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Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). T he identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 ± 9.5 years) underwent a TTE evaluation; 63 patients (7.4 %) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3 %) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2 %) among whom 51 (9.3 %) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7 %. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95 % CI 1.06-4.29, p = 0.033) and CHA2DS2-VASc score (OR 1.22; 95 % CI 1.04-1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon.

Paciaroni et AL JON 2015

IST-3 Bibliography: published full papers in peer-reviewed journals

  1.  Innes K. Thrombolysis for acute ischaemic stroke: core nursing requirements. British Journal of Nursing 2003;12(7):416-24
  2. Kane I, Lindley R, Lewis S, Sandercock P. Impact of stroke syndrome and stroke severity on the process of consent in the Third International Stroke Trial. Cerebrovascular Diseases 2006;21:348-52

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=91541&Ausgabe=231712&ProduktNr=224153&filename=91541.pdf

  1. Whiteley W, Lindley R, Wardlaw J, Sandercock P. Third International Stroke Trial. Int J Stroke. 2006;1:172-6.

http://onlinelibrary.wiley.com/doi/10.1111/j.1747-4949.2006.00043.x/full

  1. Sandercock P, Lindley R, Wardlaw J, Protocol 06PRT/1269: Third International Stroke Trial (IST-3). Lancet

     http://www.thelancet.com/journals/lancet/misc/protocol/06PRT-1269.

  1. Wardlaw JM, Bath P, Sandercock P, Perry D, Palmer J, Watson G, Lloyd S, Geddes J, Farrall A. The NeuroGrid stroke exemplar clinical trial protocol. Int J Stroke. 2007;2:63-9 http://onlinelibrary.wiley.com/doi/10.1111/j.1747-4949.2007.00092.x/full
  2. The third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke. Sandercock P, Lindley R, Wardlaw J, Dennis M, Lewis S, Venables G, Kobayashi A, Czlonkowska A, Berge E, Bruins Slot K, Murray V, Peeters A, Hankey G, Matz K, Brainin M, Ricci S, Celani MG, Righetti E, Cantisani T, Gubitz G, Phillips S, Arauz A, Prasad K, Correia M, Lyrer P; the IST-3 collaborative group. Trials 2008;9(1):37. http://www.trialsjournal.com/content/9/1/37
  3. SCOPE (Stroke Complications and Outcomes Prediction Engine) Collaborations and IST. Predicting outcome in hyper-acute stroke: validation of a prognostic model in the Third International Stroke Trial (IST3). JNNP 2008;79:397-400

http://jnnp.bmj.com/content/79/4/397.full.pdf+html

  1. EPITHET-where next? Sandercock P, Wardlaw J, Dennis M, Lindley R, Hankey G, Matz K, Peeters A, Phillips S, Gubitz G, Prasad K, Ricci S, Celani MG, Righetti E, Cantisani T, Arauz A, Berge E, Slot KB, Kobayashi A, Czlonkowska A, Correia M, Murray V, Lyrer P, Venables G; IST-3 Collaborative Group. Lancet Neurology 2008;7(7):570-1.

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(08)70123-6/fulltext

  1. Oxfordshire community stroke project clinical stroke syndrome and appearances of tissue and vascular lesions on pre-treatment CT in hyper-acute ischemic stroke among the first 510 patients in the Third International Stroke Trial (IST-3). Kobayashi A, Wardlaw J, Lindley R, Lewis S, Sandercock P, Czlonkowska A; IST-3 Collaborative Group.Stroke 2009;40(3):743-8.

http://stroke.ahajournals.org/content/40/3/743.full

  1. Should more patients with acute ischaemic stroke receive thrombolytic treatment? Wardlaw J, Murray V, Sandercock P,BMJ 2009; 339.      http://www.bmj.com/content/339/bmj.b4584
  2. The Third International Stroke Trial: Thrombolysis (IST-3) in Poland: are we recruiting the right patients? Czlonkowska A, Kobayashi A, Lewis S, Sandercock P, Lindley R, Baranska-Gieruszczak M on behalf of the IST-3 collaborative group. Polish Journal of Neurology and Neurosurgery. 2009; 43, 3:228-235.

