thrombectomy

hidden

Should interventional cardiologists perform thrombectomy?

Miguel Quintero-Consuegra, MD

“Sutor, ne ultra crepidam” a Latin expression for shoemakers not beyond the shoe, a common saying to warn people to avoid passing a judgment beyond their expertise.

With mechanical thrombectomy changing the management of stroke and becoming the standard of care for patients with large vessel occlusion (LVO), a new challenge has emerged, adequate access for care.

A recent cross-sectional study by Aldstadt et al.1 aimed to determine the percentage of the US population with 60 min (ground or air) to a designated or non-designated endovascular capable stroke center, or percentage of non-designated endovascular centers that were 30 min from an endovascular capable center.  They reported that overall a 49.6% of the US population is within 60 min of an endovascular capable stroke center, while 37% of the US population lacked access to endovascular capable centers within 60 min. For the non-endovascular stroke centers, 84% have access within 60 min, and 45.4% are within 30 min drive from an endovascular capable stroke center.

Since time is the brain, increasing the access to care is of paramount importance and increasing the number of well-trained physicians equipped to perform and treat stroke holistically.  Since there are approximately 10 times more interventional cardiologists, radiologists, and vascular surgeons than neuro interventionalist in the USA (10.000 vs. 800-1000)2, some non-endovascular capable hospitals have explored the option of incorporating some of this workforce to contribute to patient care.

Some retrospective studies3 with low sample sizes have described that their interventional cardiologist team was able to perform a thrombectomy safely, with the guidance of a stroke neurologist. Nonetheless, they are not clear on the prior training these cardiologists have had regarding neurovasculature, the nuances of the procedure, critical care, and stroke neurology.

Endovascular Neurosurgery and Interventional Neuroradiology is a field shared by physicians with different backgrounds in training, such as neurosurgeons, neurologists, and interventional radiologists. Regardless of their background or training, they are all required to complete an additional 1-2 years of training exclusively for neurointervention. Endovascular physicians trained rigorously per ACGME4 requirements were most of the physicians involved in the clinical trials (ESCAPE and DAWN) and maintained a high caseload volume of thrombectomy. The cumulative case volume is crucial since it has been associated independently for obtaining good recanalization and outcomes.5

Even if the technical aspects have various similarities between the endovascular fields, shoemakers not beyond the shoe, cannot be translated from one field to another without proper training. To adduce that interventionalist cardiologist can inherently treat intracranial diseases would be, in my opinion, not in benefit of the care of the patient, even if they are the only option nearby where no endovascular treating center can be reached, the patient outcome of patients is directly correlated with the expertise of the treating physician.

Nonetheless, interventional cardiologists should only be allowed to perform thrombectomies if they complete a full endovascular fellowship with the requirements established by the ACGME and as the other specialties go through (interventional radiology, neurosurgery, and neurology). This formal training could contribute to those rural areas where there is no possibility to access an endovascular center. More efforts should be made to increase access to endovascular capable stroke centers, to continue training neurosurgeons, radiologists, and neurologists to meet patients’ demands requiring this life-saving treatment.  But I don’t consider converting specialists in treating myocardial infarctions to stroke being a priority in the US.

REFERENCE

  1. Aldstadt J, Waqas M, Yasumiishi M, et al. Mapping access to endovascular stroke care in the USA and implications for transport models. Journal of NeuroInterventional Surgery. 2021:neurintsurg-2020-016942.
  2. Hopkins LN, Holmes DR. Public Health Urgency Created by the Success of Mechanical Thrombectomy Studies in Stroke. Circulation. 2017;135(13):1188-1190.
  3. Hornung M, Bertog SC, Grunwald I, et al. Acute Stroke Interventions Performed by Cardiologists: Initial Experience in a Single Center. JACC Cardiovasc Interv. 2019;12(17):1703-1710.
  4. Hussain S, Fiorella D, Mocco J, et al. In defense of our patients. J Neurointerv Surg. 2017;9(6):525-526.
  5. Kim BM, Baek J-H, Heo JH, Kim DJ, Nam HS, Kim YD. Effect of Cumulative Case Volume on Procedural and Clinical Outcomes in Endovascular Thrombectomy. Stroke. 2019;50(5):1178-1183.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”
hidden

Heart Attack and Stroke: Same Disease, Different Organs?

