Update: What are Major Pharmacotherapy Updates from the 2026 AHA/ASA Stroke Guidelines?

Background
The result of an occlusion in the cerebral vascular supply that results in tissue hypoxia and damage, acute ischemic stroke (AIS) affects more than 690,000 people annually in the United States.^1,2 Stroke is also currently the number 4 cause of death in the US, resulting in more than 165,000 deaths per year. In order to minimize neurologic injury and reduce mortality and long-term disability and complications, administration of intravenous thrombolytics (IVT) is the mainstay of acute pharmacologic therapy used to improve functional outcomes; however, thrombolytic use is associated with a risk of bleeding and serious bleeding events such as intracranial hemorrhage (ICH).¹ In January 2026, the American Heart Association (AHA) and American Stroke Association (ASA) published updated guidelines addressing the early management of AIS,³ which replace the 2018 guidelines and their 2019 update.^4,5

Choice of Thrombolytic Agent
In adult patients with AIS who present within 4.5 hours of symptom onset or their last known well and are eligible for IVT, the 2026 guidelines endorse the use of tenecteplase or alteplase in order to improve functional outcomes.³ This differs from the prior guideline that primarily endorsed the use of alteplase for AIS and suggested tenecteplase as an alternative agent.^3,5 The 2026 guideline states that tenecteplase may offer practical advantages over alteplase due to a single bolus and fewer dosing complexities.³ For AIS, a dose of 0.25 mg/kg (up to a maximum of 25 mg) of tenecteplase intravenous (IV) push or 0.9 mg/kg (up to a maximum of 90 mg) of alteplase, 10% administered as a bolus, and the remainder infused over 60 minutes, is recommended. Multiple large, randomized trials support the safety and efficacy of a 0.25 mg/kg dose of tenecteplase instead of a higher dose of 0.4 mg/kg,^6-10 as several studies have demonstrated no advantages with higher dosing and an increased risk of symptomatic intracerebral hemorrhage (sICH).^11-14

Extended Window for IV Thrombolysis
The updated 2026 guideline has extended the time window for IVT in select patients.³ Treatment with IVT in patients within AIS within 4.5 hours of symptom onset has been well-established as the standard of care;³ however, the EXTEND and TRACE-3 trials since the last guideline demonstrated additional benefit during an extended time period in patients that met certain computed tomography (CT) parameters.^3,15,16 The guideline indicates that IVT may be reasonable to administer in patients with AIS and salvageable ischemic penumbra identified on advanced imaging who either awaken with stroke symptoms within 9 hours from the midpoint of sleep or are 4.5 to 9 hours from their last known well.³ Additionally, in patients with AIS due to large vessel occlusion (LVO) and salvageable ischemic penumbra presenting within 4.5 to 24 hours after their last known well who cannot receive endovascular thrombectomy (EVT), IVT may be beneficial.

In the TRACE-3 trial, among those with salvageable brain tissue who received alteplase between 4.5 and 9 hours after stroke onset or awakening with stroke symptoms, there was a greater proportion of patients with minor or no neurologic deficits compared to those who received placebo.¹⁵ In the EXTEND trial, patients with AIS due to LVO who did not undergo EVT that received tenecteplase 4.5 to 24 hours after stroke onset had less disability and similar survival compared to patients that received antiplatelet therapy, although the rate of intracranial hemorrhage was higher.¹⁶

Glycemic Management
In patients with AIS and persistent hyperglycemia, the guidelines indicate a blood glucose range of 140 to 180 mg/dL is still reasonable to target with close monitoring.³ The updated guideline further indicates that aggressive glucose lowering to levels of 80 to 130 mg/dL is not recommended as it does not improve clinical outcomes and increases the risk of severe hypoglycemia. In patients with AIS, glucose levels of $\lt$60 mg/dL still warrant treatment.

Blood Pressure Management
A blood pressure goal of $\lt$185/110 mm Hg is still recommended prior to initiation of IVT, with blood pressure maintained at $\lt$180/105 mmHg for the first 24 hours after IVT; however, the new guidelines additionally indicate that intensive systolic blood pressure (SBP) lowering after IVT to $\lt$140 mmHg is not recommended, as it has not been associated with improved functional outcomes.³