http://www.termedia.pl/Original-paper-The-Third-International-Stroke-Trial-Thrombolysis-IST-3-in-Poland-are-we-recruiting-the-right-patients-,15,12742,0,1.html

  1. Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited. Sandercock P, Lindley R, Wardlaw J, Dennis M, Lewis S, Venables G, Kobayashi A, Czlonkowska A, Berge E, Bruins Slot K, Murray V, Peeters A, Hankey G, Matz K, Brainin M, Ricci S, Celani MG, Righetti E, Cantisani T, Gubitz G, Phillips S, Arauz A, Prasad K, Correia M, Lyrer P; the IST-3 collaborative group. Trials2011, 12:252

http://www.trialsjournal.com/content/12/1/252

  1. How many patients might receive thrombolytic therapy in the light of the ECASS-3 and IST-3 data? Jan Bembenek, Adam Kobayashi, Peter Sandercock, Anna Czlonkowska. Int J Stroke 2010; 5:428–431.

http://onlinelibrary.wiley.com/doi/10.1111/j.1747-4949.2010.00479.x/full

  1. ‘Where are we now with intravenous thrombolysis for acute ischaemic stroke’? Peter Sandercock, Joanna Wardlaw, and Richard Lindley. Int J Stroke 2010; 5: 381–382: http://onlinelibrary.wiley.com/doi/10.1111/j.1747-4949.2010.00465.x/abstract
  2. Statistical analysis plan for the third International Stroke Trial (IST-3); part of a ‘thread’ of reports of the trial. Int J Stroke 2012; 7: 186–18. http://onlinelibrary.wiley.com/doi/10.1111/j.1747-4949.2012.00782.x/full
  3. The IST-3 Collaborative Group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet 2012; 379(9834):2352-2363.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60768-5/fulltext

  1. Wardlaw J M, Murray V, Berge E, del Z G, Sandercock P, Lindley R L et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 2012; 379(9834):2364-2372. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60738-7/fulltext
  2. IST-3 Collaborative Group. Effect of thrombolysis with alteplase within 6h of acute ischaemic stroke on long-term outcomes (the third international stroke trial [IST-3]): 18-month follow-up of a randomised controlled trial. Lancet Neurology 2013;12:768-76. doi:10.1016/S1474-4422(13)70130-3.

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(13)70130-3/fulltext

  1. Whiteley WN, Thompson D, Murray G, Cohen G, Lindley RI, Wardlaw J, Sandercock P. Targeting recombinant tissue-type plasminogen activator in acute ischemic stroke based on risk of intracranial hemorrhage or poor functional outcome. An analysis of the Third International Stroke trial. Stroke 2014;45:1000-6: http://dx.doi.org/1161/STROKEAHA.113.004362
  2. Whiteley WN, Thompson D, Murray G, Cohen G, Lindley RI, Wardlaw J et al. Effect of Alteplase Within 6 Hours of Acute Ischemic Stroke on All-Cause Mortality (Third International Stroke Trial). Stroke Published online before print November 4, 2014, http://dx.doi.org/1161/STROKEAHA.114.006890
  3. Mair G, von Kummer R, Adami A, White PM, Adams ME, Yan B et al. Observer reliability of CT angiography in the assessment of acute ischaemic stroke: data from the Third International Stroke Trial. Neuroradiology 2014 October 7. http://dx.doi.org/10.1007/s00234-014-1441-0
  4. Impact of treatment delay, age and stroke severity of the effects of intravenous thrombolysis with alteplase in acute ischaemic stroke: an individual participant data meta-analysis of randomised trials Emberson J and the Stroke Thrombolysis Trialists Collaboration Lancet. 2014 Aug 5. pii: S0140-6736(14)60584-5. http://dx.doi.org/10.1016/S0140-6736(14)60584-5 .
  5. Mair G, Boyd EV, Chappell FM, von Kummer R, Lindley RI, Sandercock P, Wardlaw JM IST-3 Collaborative Group. Sensitivity and specificity of the Hyperdense Artery Sign for arterial obstruction in acute ischemic stroke Stroke (in press)
  6. Lindley RI, Wardlaw JM, Whiteley W, Cohen G, Blackwell B, Murray G, Sandercock P & the IST-3 Collaborative Group. Alteplase for acute ischemic stroke: outcomes by clinically important subgroups in the Third International Stroke Trial Stroke (submitted for publication)