John Chen, MD

I’m spending the last month of internal medicine residency on a neurology rotation.  I suppose that’s fair; my wife, a neurology resident, had to do a whole year of medicine.  To me, the most interesting part of neurology is the parallel between stroke and acute myocardial infarction (AMI).  Conceptually these are two manifestations of a common underlying disease process.  Yet, there are glaring differences in their management, and I can’t help but wonder why.

For instance, neurologists and cardiologists use different protocols for anticoagulation and thrombolysis.  Tissue plasminogen activator (tPA) is a first line therapy for ischemic stroke unless there are contraindications, including recent use of anticoagulation.  Thrombolytic therapy is also used to treat STEMI when percutaneous coronary intervention (PCI) is not immediately available.  In contrast to stroke, STEMI thrombolysis calls for higher doses of tPA as well as concurrent infusion of heparin to prevent recurrent thrombosis.1  Perhaps thrombolysis after stroke is a more cautious affair due to the risk of reperfusion injury and hemorrhagic conversion.

For decades STEMI PCI has largely replaced tPA, yet endovascular therapy for stroke is a relatively recent innovation and its utility is limited to proximal large vessel occlusions.  While PCI relies on balloon expandable stents designed to prevent restenosis, stenting is perhaps a less attractive option in stroke due to the tortuous anatomy of intracranial vessels and the bleeding risk associated with dual antiplatelet therapy.2 Instead, neurologists perform mechanical thrombectomy using stent retrievers and aspiration catheters.  While routine thrombectomy during STEMI PCI is generally not beneficial,3 aspiration and rheolytic catheters can be used selectively in the event of large thrombus burden.

Finally, evidence does not support facilitated PCI (i.e. pretreatment with tPA prior to PCI).4-5  Interestingly, it is common practice among neurologists to pretreat with tPA prior to mechanical thrombectomy.  Theoretically pretreatment may facilitate clot extraction, but does this strategy outweigh the additional bleeding risk?6

Heart attack and stroke are similar diseases occurring in different organs.  With widespread adoption of mechanical thrombectomy for acute stroke, the fields of neurology and cardiology increasingly share similar practices.  Still, there are striking differences in stroke and AMI management—no doubt a constant source of cognitive dissonance as I complete my neurology rotation and start cardiology fellowship.

 

References:

  1. Kijpaisalratana N, Chutinet A, Suwanwela N. Hyperacute simultaneous cardiocerebral infarction: Rescuing the brain or the heart first? Frontiers in Neurology 2017;8:664.
  2. Gralla J, Brekenfeld C, Mordasini P, Schroth G. Mechanical thrombolysis and stenting in acute ischemic stroke. Stroke 2012;43:280-285.
  3. Jolly SS, James S, Dzavik V, et al. Thrombus aspiration in ST-segment elevation myocardial infarction. An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration. Circulation. 2016;135:143–152.
  4. The ASSENT-4 PCI Investigators. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI). Lancet. 2006;367:569–578.
  5. Ellis SG, Tendera M, de Belder MA, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. 2008;358:2205–17.
  6. Kasemacher J, Mordasini P, Arnold M, 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.
hidden

Referral Letter

Mirvat Alasnag, MD

A typical referral letter arrives in my tray:

A 55-year-old diabetic female noticed pain and discoloration of the right foot for several days.

 

Immediate admission was arranged for this patient:

A junior resident presents the case. She has clerked the patient and filled all the necessary forms and ticked all the necessary boxes. Everything is dated and signed appropriately. Her ankle brachial index is 0.7 on the right and 1.1 on the left. The patient falls in a Rutherford Class IV. With such thorough documentation, we were ready to pay the patient a visit and consent her for the planned peripheral angiogram and revascularization. This resident rounds with me every day and has clearly understood the process of consenting: procedural steps and complications included. I told my resident that I appreciate her energy and proactivity. I was so proud of her and thought “Hmm very little left for me to teach this young lady”. So, we walked over to the patient’s room to meet her and her family.

