of IV tPA, 5.8% (3/52) versus 5.3% (2/38) for spontaneous versus IV tPA associated, respectively.In summary, preinterventional recanalization rates are relatively low (7.7% for pooled recanalization rates of the RCTs), are dependent on the occlusion site with low rates in ICA and M1 occlusions, and seem to be dependent on the exposure time to tPA. Further studies are required to compare rates of preinterventional lysis in patients receiving IV tPA to those ineligible for IV tPA.Thrombus Softening and Facilitation of Successful ReperfusionIt has been hypothesized that IVT before MT may increase recanalization rates and facilitate the endovascular procedure by softening the thrombus and, thus, reduce the duration of the procedure with fewer passes of stent retrievers. However, there is a considerable between-study variance whether IV tPA facilitates successful and faster reperfusion in subsequent EVT.20–25 Observations suggesting a positive effect are mainly derived from small single-center retrospective cohort studies and are not supported by post hoc analyses of recent RCTs.26,27 Better recanalization rates were not observed in patients pretreated with IV tPA in a pooled post hoc analysis of SWIFT PRIME and STAR (Solitaire Flow Restoration Thrombectomy for Acute Revascularization), nor a post hoc analysis of MR CLEAN.26,27 It is also important to keep 2 further considerations in mind: first, softening of thrombi may induce increased clot fragility, which can encourage fragmentation and distal embolization at MT, lowering the rate of Thrombolysis In Cerebral Infarction (TICI) 3 reperfusions, thus, diminishing the clinical benefit.28 Second, lower recanalization rates in patients ineligible for IV tPA may be an epiphenomenon of different clot histology and clot characteristics. Patients ineligible for medical treatment are more likely to have thrombi of cardiogenic origin.25,29 These cardiogenic thrombi were found to have a higher fibrin content, which is associated with lower rates of successful reperfusion.30–33 Considering the neutral results of post hoc RCTs, the potential difference in clot characteristics and the likelihood of publication bias, the evidence that IV tPA actually promotes good angiographic reperfusion results is rather low. However, further prospective studies should compare recanalization rates in patients with and without IVT before EVT.Recanalization Rates in Patients With MT FailureIn a small cohort of patients, MT may be delayed or simply not feasible because of the impossibility to achieve arterial access or to reach the target occlusion. In SWIFT PRIME, arterial access was not possible in 2% of patients; in EXTEND-IA in 2.9%; in ESCAPE in 3.6%; in MR CLEAN in 5%; and in REVASCAT, information was not provided.7–11 IVT offers a chance of reperfusion if thrombectomy is aborted. However, whether IVT significantly increases the odds of favorable outcome in this particular subset of patients has not yet been assessed. Furthermore, it is increasingly feasible to use transbrachial or direct carotid alternative arterial access routes, if femoral access is not possible.Reperfusion of Remaining Distal Occlusions After MTIV tPA may help to recanalize thrombi in small arteries and in the microvasculature, which are inaccessible for thrombectomy devices, increasing achievement of complete reperfusion.34 This may have relevant clinical implications because TICI 3 reperfusions are associated with less neurological deficits and better functional outcome.35,36 It has been shown that most distal branch occlusions leading to incomplete reperfusions are not present before MT but commonly occur during endovascular treatment.37 However, this potential benefit is constrained by the low proportion of patients who still have a running IV tPA infusion at the time of TICI 2b reperfusion, allowing IV tPA to access distal emboli. Considering the median IV tPA administration to first reperfusion intervals reported in the RCTs, IV tPA infusions have usually already ended when substantial reperfusion is achieved. Therefore, concentrations of circulating tPA may already be relatively low because tPA has a comparatively short half-life of 5 to 10 minutes in the human blood. Withholding IV r-tPA before thrombectomy may open the door for tailored medical reperfusion strategies: IV r-tPA could then be selectively administered during or after EVT in patients with incomplete reperfusion (<TICI 3), ensuring that therapeutic concentrations are reached when needed.Arguments Against Bridging ThrombolysisRecanalization RatesIVT is not effective in the vast majority of patients with LVO with a large thrombus burden. Patients with LVO in the ICA and M1 segment of the middle cerebral artery treated with IVT have low recanalization rates.3,38,39 If IV tPA will provide little benefit in these patients, the risks it confers become more unacceptable.SafetyFrom a safety perspective, IV tPA increases the risk of symptomatic and asymptomatic ICH, as well as systemic and arterial access bleeding complications compared with placebo.1,40 In the pivotal MT RCTs, hemorrhage rates were not higher in the endovascular than nonendovascular group, suggesting that the great preponderance of the bleeding complications in patients