Link to video of public lecture on stroke and thrombolysis by Peter Sandercock

http://www.ed.ac.uk/schools-departments/clinical-brain-sciences/news/latest-news/public-lectures-epilepsy-stroke

Editorials and commentaries on IST-3 since 2012

 

  1. Lyden PD. In anticipation of International Stroke Trial-3 (IST-3). Stroke 2012;43:1691-4
  2. Leys L, Cordonnier C. rt-PA for ischaemic stroke: what will the next question be?. Lancet 2012;379:2320-1
  3. Donnan GA, Davis SM. IST-3: a major contribution to thrombolysis research. International Journal of Stroke 2012;7:566-7
  4. Furlan AJ. IST-3: no pragmatic answers. International Journal of Stroke 2012;7:568-9
  5. Hoffman JR, Cooper RJ. How is more negative evidence being used to support claims of benefit: the curious case of the international stroke trial (IST-3). Emergency Medicine Australasia 2012;24:473-6
  6. Fatovich DM. Believing is seeing: stroke thrombolysis remains unproven after the third international stroke trial (IST-3). Emergency Medicine Australasia 2012;24:477-9
  7. Kleinig TJ, Churilov L, Parsch CS, Dewey HM, Barber PA. Stroke thrombolysis and the third international stroke trial: examining “the totality of the evidence”. Emergency Medicine Australasia 2012;25:107-9
  8. Hughes S. IST-3: tPA benefits sustained out to 18 months. Medscape. 2013. Article ID 806690. [http://www.medscape.com]
  9. Anderson C. Thrombolysis with alteplase after stroke: extending outcomes. Lancet Neurology 2013;12:731-2
  10. Evidence and doubt in the translation of research into care. Lancet 2014;384:638

Correspondence since 2012

 

  1. Fatovich DM, MacDonald SP, Brown SG, Smith B, Newman DH, Shreves AE, Barer D, Durtis D, Sandercock P, Wardlaw J, Dennis M, Murray G, Lindley R. Thrombolysis in acute ischaemic stroke. Lancet 2012;380:1053-5
  2. Shinton R, Sandercock P, Wardlaw JM, Hudson I. Questions about authorisation of alteplase for ischaemic stroke. Lancet 2014;384:659-63
  3. Dai Q, Sun W, Liu X,Whiteley WN, Thompson D, Sandercock P. Letter by Dai et al regarding article “Targeting recombinant tissue-type plasminogen activator in acute ischemic stroke based on risk of intracranial hemorrhage or poor functional outcome: an analysis of the Third International Stroke Trial”. Stroke 2014;45:e132-3

 

