Safety and Efficacy of Intravenous Thrombolytic Therapy of Cerebral Infarction in Patients over 80 Years of Age

Czech version

Authors: M. Petrovicsová ¹; P. Kadlecová ²; D. Václavík ³; D. Šaňák ⁴; P. Ševčík ⁵; O. Škoda ⁶; R. Herzig ⁴; D. Školoudík ⁷; Z. Kalita ⁸; R. Mikulík ^2,9
Authors‘ workplace: Neurologické oddělení, Nemocnice Znojmo, příspěvková organizace ¹; Mezinárodní centrum klinického výzkumu (ICRC), FN u sv. Anny v Brně ²; Neurologické oddělení, Vítkovická nemocnice a. s., Ostrava-Vítkovice ³; Neurologická klinika LF UP a FN Olomouc ⁴; Neurologická klinika LF UK a FN Plzeň ⁵; Neurologické oddělení, Nemocnice Jihlava, příspěvková organizace ⁶; Neurologická klinika LF OU a Fakultní nemocnice Ostrava ⁷; Neurologické oddělení, Krajská nemocnice T. Bati, a. s., Zlín ⁸; I. neurologická klinika, FN u sv. Anny v Brně ⁹
Published in: Cesk Slov Neurol N 2012; 75/108(5): 581-585
Category: Original Paper

Overview

Background:
The benefit and risk of intravenous thrombolysis administered within 4.5 hours of symptom onset in over 80 years old patients with acute ischemic stroke is not well defined.

Aim:
To evaluate Czech data on the safety and efficacy of intravenous thrombolysis in patients older than 80 years.

Methods:
Czech Republic data recorded in the SITS registry (Safe Implementation of Treatments in Stroke) on patients treated with intravenous thrombolysis between Feb/2003 and Feb/2010 were analyzed. Mortality, the incidence of symptomatic intracerebral haemorrhage (SICH) and functional recovery following intravenous thrombolysis in patients >80 versus ≤80 years of age were compared. Multiple logistic regression analysis was used to adjust association between age and the outcome measures of baseline differences.

Results:
A total of 3,053 patients were treated with intravenous thrombolysis within 4.5 hours of symptom onset and, of these, 247 (8%) were >80 years old and 2,806 (92%) were ≤80 years old. In different stroke centres in the Czech Republic, patients >80 years of age represented 0–27% of all patients treated with intravenous thrombolysis. Patients >80 years old compared with those ≤80 years old had an identical rate of intracerebral haemorrhage (OR 1.08, 95% CI: 0.64 to 1.82), about two times higher mortality rate (OR 1.99, 95% CI: 1.37 to 2.90) and a tendency to less likely achieve modified Rankin scale 0–1 at three months (OR 0.77, 95% CI: 0.54 to 1.09).

Conclusion:
Patients >80 years old are being excluded from treatment with intravenous thrombolysis, even though intravenous thrombolysis has a similar safety profile in patients over 80 years as in younger patients. Our results are in accordance with the published data and suggest that there is no reason to exclude patients older than 80 years from treatment with intravenous thrombolysis.

Key words:
thrombolysis – cerebral infarction – elderly patients

Sources

1. Poppe AY, Hill MD. Acute ischaemic stroke in patients aged 80 years and older: focus on the tolerability of thrombolytic agents. Drugs Aging 2008; 25(2): 95–103.

2. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333(24): 1581–1587.

3. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995; 274(13): 1017–1025.

4. Di Carlo A, Lamassa M, Pracucci G, Basile AM, Trefoloni G, Vanni P et al. Stroke in the very old: clinical presentation and determinants of 3-month functional outcome: A European perspective. European BIOMED Study of Stroke Care Group. Stroke 1999; 30(11): 2313–2319.

5. ÚZIS ČR 2007. Dostupné z URL: www.uzis.cz.

6. World health organization. Dostupné z URL: www.who.int.

7. The demographics of aging. Dostupné z URL: www.transgenerational.org/aging/demographics.htm.

8. Bar M, Skoloudík D, Roubec M, Hradílek P, Chmelová J, Czerný D et al. Transcranial duplex sonography and CT angiography in acute stroke patients. J Neuroimaging 2010; 20(3): 240–245.

9. 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(12): 1095–1102.

10. Bar M, Sandercock P, Skoloudik D, Prochazka V. Should mechanical embolectomy devices be used in routine clinical practice? J Neural Transm 2011; 118(8): 1131–1138.

11. Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke 2005; 36(7): 1432–1438.

12. The European Stroke Organization (ESO) Executive Committee and the ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25(5): 457–507.

13. ESO: Guidelines Update – January 2009. Dostupné z URL: www.eso-stroke.org.

14. Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999; 282(21): 2019–2026.

15. Albers GW, Clark WM, Madden KP, Hamilton SA. ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. Stroke 2002; 33(2): 493–495.

16. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998; 352(9136): 1245–1251.

17. SITS. Dostupné z URL: www.acutestroke.org.

18. Kharitonova T, Mikulik R, Roine RO, Soinne L, Ahmed N, Wahlgren N. Association of early National Institutes of Health Stroke Scale improvement with vessel recanalization and functional outcome after intravenous thrombolysis in ischemic stroke. Stroke 2011; 42(6): 1638–1643.

19. Mikulik R, Ribo M, Hill MD, Grotta JC, Malkoff M, Molina C et al. Accuracy of serial National Institutes of Health Stroke Scale scores to identify artery status in acute ischemic stroke. Circulation 2007; 115(20): 2660–2665.

20. Engelter ST, Bonati LH, Lyrer PA. Intravenous thrombolysis in stroke patients of > or = 80 versus < 80 years of age-a systematic review across cohort studies. Age Ageing 2006; 35(6): 572–580.

21. Subgroup analysis of the NINDS t-PA Stroke Trial. Generalized efficacy of t-PA for acute stroke. Stroke 1997; 28(11): 2119–2125.

22. Mishra NK, Ahmed N, Andersen G, Egido JA, Lindsberg PJ, Ringleb PA et al. Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive. BMJ 2010; 341: c6046.

23. Bhatnagar P, Sinha D, Parker RA, Guyler P, O‘Brien A. Intravenous thrombolysis in acute ischaemic stroke: a systematic review and meta-analysis to aid decision making in patients over 80 years of age. J Neurol Neurosurg Psychiatry 2011; 82(7): 712–717.

24. Chen CI, Iguchi Y, Grotta JC, Garami Z, Uchino K, Shaltoni H et al. Intravenous TPA for very old stroke patients. Eur Neurol 2005; 54(3): 140–144.

25. Tanne D, Gorman MJ, Bates VE, Kasner SE, Scott P, Verro P et al. Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older: the tPA stroke survey experience. Stroke 2000; 31: 370–375.

26. Mouradian MS, Senthilselvan A, Jickling G, McCombe JA, Emery DJ, Dean N et al. Intravenous rt-PA for acute stroke: comparing its effectiveness in younger and older patients. J Neurol Neurosurg Psychiatry 2005; 76(9): 1234–1237.

27. Ringleb PA, Schwark C, Köhrmann M, Külkens S, Jüttler E, Hacke W et al. Thrombolytic therapy for acute ischaemic stroke in octogenarians: selection by magnetic resonance imaging improves safety but does not improve outcome. J Neurol Neurosurg Psychiatry 2007; 78(7): 690–693.

28. Sylaja PN, Cote R, Buchan AM, Hill MD. Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study. J Neurol Neurosurg Psychiatry 2006; 77(7): 826–829.

29. Berrouschot J, Röther J, Glahn J, Kucinski T, Fiehler J, Thomalla G. Outcome and severe hemorrhagic complications of intravenous thrombolysis with tissue plasminogen activator in very old (> or =80 years) stroke patients. Stroke 2005; 36(11): 2421–2425.

30. Toni D, Lorenzano S, Agnelli G, Guidetti D, Orlandi G, Semplicini A et al. Intravenous thrombolysis with rt-PA in acute ischemic stroke patients aged older than 80 years in Italy. Cerebrovasc Dis 2008; 25(1–2): 129–135.

31. Engelter ST, Reichhart M, Sekoranja L, Georgiadis D, Baumann A, Weder B et al. Thrombolysis in stroke patients aged 80 years and older: Swiss survey of IV thrombolysis. Neurology 2005; 65(11): 1795–1798.

32. Uyttenboogaart M, Schrijvers EM, Vroomen PC, De Keyser J, Luijckx GJ. Routine thrombolysis with intravenous tissue plasminogen activator in acute ischaemic stroke patients aged 80 years or older: a single centre experience. Age Ageing 2007; 36(5): 577–579.

33. Gómez-Choco M, Obach V, Urra X, Amaro S, Cervera A, Vargas M et al. The response to IV rt-PA in very old stroke patients. Eur J Neurol 2008; 15(3): 253–256.

34. Meseguer E, Labreuche J, Olivot JM, Abboud H, Lavallee PC, Simon O et al. Determinants of outcome and safety of intravenous rt-PA therapy in the very old: a clinical registry study and systematic review. Age Ageing 2008; 37(1): 107–111.

35. van Oostenbrugge RJ, Hupperts RM, Lodder J. Thrombolysis for acute stroke with special emphasis on the very old: experience from a single Dutch centre. J Neurol Neurosurg Psychiatry 2006; 77(3): 375–377.

36. Parnetti L, Silvestrelli G, Lanari A, Tambasco N, Capocchi G, Agnelli G. Efficacy of thrombolytic (rt-PA) therapy in old stroke patients: the Perugia Stroke Unit experience. Clin Exp Hypertens 2006; 28: 397–404.