Prevention and Treatment of Acute Stroke in the Nonagenarians and Beyond: Medical and Ethical Issues

  • Tiberiu A. Pana
  • Jesus A. Perdomo-Lampignano
  • Phyo K. MyintEmail author
Cerebrovascular Disorders (D Jamieson, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cerebrovascular Disorders


Purpose of review

As one of the fastest growing portions of the population, nonagenarians will constitute a significant percentage of the stroke patient population in the near future. Nonagenarians are nevertheless not specifically targeted by most clinical guidelines. In this review, we aimed to summarise the available evidence guiding stroke prevention and treatment in this age group.

Recent findings

Several recent observational studies have shown that the benefits of anticoagulation for the oldest old patients with atrial fibrillation may outweigh the bleeding risk. A sub-analysis of the IST-3 trial has shown for the first time that thrombolysis treatment in acute ischaemic stroke may be beneficial and safe even in octogenarian patients and older. Several recent observational studies have assessed thrombolysis in nonagenarians. The latest of these has shown better disability outcomes without increased rates of symptomatic intracerebral haemorrhage with thrombolysis.


Nonagenarian stroke patients may benefit from similar preventative and therapeutic strategies as their younger counterparts. A few important exceptions include primary prevention using aspirin or statins. Patient selection is nevertheless essential given the increased adverse event rates. Patient preference should play a key role in the decision-making process. Clinical trials including more nonagenarian patients are required to yield more robust evidence.