Abstracts published since trial results made public in 2012

  1. Sandercock P, Wardlaw JM, Lindley RI, Dennis MS, Cohen G. The third international stroke trial (IST-3) main results part I: primary and secondary outcomes among 3035 patients randomised. Cerebrovascular Diseases 2012;33 Suppl 2:16
  2. Lindley RI, Sandercock P, Wardlaw JW, Dennis MS, Cohen G. The third international stroke trial (IST-3) of thrombolysis main results III. Effect of iv thrombolysis with iv t-PA on death or dependency in the 3035 patients randomized: subgroup analysis. Cerebrovascular Diseases 2012;33(suppl 2):79 (Abst.1) [Ref 19448]
  3. Roots A, Birns J, Bhalla A, Rudd A. Nurse-led telemedicine-directed hyper-acute stroke trial randomisation and management of post-thrombolysis anaphylaxis. Cerebrovascular Diseases 2012;33(suppl 2):477-8 (Abst.2022) [Ref 19403]
  4. Farrall A, Wardlaw J, Sandercock P, Lindley R, Cohen G, von Kummer R, et al. The third international stroke trial (IST-3) of intravenous thrombolysis with rt-PA: baseline imaging features among 3035 patients randomised. International Journal of Stroke 2012;7 Suppl 2:61-2 (Abst.142)
  5. Sandercock P; IST-3 Collaborative Group. The Third International Stroke Trial (IST-3) of thrombolysis. Main results & implications for clinical practice. Cerebrovascular Diseases 2012;34 Suppl 1:6-7 (Abst.S5-1)
  6. Sandercock PAG, Wardlaw JM, Lindley RI, Cohen G; IST3 collaborative group. The third international stroke trial (IST-3) of intravenous rt-PA: effect of age and time on treatment effect among 3035 patients randomised. International Journal of Stroke 2012;7 Suppl 2:6
  7. Lindley RI, Sandercock PA, Wardlaw JM, Dennis MS, Cohen G, IST-3 Collaborative Group. Third international stroke trial (IST-3): subgroup effects of iv rt-PA < 6 hrs in acute ischemic stroke on symptomatic intracranial haemorrhage and outcome at 6 months. Stroke 2013;44 (Abst.TMP23)
  8. Sandercock PA, Wardlaw JM, Lindley RI, Dennis MS, IST-3 Collaborative Group. Third international stroke trial (IST-3): effect of iv rt-pa < 6 hours in acute ischaemic stroke on living circumstances and health related quality of life at six months. Stroke 2013;44 (Abst.WMP22)]
  9. Wardlaw J, Carpenter T, von Kummer R, Cohen G, Lindley R, Sandercock P. Perfusion imaging in patients randomised to rt-PA or control in the third international stroke trial (IST-3): baseline characteristics and association with outcome. Stroke 2013;44 (Abst.A10)
  10. Wardlaw J, von Kummer R, Farrall A, Cala L, von Heijne A, Peeters A, etal. The impact of ischemic and structural brain tissue changes on response to rt-PA: an analysis of imaging from 3035 patients in the third international stroke trial. Stroke 2013;44 (Abst.A104)
  11. Sandercock P, Wardlaw J, Dennis M, Cohen G, Whiteley W, Lindley, et al. Impact of thrombolysis on important aspects of daily life at 18 months in the third International Stroke Trial (IST-3). International Journal of Stroke 2013;8 Suppl 3:4
  12. Whiteley WN, Cohen G, Wardlaw J, Lindley R, Sandercock PAG. IST-3 trial: impact of rt-PA on survival to 18 months post ischaemic stroke. Cerebrovascular Diseases 2013;35(Suppl 3):19 (Abst.6)
  13. Sandercock PAG, Lindley RI, Wardlaw JM, Dennis MS, Cohen G. The third international stroke trial (IST-3): benefits of iv thrombolysis on functional outcome and health-related quality of life (HRQoL) persist to 18 months after treatment. Cerebrovascular Diseases 2013;35(Suppl 3):34 (Abst.4)
  14. Wardlaw JM, Carpenter T, Cohen G, von Kimmer R, Lindley R, Sandercock P. Does perfusion imaging lesion size or mismatch influence six month outcomes after rt-PA given up to six hours after acute ischaemic stroke? The third International Stroke Trial (IST-3). Cerebrovascular Diseases 2013;35(Suppl 3):111 (Abst.12)
  15. Whiteley WN, Thompson D, Cohen G, Lindley R, Wardlaw JM, Sandercock PAG. Predictions of intracranial haemorrhage and the risks and benefits of rtPA in acute ischaemic stroke: an analysis of the IST-3 trial. Cerebrovascular Diseases 2013;35(Suppl 3):169 (Abst.4)
  16. Mair G, Wardlaw JM, Sandercock P, Lindley R, von Kummer R. Combining CT angiography with non-contrast CT to predict infarct on follow up CT in acute ischaemic stroke. Substudy analysis of imaging from the third International Stroke Trial (IST-3). Cerebrovascular Diseases 2013;35(Suppl 3):237 (Abst.15)
  17. Mair G, Wardlaw JM, Sandercock P, Lindley R, von Kummer R, Farrall AJ. Association of non-contrast CT and CT angiography with baseline clinical deficit and functional outcome. Substudy analysis of imaging from the third International Stroke Trial (IST-3). Cerebrovascular Diseases 2013;35(Suppl 3):405 (Abst.226)
  18. Sakka E, Perry D, Buchanan D, Innes K, Sandercock P, Lindley RI, Wardlaw JM. Medical image management for multicentre trials. Experience from the Third International Stroke Trial (IST-3) with 6576 scans. Cerebrovascular Diseases 2013;35(Suppl 3):562 (Abst.24)
  19. Mair G, Wardlaw JM, von Kummer R, Sandercock PA. Response to thrombolysis treatment in ischemic stroke patients with and without arterial occlusion on computed tomographic angiography: the Third International Stroke Trial. Stroke 2014;45(Suppl 1) (Abst.A6)
  20. Khatri P, Tayama D, Cohen G, Lindley RI, Wardlaw JM, Yeatts SD, et al. Effect of IV rtPA in mild strokes in the third international stroke trial (IST3): a post hoc analysis. Stroke 2014;45(Suppl 1) (Abst.ATMP21)

