Parneet Grewal, MD

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.

The evidence-based treatment of acute ischemic stroke (AIS) is constantly changing with new high-quality evidence, and the American Heart Association (AHA) has provided focused updates and guidelines on specific topics relating to the management of patients with AIS since 2013. The 2018 AIS Guidelines were published online on January 24, 2018 and are being followed throughout the United States for patient management.1 An independent evidence review committee appointed by the AHA Stroke Council’s Scientific Statements Oversight Committee performed a systemic review of literature, and a 2019 update to the 2018 guidelines was prepared with some new or revised recommendations. The guidelines focus on the prehospital care, emergency evaluation and treatment with intravenous alteplase (IV-tPA) and intra-arterial therapies and in hospital-management. In this blog post, I will discuss some of the recommendations that are new since the 2018 guidelines.

As per the updated guidelines, the benefit of bypassing the closest hospital capable of giving IV-tPA in favor of stroke centers providing a higher level of care including endovascular treatment (EVT) is uncertain at this point (COR: IIb, LOE: B-NR);2 however, the AHA does recommend that prehospital procedures to identify patients ineligible for IV-tPA and having a likelihood of large vessel occlusion (LVO) should be developed so that rapid transport of patients to centers capable of EVT could be facilitated (COR: IIb, LOE: C-EO).3,4 Transportation of patients with a stroke due to an LVO rapidly to improves the probability of effective reperfusion for those who qualify for this approach.5 However, the sensitivities and specificities of currently used LVO scales range from 47% to 73% and from 78% to 90%, respectively. A meta-analysis by the 2018 AHA systemic review committee concluded that, “No scale predicted LVO with both high sensitivity and high specificity,” which necessitates the development of new prehospital procedures.6

The guidelines support alteplase decision-making via telephone consultation to community physicians in absence of an in-person stroke team and telestroke system (COR: IIb, LOE: C-LD).7 Another important update to the 2018 guidelines is the recommendation that IV-tPA could be beneficial in patients with AIS who wake up with stroke symptoms or have unclear time of onset > 4.5 hours from last known normal (LKN). This is based on the WAKE-UP trial, which showed benefit in this patient population if they have MRI mismatch between abnormal signal on DW-MRI and no visible signal on FLAIR (COR: IIb, LOE: B-R). The eligibility criteria for this trial included patients who were 18-80 years of age, had DW-MRI lesion < 1/3 of middle cerebral artery territory, National Institute of Health Stroke Scale (NIHSS) < 25 and were not candidates for EVT.8 This recommendation will lead to major restructuring of hospital emergency department stroke alert protocols to incorporate early MRI access for this patient population. The role of emergency medical services (EMS) transport and primary stroke centers without MRI capability is yet to be determined in this patient subset. Also, per the AHA, IV-tPA is not recommended for patients with mild non-disabling symptoms with NIHSS 0-5 who are otherwise candidates for the therapy and present within 3 or 3-4.5 hours of LKN (COR: III No Benefit, LOE: R and LD).9-16 Acute neurological deficits judged to not interfere with activities of daily living or prevent return to work are patient specific, and additional factors should be considered when making individual patient care decisions. There has been a recent focus on tenecteplase as an alternative IV- fibrinolytic agent due to it higher affinity binding to fibrin, greater resistance to inactivation by plasminogen activator inhibitor-1(PAI-1), less disruption of hemostasis and longer free plasma half-life (2hr vs 1 hr) allowing single IV bolus administration. Per the 2019 AHA guideline update, IV-tenecteplase (single IV bolus of 0.25-mg/kg, maximum 25 mg) could be used for patients without contraindications to thrombolysis who are also eligible to undergo EVT (COR: IIb, LOE: B-R).17

The AHA committee also discussed reasonable use of resources, including MRI, intracranial vessel imaging, cardiac monitoring and echocardiography, in these guidelines. They also urged providers to discuss care options and all possible outcomes with patients and family as soon as possible in brain swelling and take patient preferences in decision making when considering interventions so that interventions that are not helpful or may not align with the patient’s wishes along with caregiver bereavement and distress could be avoided (COR: I, LOE: C-EO).18

These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke and will not be applicable to all patients. Local resources and expertise, specific clinical circumstances and patient preferences, and evidence published since the issuance of these guidelines should be considered when making individual patient care decisions.


1. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 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;49:e46-e110.

2. American Heart Association. Severity-based stroke triage algorithm for EMS. Accessed December 1, 2017.       

3. Saver JL, Fonarow GC, Smith EE, Reeves MJ, Grau-Sepulveda MV, Pan W, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA. 2013;309:2480–2488.

4. Saver JL, Goyal M, van der Lugt A, Menon BK, Majoie CB, Dippel DW, et al; HERMES Collaborators. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316:1279–1288.

5. Bourcier R, Goyal M, Liebeskind DS, Muir KW, Desal H, Siddiqui AH, et al. Association of time from stroke onset to groin puncture with quality of reperfusion after mechanical thrombectomy: A meta-analysis of individual patient data from 7 randomized clinical trials. JAMA Neurol. 2019.

6. Smith EE, Kent DM, Bulsara KR, Leung LY, Lichtman JH, Reeves MJ, et al. Accuracy of prediction instruments for diagnosing large vessel occlusion in individuals with suspected stroke: A systematic review for the 2018 guidelines for the early management of patients with acute ischemic stroke. Stroke. 2018;49:e111-e122.

7. Fong WC, Ismail M, Lo JW, Li JT, Wong AH, Ng YW, et al. Telephone and teleradiology guided thrombolysis can achieve similar outcome as thrombolysis by neurologist on-site. J Stroke Cerebrovasc Dis. 2015;24:1223–1228.

8. Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, et al; WAKE-UP Investigators. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379:611–622.

9. Khatri P, Tayama D, Cohen G, Lindley RI, Wardlaw JM, Yeatts SD, et al; PRISMS and IST-3 Collaborative Groups. Effect of intravenous recombinant tissue-type plasminogen activator in patients with mild stroke in the Third International Stroke Trial-3: post hoc analysis. Stroke. 2015;46:2325–2327.

10. National Institute of  Neurological Disorders Stroke rtPA Stroke Study Group. Recombinant tissue plasminogen activator for minor strokes: the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study experience. Ann Emerg Med. 2005;46:243–252.

11. Ingall TJ, O’Fallon WM, Asplund K, Goldfrank LR, Hertzberg VS, Louis TA, et al. Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial. Stroke. 2004;35:2418–2424.

12. Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, et al; Stroke on Thrombolysis Trialists’ Collaborative Group. Effect of treatment delay, age, and stroke severity the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384:1929–1935.

13. Bluhmki E, Chamorro A, Dávalos A, Machnig T, Sauce C, Wahlgren N, et al. Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke (ECASS III): additional outcomes and subgroup analysis of a randomised controlled trial. Lancet Neurol. 2009;8:1095–1102.

14. Ahmed N, Wahlgren N, Grond M, Hennerici M, Lees KR, Mikulik R, et al; SITS Investigators. Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR. Lancet Neurol. 2010;9:866–874.

15. Romano JG, Smith EE, Liang L, Gardener H, Camp S, Shuey L, et al. Outcomes in mild acute ischemic stroke treated with intravenous thrombolysis: a retrospective analysis of the Get With the Guidelines-Stroke registry. JAMA Neurol. 2015;72:423–431.

 16. Khatri P, Kleindorfer DO, Devlin T, Sawyer RN Jr, Starr M, Mejilla J, et al; PRISMS Investigators. 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.

17. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al; EXTEND-IA TNK Investigators. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378:1573–1582.

18. Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A, et al; DECIMAL, DESTINY, and HAMLET Investigators. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007;6:215–222.