 

We enter the patient’s room:

My resident starts introducing the patient to me and recapping her history. In the meantime, I look at my patient from a distance. I immediately notice the anxious look. Perhaps she’s nervous about her foot and a possible amputation. I also notice how thin she is. Something doesn’t add up.  Diabetes is on the rise worldwide. Most of our poorly controlled diabetics who present with peripheral vascular disease have other end organ damage like some nephropathy or retinopathy. Most are overweight. She has none. I flip the chart in my hand and notice that her HbA1C is 7%. I ask about her weight loss. “It’s all very recent”, she says. I ask about other constitutional signs and she states there are none. She also has had no history of claudication. This doesn’t sound like long standing atherosclerosis. I approached her to examine her. I held her hand for the first time to feel her pulse. Oh, the lost art of a physical examination..Why examine her when her peripheral vasculature will be defined by a CTA and all the boxes in the chart are ticked?  The answer was right there: she was in atrial fibrillation. I glance at her EKG and sure enough she is in atrial fibrillation. Her hands told me more. She was sweating and had a tremor. I knew at this point what I needed to teach my resident. Medicine is so vast and so integrated. We cannot presume cardiovascular diseases and endocrine disorders are not interrelated. After all, this patient needed an endocrinologist.

 

Later that day she was taken to the cathlab:

Her TSH was high. Her transesophageal echocardiogram confirmed a left atrial thrombus. We discussed acute limb ischemia with the endocrinologist. We administered B blockers and obtained a consent for the procedure. Her angiogram revealed a thrombus at the right tibioperoneal trunk. Instead of whipping out the QuickCross microcatheter and GlideAdvantage wire, I performed manual aspiration of the thrombus. Fortunately, flow was restored almost immediately. The Society for Vascular Surgery and the North American Chapter of the International Society of Cardiovascular Surgery created a classification that ranged from non-threatened extremity, threatened extremity to finally ischemia with no possible salvage in 2002. Timely intervention is warranted in salvageable cases. Fogarty established surgical thromboembolectomy as the standard of care in the 1960s. Dotter introduced thrombolysis in the 1970s which evolved to current day catheter directed thrombolysis and aspiration. Both surgical and catheter directed thrombectomy have been studied. Theodoridis et al published a review article that indicated the technical success rate of endovascular techniques reaches 79.3%. A second procedure was required in 77.8% of those enrolled. The overall complication rate was 28.7%. Novel techniques that combine catheter directed low dose thrombolysis with and without mechanical thrombectomy have also been evaluated and found to be largely comparable.1-3 Procedural questions related to my patient were confined to the following:

  1. Use of a distal protection device: Trials have demonstrated a wide variation in the rate of distal embolization. This wide range is explained by the different lesion types, lengths, treatment modalities. The highest rate is in those with TASC C and D lesions, acute and subacute presentations, and with the use of atherectomy devices.4-10 However, major adverse events and amputations rates have not been significantly reduced with the use of distal protection devices.
  2. Use of an infusion catheter is usually reserved for cases where adequate flow and removal of thrombus is inadequate.

 

Upon returning to her room, there was more to discuss:

Her thyrotoxicosis was under investigation and control. Her atrial fibrillation needed to be addressed at this point. She needed rate control until she becomes euthyroid. With a thrombus in her left atrium and embolization to her lower extremity, she needed anticoagulation. The choice of an agent is another lesson for another day.

The resident and I walked out of her room with a sense of satisfaction. Both of us learned something that day. A patient is more than a referral letter..much more.

 

REFERENCES:

  1. Shrikhande GV, Khan SZ, Hussain HG, et al. Lesion types and device characteristics that predict distal embolization during percutaneous lower extremity interventions. J Vasc Surg2011;53(2):347–52.
  2. Shammas NW, Shammas GA, Dippel EJ, et al. Predictors of distal embolization in peripheral percutaneous interventions: a report from a large peripheral vascular registry. J Invasive Cardiol2009;21(12):628–31.
  3. Mendes BC, Oderich GS, Fleming MD, et al. Clinical significance of embolic events in patients undergoing endovascular femoropopliteal interventions with or without embolic protection devices. J Vasc Surg2014;59(2):359–67.e1.PMCID: PMC4492297
  4. Shammas NW, Coiner D, Shammas GA, et al. Distal embolic event protection using excimer laser ablation in peripheral vascular interventions: results of the DEEP EMBOLI registry. J Endovasc Ther2009;16(2):197–202.
  5. Karnabatidis D, Katsanos K, Kagadis GC, et al. Distal embolism during percutaneous revascularization of infra-aortic arterial occlusive disease: an underestimated phenomenon. J Endovasc Ther2006;13(3):269–80.
  6. Shammas NW, Dippel EJ, Coiner D, et al. Preventing lower extremity distal embolization using embolic filter protection: results of the PROTECT registry. J Endovasc Ther 2008;15(3):270–6.
  1. Rheolytic Pharmacomechanical Thrombectomy for the Management of Acute Limb Ischemia: Results From the PEARL Registry. Leung DA, et al. J Endovasc Ther. 2015
  2. Acute on chronic limb ischemia: From surgical embolectomy and thrombolysis to endovascular options. de Donato G, et al. Semin Vasc Surg. 2018
  3. Thrombolysis in Acute Lower Limb Ischemia: Review of the Current Literature. Theodoridis PG, et al. Ann Vasc Surg. 2018.
  4. Comparison of Low-Dose Catheter-Directed Thrombolysis with and without Pharmacomechanical Thrombectomy for Acute Lower Extremity Ischemia. Gandhi SS, et al. Ann Vasc Surg. 2018.

 
hidden

Tenecteplase: Is It Ready for Primetime?

Siddharth Sehgal, MD

In 1996, intravenous alteplase was approved by the FDA for treatment of acute ischemic stroke within 3 hours of time of onset of symptoms. Since then it remains the only drug approved for treatment of acute ischemic stroke. Subsequent clinical trial showed benefit of alteplase unto 4.5 hours from onset of symptoms.

Over the past few years, several trials have studied medications including anticoagulants and thrombolytics, but have not shown positive results. Tenecteplase is a bio-engineered form of alteplase, and is approved in the U.S. for acute myocardial infarction. In 2017, results of the NOR-TEST trial were published, which compared the efficacy and safety of tenecteplase and alteplase in an open label, randomized design1. 1100 patients were randomized 1:1 to receive either alteplase 0.9 mg/kg (max dose 90 mg) or tenecteplase 0.4 mg/kg (max dose 40 mg).  Most patients enrolled in this study had a mild stroke with median NIH stroke scale of 4. The primary outcome measure of 3 months modified rankin score 0-1 was achieved in 64% of the tenecteplase group and 63% of the alteplase group. The mortality rates and serious adverse event rates were also similar in the two treatment arms. In conclusion, this study showed that tenecteplase had similar safety and efficacy as compared to alteplase when administered to acute ischemic stroke patients within 4.5 hours of symptoms onset.

A subsequent subset analysis of patients presenting within 3 to 4.5 hours time window also had similar results in the two treatment groups, with rates of good functional outcomes and adverse events including mortality2.

In the last few years, several clinical trials have established efficacy and safety of mechanical thrombectomy for treatment of ischemic stroke caused by acute occlusion of an intracranial internal carotid artery or middle cerebral artery. The American Heart Association/Stroke Association guidelines recommend treatment with intravenous alteplase in eligible patients ,prior to mechanical thrombectomy. The EXTEND-IA TNK trial3 studied the efficacy of tenecteplase 0.25 mg/kg (max dose 25 mg) compared to alteplase 0.9 mg/kg (max dose 90 mg) in patients who subsequently underwent mechanical thrombectomy fo an intracranial large vessel occlusion. The thrombolytic drugs were administered within 4.5 hours from symptom onset. The trial was designed as a non inferiority study but showed tenecteplase to be superior than alteplase. The primary outcome of greater than 50% reperfusion of the occluded artery at the time of initial angiogram was achieved in 10% of the alteplase group and 22% in the tenecteplase group (P= 0.03 for superiority and P=0.02 for non inferiority). Moreover, tenecteplase resulted in better functional outcomes measured by median modified rankin scores at 90 days ( 2 vs 3, P=0.04). Both the treatment groups had similar rates of symptomatic intracerebral hemorrhage.