Stroke Cerebrovascular disease Nonagenarian Oldest old Prevention Management 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    United Nations, Department of Economic and Social Affairs, Population Division (2018) World Population Prospects: The 2017 Revision. Vol. I: Comprehensive Tables: World Population Prospects: The 2017 Revision; 2018 IIS 3080-S22.1; ST/ESA/SER.A/399.Google Scholar
  2. 2.
    Yazdanyar A, Newman AB. The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs. Clin Geriatr Med. 2009;25:563–77. Scholar
  3. 3.
    Prince MJ, Wu F, Guo Y, Gutierrez-Robledo LM, O'Donnell M, Sullivan R, et al. The burden of disease in older people and implications for health policy and practice. Lancet. 2015;385:549–62. Scholar
  4. 4.
    Russo T, Felzani G, Marini C. Stroke in the very old: a systematic review of studies on incidence, outcome, and resource use. J Aging Res. 2011;2011:108785–6. Scholar
  5. 5.
    Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137:e67–e492. Scholar
  6. 6.
    Kammersgaard LP, Jørgensen HS, Reith J, Nakayama H, Pedersen PM, Olsen TS. Short- and long-term prognosis for very old stroke patients. The Copenhagen Stroke Study. Age Ageing. 2004;33:149–54. Scholar
  7. 7.
    Luker JA, Wall K, Bernhardt J, Edwards I, Grimmer-Somers KA. Patients' age as a determinant of care received following acute stroke: a systematic review. BMC Health Serv Res. 2011;11:161. Scholar
  8. 8.
    Fonarow GC, Reeves MJ, Zhao X, Olson DM, Smith EE, Saver JL, et al. Age-related differences in characteristics, performance measures, treatment trends, and outcomes in patients with ischemic stroke. Circulation. 2010;121:879–91. Scholar
  9. 9.
    Sanossian N, Ovbiagele B. Prevention and management of stroke in very elderly patients. Lancet Neurol. 2009;8:1031–41. Scholar
  10. 10.
    Meschia JF, Cheryl B, Boden-Albala B, Braun LT, Bravata DM, Seemant C, et al. Guidelines for the primary prevention of stroke. Stroke. 2014;45:3754–832. Scholar
  11. 11.
    O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet. 2016;388:761–75. Scholar
  12. 12.
    Willey JZ, Moon YP, Sacco RL, Greenlee H, Diaz KM, Wright CB, et al. Physical inactivity is a strong risk factor for stroke in the oldest old: findings from a multi-ethnic population (the Northern Manhattan Study). Int J Stroke. 2017;12:197–200. Scholar
  13. 13.
    Mons U, Müezzinler A, Gellert C, Schöttker B, Abnet CC, Bobak M, et al. Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium. BMJ: Br Med J. 2015;350:h1551. Scholar
  14. 14.
    Sarikaya H, Ferro J, Arnold M. Stroke prevention - medical and lifestyle measures. Eur Neurol. 2015;73:150–7. Scholar
  15. 15.
    Hauer AJ, Ruigrok YM, Algra A, van Dijk EJ, Koudstaal PJ, Luijckx G, et al. Age-specific vascular risk factor profiles according to stroke subtype. J Am Heart Assoc. 2017;6:11–21. Scholar
  16. 16.
    Odden MC, Beilby PR, Peralta CA. Blood pressure in older adults: the importance of frailty. Curr Hypertens Rep. 2015;17:55. Scholar
  17. 17.
    Ferri C, Ferri L, Desideri G. Management of hypertension in the elderly and frail elderly. High Blood Press Cardiovasc Prev. 2017;24:1–11. Scholar
  18. 18.
    Benetos A, Rossignol P, Cherubini A, Joly L, Grodzicki T, Rajkumar C, et al. Polypharmacy in the aging patient: management of hypertension in octogenarians. JAMA. 2015;314:170–80. Scholar
  19. 19.
    Gueyffier F, Boutitie F, Boissel JP, Pocock S, Coope J, Cutler J, et al. Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men. A meta-analysis of individual patient data from randomized, controlled trials. The INDANA Investigators. Ann Intern Med. 1997;126:761–7. Scholar
  20. 20.
    Mukhtar O, Jackson SH. The hypertension in the very elderly trial - latest data. Br J Clin Pharmacol. 2013;75:951–4. Scholar
  21. 21.
    Benetos A, Bulpitt C, Petrovic M, Ungar A, Agabiti Rosei E, Cherubini A, et al. An expert opinion from the European Society of Hypertension–European Union Geriatric Medicine Society Working Group on the Management of Hypertension in very old, frail subjects. Hypertension. 2016;67:820–5. Scholar
  22. 22.
    Potter JF, Myint PK. Hypertension. In: Fillit HM, Rockwood K, Young J, et al., editors. Brocklehurst’s textbook of geriatric medicine and gerontology. 8th ed. Philadelphia: Elsevier; 2017. p. 295.Google Scholar
  23. 23.
    Savarese G, Gotto AM Jr, Paolillo S, D'Amore C, Losco T, Musella F, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2013;62:2090–9. Scholar
  24. 24.
    Teng M, Lin L, Zhao YJ, Khoo AL, Davis BR, Yong QW, et al. Statins for primary prevention of cardiovascular disease in elderly patients: systematic review and meta-analysis. Drugs Aging. 2015;32:649–61. Scholar
  25. 25.
    Ramos R, Comas-Cufí M, Martí-Lluch R, Balló E, Ponjoan A, Alves-Cabratosa L, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ. 2018;362:k3359. Scholar