Pediatric Stroke Management
The 2026 guideline additionally provides new acute stroke recommendations for pediatric patients, and states that in pediatric patients 28 days to 18 years of age with confirmed AIS who present within 4.5 hours of symptom onset and disabling deficits, IVT with alteplase can be considered as the drug has determined to be safe; however, efficacy is unclear.³ The safety of alteplase is supported by the pediatric TIPS trial, which was stopped due to a lack of patient recruitment.³ The study found that administration of IV alteplase 0.9 mg/kg within 0 to 4.5 hours after symptom onset to patients with a Pediatric National Institutes of Health Stroke Scale (PedNIHSS) ≥4 was safe,^3,17 with the risk of sICH low in appropriately selected patients.¹⁷

Conclusion
The 2026 AHA/ASA stroke guidelines provide several major updates to AIS management. New and impactful recommendations include the endorsement of tenecteplase as treatment for IVT, an extended-time frame for IV thrombolysis in patients with salvageable brain tissue identified on advanced imaging, and specific pediatric stroke management recommendations. The guideline also endorses the use of less aggressive glycemic management in patients with persistent hyperglycemia and less intensive blood pressure lowering in patients after IVT.

References

1. Melissa N, Rachael S. Stroke. In: Haines ST, Nolin TD, Ellingrod VL, Posey L, Cocohoba J, Holle L. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 13th Edition. McGraw Hill; 2026. Accessed March 21, 2026. https://accesspharmacy-mhmedical-com.proxy.cc.uic.edu/content.aspx?bookid=3386§ionid=292508297.

2. American Stroke Association. Acute Ischemic Stroke Infographic. Accessed March 21, 2026. https://www.stroke.org/en/about-stroke/types-of-stroke/ischemic-stroke-clots/ais-infographic.

3. Prabhakaran S, Gonzalez NR, Zachrison KS, et al. 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. Published online January 26, 2026. doi:10.1161/STR.0000000000000513.

4. Powers WJ, Rabinstein AA, Ackerson T, 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(3):e46-e110. doi:10.1161/STR.0000000000000158.

5. Powers WJ, Rabinstein AA, Ackerson T, 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(12):e344-e418. doi:10.1161/STR.0000000000000211.

6. Muir KW, Ford GA, Ford I, et al. Tenecteplase versus alteplase for acute stroke within 4·5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial. Lancet Neurol. 2024;23(11):1087-1096. doi:10.1016/S1474-4422(24)00377-6.

7. Menon BK, Buck BH, Singh N, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022;400(10347):161-169. doi:10.1016/S0140-6736(22)01054-6.

8. Wang Y, Li S, Pan Y, Li H, Parsons MW, Campbell BCV, Schwamm LH, Fisher M, Che F, Dai H, et al; TRACE-2 Investigators. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial. Lancet. 2023;401:645–654. doi: 10.1016/S0140-6736(22)02600-9.

9. Parsons MW, Yogendrakumar V, Churilov L, , et al; TASTE investigators. Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4.5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial. Lancet Neurol. 2024;23:775–786. doi: 10.1016/S1474-4422(24)00206-0.

10. Meng X, Li S, Dai H, et al. Tenecteplase vs alteplase for patients with acute ischemic stroke: the ORIGINAL randomized clinical trial. JAMA. 2024;332:1437–1445. doi:10.1001/jama.2024.14721.

11. Kvistad CE, Næss H, Helleberg BH, et al. Tenecteplase versus alteplase for the management of acute ischaemic stroke in Norway (NOR-TEST 2, part A): a phase 3, randomised, open-label, blinded endpoint, non-inferiority trial. Lancet Neurol. 2022;21(6):511-519. doi:10.1016/S1474-4422(22)00124-7.

12. Haley EC Jr, Thompson JL, Grotta JC, et al. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke. 2010;41(4):707-711. doi:10.1161/STROKEAHA.109.572040.

13. Logallo N, Novotny V, Assmus J, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017;16(10):781-788. doi:10.1016/S1474-4422(17)30253-3.

14. Campbell BCV, Mitchell PJ, Churilov L, et al. Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial. JAMA. 2020;323(13):1257-1265. doi:10.1001/jama.2020.1511.

15. Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019;380(19):1795-1803. doi:10.1056/NEJMoa1813046.

16. Xiong Y, Campbell BCV, Schwamm LH, et al. Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy. N Engl J Med. 2024;391(3):203-212. doi:10.1056/NEJMoa2402980.

17. Amlie-Lefond C, Shaw DWW, Cooper A, et al. Risk of Intracranial Hemorrhage Following Intravenous tPA (Tissue-Type Plasminogen Activator) for Acute Stroke Is Low in Children. Stroke. 2020;51(2):542-548. doi:10.1161/STROKEAHA.119.027225.

Prepared by:
Christie Denton, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

April 2026

The information presented is current as of March 21, 2026. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.