Tenecteplase has better fibrin specificity and a longer half life than alteplase. Tenecteplase can be administered as a bolus over a few seconds while alteplase requires a one hour infusion. A significant proportion of large vessel occlusion stroke patients receive intravenous thrombolysis at the initial hospital and then get transferred to a larger stroke center for mechanical thrombectomy; this is referred to as the drip and ship approach. The one hour infusion is usually initiated at the first emergency department and continued en route to the thrombectomy center. This approach can pose logistical challenges and cause treatment delays, which can be overcome if a thrombolytic can be rapidly administered as a bolus prior to patient getting transferred.

These results have now shown that tenecteplase is a promising alternative to the current standard of care thrombolysis with alteplase when treating acute ischemic stroke. This may be especially favorable for the patients who also require mechanical thrombectomy of an intracranial large vessel occlusion.

Further research is needed to establish the efficacy and obtain regulatory approval for tenecteplase in treatment of acute ischemic stroke. ATTEST-2 is an ongoing trial studying the efficacy of tenecteplase in ischemic stroke not caused by a large vessel occlusion. EXTEND-IA TNK-2 is going to compare two doses of the tenecteplase (0.25 mg/kg and 0.40 mg/kg) for safety and efficacy.  It is exciting to think that we may be getting close to the first new drug approved for treatment of acute ischemic stroke in more than 20 years.

References

  1. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017 Oct;16(10):781-788.
  2. Tenecteplase Versus Alteplase Between 3 and 4.5 Hours in Low National Institutes of Health Stroke Scale. Stroke. 2019;0
  3. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582

 
hidden

How Far Can We Go in the Early Management of Acute Ischemic Stroke?

Reem Waziry, MD, MPH, PhD

(In anticipation of the International Stroke Conference 2019 – ISC19)

Not so long ago, the benefit of endovascular thrombectomy beyond six hours of ischemic stroke onset was uncertain, particularly among patients with ischemic brain tissue that has not yet undergone infarction. The volume of irreversibly injured ischemic tissue and the volume of brain tissue that is ischemic, but not yet infarcted, could be assessed by computed tomographic perfusion imaging or a combination of diffusion and perfusion magnetic resonance imaging.1,2

Early last year, the DAWN3 and DEFUSE 34 trials’ investigators presented findings at ISC18 that lead to immediate change in the guidelines5 with substantial implications for prevention of functional dependence among stroke survivors.

The DAWN trial was a multicentre, prospective, randomized, open labelled trial conducted at 26 centers in the United States, Canada, Europe and Australia, with at least 40 mechanical thrombectomy procedures performed annually. Patients were enrolled if they were last known to be well within 6 to 24 hours earlier and had occlusion of the intracranial internal carotid artery or proximal middle cerebral artery with a mismatch between the severity of clinical deficit and the infarct volume. The mismatch criteria were defined according to age, stroke severity, occlusion site, time to treatment and type of stroke onset. Primary end points included mean score for disability and functional independence at 90 days.

The mean score on the utility-weight modified Rankin scale and rate of functional independence at 90 days were 5.5 and 49% in the thrombectomy group, compared to 3.4 and 13% in the control group. The rate of symptomatic intracranial haemorrhage and death at 90 days did not differ between the two groups.

The DEFUSE 3 trial was a multicentre, randomized, open labelled trial that included 38 centers in the United States. Patients were enrolled if they were last known to be well within 6 to 16 hours and had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral artery or internal carotid artery occlusion, an initial infarct size of less than 70ml and ratio of ischemic tissue to infarct volume of 1.8 or more were randomly assigned to thrombectomy plus standard medical therapy or standard medical therapy alone. The primary outcome was the ordinal score on the modified Rankin scale at 90 days.

The 90-days mortality rate was 14% in the endovascular therapy group compared to 26% in the medical therapy group. The absolute difference in functional independence between groups was 28% points, indicating a better 90 day functional outcomes compared to patients who had standard medical therapy alone. This mainly applies to patients who had evidence of salvageable tissue determined on the basis of a formula that incorporates early infarct size and the volume of hypoperfused tissue on perfusion imaging.

The incidence of symptomatic cerebral haemorrhage was not statistically different, yet numerically higher in the endovascular compared to the medical therapy group. Mortality was numerically lower in the endovascular therapy group. In between group differences of 24-hour infarct volume and growth after thrombectomy were not significant. Further, patients treated within six hours after stroke onset had favourable outcomes compared to other trials. This difference could be attributed to the favourable collateral circulation and slower infarct growth in patients recruited in the DEFUSE 3 trial.