 

 

 

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At the Congress of the European Neurological Society held in Barcelona, researchers are discussing the advantages and disadvantages of OPs or catheter interventions to eliminate thrombi and arteriosclerotic plaque in acute cases. New insights into molecular processes could be the key to medications for combatting dangerous oedemas following a stroke.

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Boehringer in end 2012 announced the approval in 15 European countries with the mutual recognition procedure, the extent of window treatment with alteplase, rt-PA in cases of acute ischemic stroke within 4 hours of symptom onset and after have ruled out the diagnosis of intracranial hemorrhage. The completion of the regulatory process has been reported by Germany, the Reference Member State, and will allow the implementation of this approval also to the European Union member states that adhere to the mutual recognition procedure. Alteplase is indicated for the fibrinolytic treatment of acute ischemic stroke, or for the dissolution of the clot that has blocked artery, helping to restore the normal blood flow, preventing or limiting damage to ischemic brain tissue. To achieve the greatest possible benefits, treatment should be initiated as early as possible after symptom onset. Alteplase was approved in 1987 for various indications in many countries, and since 1996 for the treatment of ischemic stroke with administration within three hours of the onset of symptoms. The combined analysis of the results of different studies, with placebo control group, showed that treatment with rt-PA within 180 minutes after the onset of ischemic symptoms allows more likely to residuare 30% in less than disability arising from ischemic damage compared to untreated patients or little or no disability after three months of the event compared to patients who did not receive thrombolytic therapy. An official statement by the Italian regulatory agency is likely to be soon released in early 2013. For many Italian hospitals until the official statement of the agency the use of alteplase will not be considered fully appropriate

Stroke Track is an Acute Stroke Checklist developed at Michigan University as a training toolk for iPhone.

It nicely reports demo data of the lysis candidate, NIH measurement as well as rTPA dosage.  This free app available at iTunes store together with MediMath represent the most relevant iPhone tool available for stroke in the3 acute phase and recovery. Sill much may be improved to offer a better tailored panel of stroke tool for trainees as well as stroke doctors

Microbubbles filled with xenon or other inhert gases as a drug delivery means in acute stroke are periodically reported in medical journals (circulation 2010) or newspapers as the latest frontier. This week the activities of the University College in London and Cincinnati/Houston University raised the attention of scientific journalists see at New Scientist and Daily Mail. But don’t panic this in US was just another experimental animal model. As usual with bubbles also Italians are there.

About the usefulness of a 3 tesla MRI in hyperacute phase of a stroke. The analysis showed unexpected results.

see at Diffusion-weighted MRI in acute stroke within the first 6 hours: 1.5 or 3.0 Tesla? by Rosso C, Drier A, Lacroix D, Mutlu G, Pires C, Lehéricy S, Samson Y, Dormont D. from AP-HP, Urgences Cérébro-Vasculaires, Université Pierre et Marie Curie, Paris VI, Hôpital Pitié-Salpêtrière, Paris