In 2021, there were 7.3 million deaths from stroke worldwide.[16]GBD 2021 Stroke Risk Factor Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024 Oct;23(10):973-1003.
https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00369-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39304265?tool=bestpractice.com
Stroke is a leading cause of serious long-term disability in the US and worldwide.[16]GBD 2021 Stroke Risk Factor Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024 Oct;23(10):973-1003.
https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00369-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39304265?tool=bestpractice.com
[199]Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics - 2021 update: a report from the American Heart Association. Circulation. 2021 Feb 23;143(8):e254-e743.
https://www.doi.org/10.1161/CIR.0000000000000950
http://www.ncbi.nlm.nih.gov/pubmed/33501848?tool=bestpractice.com
Prognosis of functional outcome can be reliably performed by well-validated prognostic scores like the ASTRAL score or the iScore.[200]Cooray C, Mazya M, Bottai M, et al. External validation of the ASTRAL and DRAGON scores for prediction of functional outcome in stroke. Stroke. 2016 Jun;47(6):1493-9.
https://www.ahajournals.org/doi/full/10.1161/strokeaha.116.012802
http://www.ncbi.nlm.nih.gov/pubmed/27174528?tool=bestpractice.com
Intravenous thrombolysis and dedicated stroke units are the only interventions shown to improve stroke outcome.
Common medical complications of stroke include aspiration pneumonia, depression, and deep vein thrombosis.
A meta-analysis study on the efficacy of physiotherapy following stroke found that a variety of interventions improved functional outcomes, even when they were applied late after stroke.[201]Ferrarello F, Baccini M, Rinaldi LA, et al. Efficacy of physiotherapy interventions late after
stroke: a meta-analysis. J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):136-43.
http://www.ncbi.nlm.nih.gov/pubmed/20826872?tool=bestpractice.com
The risk of stroke within 90 days after a first stroke is ≈5%, but the risk can vary greatly from >10% to <1%, depending in part on mechanism.[202]Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-467.
https://www.ahajournals.org/doi/10.1161/STR.0000000000000375
http://www.ncbi.nlm.nih.gov/pubmed/34024117?tool=bestpractice.com
In one registry-based study, the overall 1-year and 10-year risks of recurrence were 4% and 13% following first-time ischaemic stroke.[203]Skajaa N, Adelborg K, Horváth-Puhó E, et al. Risks of stroke recurrence and mortality after first and recurrent strokes in Denmark: a nationwide registry study. Neurology. 2022 Jan 24;98(4):e329-42.
http://www.ncbi.nlm.nih.gov/pubmed/34845054?tool=bestpractice.com
The risk of recurrence increased with age and was higher for men and following mild versus more severe stroke. For ischaemic stroke, the 1-year and 10-year risks of all-cause mortality were 17% and 56% after a first-time stroke, and 25% and 70% after a recurrent stroke.[203]Skajaa N, Adelborg K, Horváth-Puhó E, et al. Risks of stroke recurrence and mortality after first and recurrent strokes in Denmark: a nationwide registry study. Neurology. 2022 Jan 24;98(4):e329-42.
http://www.ncbi.nlm.nih.gov/pubmed/34845054?tool=bestpractice.com
The highest recurrence rate is seen in large artery atherosclerosis and cardioembolic stroke subtypes.[204]Kolmos M, Christoffersen L, Kruuse C. Recurrent ischemic stroke - a systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2021 Aug;30(8):105935.
https://www.strokejournal.org/article/S1052-3057(21)00338-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34153594?tool=bestpractice.com
Studies examining decreasing trends in stroke recurrence over 20 years suggest secondary prevention measures have been effective, and effective secondary prevention can reduce the risk of recurrent events by up to 80%.[205]Flach C, Muruet W, Wolfe CDA, et al. Risk and secondary prevention of stroke recurrence: a population-base cohort study. Stroke. 2020 Aug;51(8):2435-44.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7382537
http://www.ncbi.nlm.nih.gov/pubmed/32646337?tool=bestpractice.com
Patients with atrial fibrillation
Patients with atrial fibrillation and first ischaemic stroke remain at increased risk of recurrent ischaemic stroke and death even while taking oral anticoagulation. Recurrent ischaemic stroke (cumulative incidence at 1 year: 7.0%) and cumulative incidence of mortality at 3 months after stroke was 12.4%.[206]Benz AP, Hohnloser SH, Eikelboom JW, et al. Outcomes of patients with atrial fibrillation and ischemic stroke while on oral anticoagulation. Eur Heart J. 2023 May 21;44(20):1807-14.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10411934
http://www.ncbi.nlm.nih.gov/pubmed/37038327?tool=bestpractice.com
This may be related to causes related to atrial fibrillation (i.e., inadequate intensity of anticoagulation due to underdosing, non-compliance, failure to account for food interaction, particularly for rivaroxaban, or drug-drug interactions, inappropriate perioperative management, and cardioembolism despite anticoagulation) and causes unrelated to atrial fibrillation (i.e., stroke caused by large vessel arteriosclerosis, cerebral small vessel disease, aortic arch disease, or occult cancer).[207]Seiffge DJ, Cancelloni V, Räber L, et al. Secondary stroke prevention in people with atrial fibrillation: treatments and trials. Lancet Neurol. 2024 Apr;23(4):404-17.