Enrollment in the DAWN trial was stopped at 31 months, because the results of an interim analysis met the prespecified criterion for trial discontinuation, which was a predictive probability of superiority of thrombectomy of at least 95% for the first primary end point. Similarly, the DEFUSE 3 trial was terminated early for efficacy after 182 patients had undergone randomization, given the interim analysis results exceeded the prespecified efficacy boundary (P<0.0025). Both the DAWN and DEFUSE 3 trials used the same automated perfusion software (RAPID) to measure the volume of early infarct and hypoperfused volume.

Further advancements are anticipated at ISC19, with key questions on benefits beyond those time points and among the broader population of ischemic stroke survivors.

 

REFERENCES

  1. Albers GW, Goyal M, Jahan R, et al. Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME. Ann Neurol 2016. 79: 76-89.
  2. Wheeler HM, Mlynash M, Inoue M, et al. Early diffusion-weighted imaging and perfusion-weighted imaging lesion volumes forecast final infarct size in DEFUSE2. Stroke 2013. 44: 681
  3. Nogueira, Raul G., et al. “Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct.” New England Journal of Medicine 2018. 378:11-21.
  4. Albers, Gregory W., et al. “Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging.” New England Journal of Medicine 378: 708-718.
  5. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018. 39:46-99.

 

 
hidden

Stroke Systems Science: Travel Delays and Access to Care

Neal Parikh, MD

Advances in science cannot overcome traffic. Patients with strokes due to large vessel occlusions must be taken to hospitals that perform endovascular thrombectomy. Otherwise, these patients do not benefit from the latest and greatest in stroke neurology.

Investigators, including me, have taken interest in measuring the impact of travel delays on stroke care. With my co-investigators, a colleague and I performed a Monte Carlo simulation to model the effects of stroke transfer system configuration on endovascular therapy eligibility and expected outcomes.1 In a recent issue of Stroke, Dr. Regenhardt and colleagues present their analysis of a single hub and spoke system.2

They analyzed 234 patients who were transferred for endovascular therapy. Of these patients, who had a median ASPECTS score of 10 prior to transfer, only 27% of patients ultimately received endovascular therapy.  A median ASPECTS score of 10 correlates with very high eligibility for endovascular therapy prior to transfer.

They found, not surprisingly, that longer transfer time was associated with a decreased odds of undergoing endovascular therapy. The probability of getting endovascular therapy decreased by 1% for each additional minute of transfer time beyond 60 minutes. Being transferred at night was associated with slower transfers (despite less traffic!) and less endovascular therapy.

What does this mean? This means that a patient with a severe stroke who has the misfortune of being taken to a hospital that does not offer endovascular therapy has only a 27% probability of getting this therapy after transfer. At night time, it’s even worse.

Wonderful outcomes can be seen in clinical trials, but they do not benefit society if systems science does not keep up. Infrastructure upgrades and protocol developments may help, along with monitoring and benchmarking of transfer metrics.

References

  1. Parikh, Chatterjee, Diaz, et al. Modeling the Impact of Interhospital Transfer Network Design on Stroke Outcomes in a Large City. Stroke. 2018;49:370-376.
  2. Regenhardt, Mecca, Flavin, et al. Delays in Air or Ground Transfer of Patients for Endovascular Therapy. Stroke. 2018;49:1419-1425.

Neal Parikh Headshot

Neal S. Parikh, MD, earned his MD from Weill Cornell Medical College and completed residency training in neurology at the same institution. He is now an NIH T32 neuro-epidemiology and vascular neurology fellow at New York-Presbyterian Hospital/Columbia University Medical Center. He tweets @NealSParikhMD and contributes to Blogging Stroke as a blogger.
hidden

A different kind of extended window for stroke treatment

Neal Parikh, MD

To fanfare at International Stroke Conference 2018, the results of the DEFUSE 31 extended window thrombectomy study were announced. The American Heart Association/American Stroke Association acute ischemic stroke guidelines were immediately updated to reflect the practice-changing findings. 