with MT plus IVT were related to IV tPA rather than to MT.17 Intravenous tPA is much more strongly associated with vessel injury and blood-barrier disruption than MT alone.41,42 Especially in patients with a high risk of ICH after IVT, such as patients with early infarct signs, microbleeds, extensive leukoaraiosis, high baseline National Institutes of Health stroke scale scores, high baseline glucose values, and older age, the bleeding risk of IV tPA may exceed the potential benefit.43,44Peri-Interventional TechniquesIVT limits additional procedures during EVT: administration of antiplatelet agents is contraindicated after IV tPA but potentially beneficial after endovascular intervention and clearly indicated when stenting has to be performed during the endovascular procedure. Furthermore, in rare situations, heparin or glycoprotein IIb/IIIa receptor antagonists may be necessary to treat ongoing thrombus formation. Besides, future development of MT may include treatment in more distal vessels, where the risk of ICH may be increased by the smaller diameter of the arteries. In these patients, IVT may potentiate the risks.Thrombus Fragility and Thrombus MigrationPeriprocedural thrombus fragmentation is a relevant risk in EVT. In a small retrospective analysis, bridging thrombolysis was associated with an increased risk of distal emboli.45 IV tPA may induce migration of thrombi from proximal into distal vessels, where MT is no longer possible, converting a treatable LVO into an untreatable medium vessel occlusion. How much IV tPA facilitates the risk of thrombus migration over the spontaneous rate is currently a matter of debate.46 Similarly, IV tPA may also lyse thrombi in the left atrial appendage or in other proximal sources, precipitating new thromboemboli. However, prospective studies comparing thrombus migration after IVT with patients receiving no treatment are lacking.Other ConsiderationsIn the United States, IV tPA has also a considerable impact on costs: according to Rai et al,20 100 mg vial of alteplase (Activase; Genentech, San Francisco, CA) used in the preparation of an IV dose for stroke thrombolysis costs $7800. In their analysis, costs of combined MT and IVT were considerably higher than MT alone.20Administration of IV tPA before endovascular clot retrieval is an important argument to support the drip-and-ship model; however, MT in drip-and-ship patients is delayed compared with mothership patients. And even in centers where patients can be quickly moved to the endovascular suite administration of IV tPA may delay MT. Finally, IV tPA causes some rare side effects, such as life-threatening orolingual angioedema.Table summarizes the potential harms and benefits with IV tPA administration before MT.Table. Pros and Cons of Bridging TherapyPotential benefitEffect Early reperfusion at first angiography run (5%–10%), especially if short thrombi or residual flow High rates of excellent clinical outcome for this subpopulation Thrombus softening and facilitation of successful reperfusion Fewer passes of stent devices/less cost, shorter procedure time, and better outcomes Chance of reperfusion when no EVT access to thrombus possible Higher proportion with early reperfusion translating to better outcomes Reperfusion of remaining distal occlusions after mechanical thrombectomy Potential better outcomes since more complete reperfusion (TICI 3) and less severe capillary microthrombosisPotential harmEffect IV tPA-related local and systemic bleeding complications Puncture-site hematoma (1%–2%) and major systemic bleeding (1%) IV tPA-related coagulopathy and small vessel fragility More large symptomatic extraischemic parenchymal hemorrhage (1%–2%) IV tPA-related coagulopathy and sICH in patients at risk Higher rates of sICH and aICH with poor functional outcome IV tPA-related blood–brain barrier breakdown, coagulopathy, and potentiated large vessel damage because of stent retrievers Increased symptomatic parenchymal hemorrhage when infarct. Poorer functional outcome and increased infarct volume Tandem extracranial and intracranial occlusions may require additional procedures during EVT and potentially immediate antiplatelet therapy Increased symptomatic intracranial hemorrhage (10%) Distal thrombus migration Inability to retrieve thrombus with MT. Neurological deterioration and more severe/extensive ischemia Increase thrombus fragility by softening the thrombus Higher rates of peri-interventional thrombus fragmentation leading to lower rates of complete (TICI 3) reperfusions IV tPA lysis of left atrial appendage or other proximal thrombus Early stroke recurrence or multiple systemic emboli Delay to MT initiation Later median onset to reperfusion resulting in worse outcomes IV tPA-associated allergic reactions (1%) During IV tPA infusion/EVT procedure, which may worsen ischemia or require intubation/prolonged ICU stay IV tPA-related neurotoxicity in animal models More neuronal loss IV tPA cost Adds to procedural costReprinted from Chandra et al47 with permission of the publisher. Copyright ©. Authorization for this adaptation has been obtained both from the owner of the copyright in the original work and from the owner of copyright in the
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