https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00037-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/38508836?tool=bestpractice.com
In these patients, non-atrial fibrillation related causes should be considered along with drug-related issues (non-adherence or inadequate dosing).[207]Seiffge DJ, Cancelloni V, Räber L, et al. Secondary stroke prevention in people with atrial fibrillation: treatments and trials. Lancet Neurol. 2024 Apr;23(4):404-17.
https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00037-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/38508836?tool=bestpractice.com
Patients receiving alteplase
Patients treated with alteplase (if given within 4.5 hours of onset of symptoms) have a better functional outcome than patients not treated with alteplase. There is, however, an increased risk of intracerebral haemorrhage with alteplase; this does not seem to affect death or dependency at 3 months.[65]Wardlaw JM, Murray V, Berge E, et al. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014 Jul 29;(7):CD000213.
https://www.doi.org/10.1002/14651858.CD000213.pub3
http://www.ncbi.nlm.nih.gov/pubmed/25072528?tool=bestpractice.com
[120]Davis S, Holmes M, Simpson E, et al. Alteplase for the treatment of acute ischaemic stroke (review of technology appraisal 122): a single technology appraisal. School of Health and Related Research (ScHARR), University of Sheffield. May 2012 [internet publication].
https://www.nice.org.uk/guidance/ta264/documents/stroke-acute-ischaemic-alteplase-review-of-ta122-evidence-review-group-report2
[208]Hacke W, Lyden P, Emberson J, et al. Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: individual-patient-data meta-analysis of randomized trials. Int J Stroke. 2018 Feb;13(2):175-89.
https://www.doi.org/10.1177/1747493017744464
http://www.ncbi.nlm.nih.gov/pubmed/29171359?tool=bestpractice.com
Patients receiving tenecteplase
Tenecteplase within 4.5 hours of ischaemic stroke due to large vessel occlusion is non-inferior to alteplase in terms of excellent functional outcome (90-day modified Rankin Scale [mRS] scores of 0-1) and may be superior to alteplase in terms of good functional outcome (90-day mRS scores of 0-2), as supported by meta-analysis of several randomised controlled trials.[107]Alamowitch S, Turc G, Palaiodimou L, et al. European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke. Eur Stroke J. 2023 Mar;8(1):8-54.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069183
http://www.ncbi.nlm.nih.gov/pubmed/37021186?tool=bestpractice.com
[209]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 Oct;16(10):781-8.
http://www.ncbi.nlm.nih.gov/pubmed/28780236?tool=bestpractice.com
[210]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 Jun;21(6):511-9.
http://www.ncbi.nlm.nih.gov/pubmed/35525250?tool=bestpractice.com
[211]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 Apr;41(4):707-11.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860601
http://www.ncbi.nlm.nih.gov/pubmed/20185783?tool=bestpractice.com
[212]Wang Y, Li S, Pan Y, et al. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial. Lancet. 2023 Feb 25;401(10377):645-54.
http://www.ncbi.nlm.nih.gov/pubmed/36774935?tool=bestpractice.com
[213]Yogendrakumar V, Churilov L, Guha P, et al. Tenecteplase treatment and thrombus characteristics associated with early reperfusion: an EXTEND-IA TNK trials analysis. Stroke. 2023 Mar;54(3):706-14.
https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.122.041061
http://www.ncbi.nlm.nih.gov/pubmed/36727510?tool=bestpractice.com
[214]Warach SJ, Ranta A, Kim J, et al. Symptomatic intracranial hemorrhage with tenecteplase vs alteplase in patients with acute ischemic stroke: the comparative effectiveness of routine tenecteplase vs alteplase in acute ischemic stroke (CERTAIN) collaboration. JAMA Neurol. 2023 Jul 1;80(7):732-8.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10230371
http://www.ncbi.nlm.nih.gov/pubmed/37252708?tool=bestpractice.com
[215]Parsons MW, Yogendrakumar V, Churilov L, et al. 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 Aug;23(8):775-86.
http://www.ncbi.nlm.nih.gov/pubmed/38880118?tool=bestpractice.com
[216]Bala F, Singh N, Buck B, et al. Safety and efficacy of tenecteplase compared with alteplase in patients with large vessel occlusion stroke: a prespecified secondary analysis of the ACT randomized clinical trial. JAMA Neurol. 2023 Aug 1;80(8):824-32.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10334294
http://www.ncbi.nlm.nih.gov/pubmed/37428494?tool=bestpractice.com
Low-quality trial evidence suggests no significant differences in terms of mortality secondary to symptomatic intracerebral haemorrhage.[107]Alamowitch S, Turc G, Palaiodimou L, et al. European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke. Eur Stroke J. 2023 Mar;8(1):8-54.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069183
http://www.ncbi.nlm.nih.gov/pubmed/37021186?tool=bestpractice.com
Tenecteplase is not recommended for patients with ischaemic stroke on awakening from sleep or of unknown onset who undergo no brain imaging other than computed tomography (CT). In a phase 3 randomised controlled trial of patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days versus the control group, and there was no difference in mortality between groups.[217]Roaldsen MB, Eltoft A, Wilsgaard T, et al. Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2023 Feb;22(2):117-26.
http://www.ncbi.nlm.nih.gov/pubmed/36549308?tool=bestpractice.com