A few months later, Lee Schwamm and colleagues published their findings from MR WITNESS.2 In this study, patients with unwitnessed stroke onset between 4.5 and 24 hours underwent advanced magnetic resonance imaging to identify those individuals with radiographic evidence of hyperacute stroke. Based on prior work, it was known that evolution of imaging characteristic with respect to the fluid-attenuated inversion recovery (FLAIR) sequence correlates with time from onset. Patients who met imaging criteria based on the mismatch between FLAIR signal change and diffusion restriction were given tPA.

The researchers enrolled 80 individuals at multiple centers. Patients were treated at a median of 11 hours from their last known well. The rates of adverse events were very low and within the range of adverse event rates observed in prior stroke treatment trials. 

The standard stroke treatment paradigm allows patients to be treated within 4.5 hours of symptom onset. In general, patients treated beyond this window are at greater risk of brain hemorrhage and poor outcomes. The results of this Phase 2a study challenge the 4.5 hour time window. Like DEFUSE 3, this study uses advanced imaging to personalize acute stroke treatment. A frequent reason for patients to not receive tPA for stroke treatment has been that patients often present to hospitals too late. Expanding the time window for non-large vessel occlusion strokes, which are the vast majority of strokes but nonetheless disabling, has great public health implications. With the rest of the stroke community, I look forward to results of an efficacy trial.

References

  1. Albers GW, Marks MP, Kemp SK, Christensen S, Tsai JP, Santiago O, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. NEJM 2018; 378:708-718.
  2. Schwamm LH, Wu O, Song SS, Ford AL, Hsia AW, Muzikansky A, Betensky RA, et al. Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results. Ann Neurol 2018 Apr 24 [Epub ahead of print].

Neal Parikh Headshot

Neal S. Parikh, MD, earned his MD from Weill Cornell Medical College and completed residency training in neurology at the same institution. He is now an NIH T32 neuro-epidemiology and vascular neurology fellow at New York-Presbyterian Hospital/Columbia University Medical Center. He tweets @NealSParikhMD and contributes to Blogging Stroke as a blogger.
hidden

Promising Advance In Stroke Thrombolysis Research: Tenecteplase

Neal Parikh, MD

A recent New York Times article re-surfaced the ‘debate’ regarding alteplase (IV-tPA) for ischemic stroke.1 There are some who continue to argue that the data for IV-tPA are not convincing. In this context, and otherwise, it is worthwhile to discuss a recent study comparing tenecteplase versus alteplase among patients with large vessel occlusion.2

In this study, 202 patients presenting within the IV-tPA treatment window of 4.5 hours and with an ischemic stroke due to large vessel occlusion were randomized to receive IV-tPA versus IV-tenecteplase prior to proceeding with mechanical thrombectomy. The main outcomes relevant for this discussion are the primary outcome of substantial reperfusion (restoration of blood flow in the affected area) and the safety outcome of brain hemorrhage.

Whereas 10% of patients who had received IV-tPA achieved substantial reperfusion prior to undergoing mechanical thrombectomy, 22% achieved substantial reperfusion in the tenecteplase group. The number of brain hemorrhages was the same in both groups (5-6%).

If confirmed, this represents a tremendous advance in thrombolysis because many patients require lengthy transport to reach a center where thrombectomy can be performed. Achieving reperfusion without increased risk of hemorrhage, potentially in the field using stroke ambulances and telemedicine, could dramatically improve population-level care for this otherwise very disabling form of stroke.

Further, these data suggest support the stability of the 6% estimate of brain hemorrhage risk with IV-thrombolysis. The observation that the hemorrhage risk (5 vs 6%) was the same regardless of reperfusion rate (10 vs 22%) is intriguing – if the two are independent, is the risk of hemorrhage from thrombolysis from something other than reperfusion? Further, the results of this study will spur additional study and we will thus have contemporary, high-quality data regarding the efficacy and safety of thrombolysis.

References

  1. https://www.nytimes.com/2018/03/26/health/stroke-clot-buster
  2. Campbell, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. NEJM. 2018:378:1573-82.

Neal Parikh Headshot

Neal S. Parikh, MD, earned his MD from Weill Cornell Medical College and completed residency training in neurology at the same institution. He is now an NIH T32 neuro-epidemiology and vascular neurology fellow at New York-Presbyterian Hospital/Columbia University Medical Center. He tweets @NealSParikhMD and contributes to Blogging Stroke as a blogger.