  26. 26.
    Sundvall H, Fastbom J, Wallerstedt SM, Vitols S. Use of statins in the elderly according to age and indication-a cross-sectional population-based register study. Eur J Clin Pharmacol. 2019. Scholar
  27. 27.
    Meador BM, Huey KA. Statin-associated myopathy and its exacerbation with exercise. Muscle Nerve. 2010;42:469–79. Scholar
  28. 28.
    Campins L, Camps M, Riera A, Pleguezuelos E, Yebenes JC, Serra-Prat M. Oral drugs related with muscle wasting and sarcopenia. A Review. Pharmacology. 2017;99:1–8. Scholar
  29. 29.
    Goldstein LB, Amarenco P, Szarek M, Callahan A 3rd, Hennerici M, Sillesen H, et al. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology. 2008;70:2364–70.CrossRefGoogle Scholar
  30. 30.
    Manktelow BN, Potter JF. Interventions in the management of serum lipids for preventing stroke recurrence. Cochrane Database Syst Rev. 2009;3:CD002091. Scholar
  31. 31.
    Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81. Scholar
  32. 32.
    Hackam DG, Woodward M, Newby LK, Bhatt DL, Shao M, Smith EE, et al. Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis. Circulation. 2011;124:2233–42. Scholar
  33. 33.
    McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke. 2012;43:2149–56. Scholar
  34. 34.
    Ziff OJ, Banerjee G, Ambler G, Werring DJ. Statins and the risk of intracerebral haemorrhage in patients with stroke: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2019;90:75–83. Scholar
  35. 35.
    Elwood P, Morgan G, White J, Dunstan F, Pickering J, Mitchell C, et al. Aspirin taking in a South Wales county. Br J Cardiol. 2011;18.
  36. 36.
    Mostaza JM, Lahoz C, Salinero-Fort MA, Cardenas J. Cardiovascular disease in nonagenarians: prevalence and utilization of preventive therapies. Eur J Prev Cardiol. 2018;204748731881372. Scholar
  37. 37.
    Montalescot G. A farewell to aspirin in primary prevention? Nat Rev Cardiol. 2019;16:76–7. Scholar
  38. 38.
    Ridker PM. Should aspirin be used for primary prevention in the post-statin era? N Engl J Med. 2018;379:1572–4. Scholar
  39. 39.
    McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379:1509–18. Scholar
  40. 40.
    Hankey GJ. The benefits of aspirin in early secondary stroke prevention. Lancet. 2016;388:312–4. Scholar
  41. 41.
    Li L, Geraghty OC, Mehta Z, Rothwell PM, Oxford Vascular Study. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet. 2017;390:490–9. Scholar
  42. 42.
    Chen Z, Sandercock P, Pan H, Counsell C, Collins R, Liu L, et al. Indications for early aspirin use in acute ischemic stroke. Stroke. 2000;31:1240–9. Scholar
  43. 43.
    Hao Q, Tampi M, O’Donnell M, Foroutan F, Siemieniuk RAC, Guyatt G. Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis. BMJ. 2018;363:k5108. Scholar
  44. 44.
    Spagnoli L, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz RS, et al. Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA. 2004;292:1845–52. Scholar
  45. 45.
    Barkat M, Roy I, Antoniou SA, Torella F, Antoniou GA. Systematic review and network meta-analysis of treatment strategies for asymptomatic carotid disease. Sci Rep. 2018;8:4458–13. Scholar
  46. 46.
    Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160–236. Scholar
  47. 47.
    Meschia J, Bushnell C, Boden-Albala B, Braun L, Bravata D, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:3754–832. Scholar
  48. 48.
    Schneider JR, Jackson CR, Helenowski IB, Verta MJ, Wilkinson JB, Kim S, et al. A comparison of results of carotid endarterectomy in octogenarians and nonagenarians to younger patients from the Mid-America Vascular Study Group and the Society for Vascular Surgery Vascular Quality Initiative. J Vasc Surg. 2017;65:1643–52. Scholar
  49. 49.
    Ballotta E, Toniato A, Farina F, Baracchini C. The perioperative outcomes of eversion carotid endarterectomy in diabetic patients aged 80 years or older. J Vasc Surg. 2016;64:348–53. Scholar
  50. 50.
    Ballotta E, Toniato A, Da Roit A, Lorenzetti R, Piatto G, Baracchini C. Carotid endarterectomy for asymptomatic carotid stenosis in the very elderly. J Vasc Surg. 2015;61:382–8. Scholar
  51. 51.
    Okawa M, Ogata T, Abe H, Fukuda K, Higashi T, Inoue T. Do octogenarians still have a high risk of adverse outcomes after carotid endarterectomy in the era of a super-aged society? A single-center study in Japan. J Stroke Cerebrovasc Dis. 2015;24:370–3. Scholar
  52. 52.
    Sadideen H, Thomson DR, Lewis RR, Padayachee TS, Taylor PR. Carotid endarterectomy in the elderly: risk factors, intraoperative carotid hemodynamics and short-term complications: a UK tertiary center retrospective analysis. Vascular. 2013;21:273–7. Scholar
  53. 53.
    Rajamani K, Kennedy KF, Ruggiero NJ, Rosenfield K, Spertus J, Chaturvedi S. Outcomes of carotid endarterectomy in the elderly: report from the National Cardiovascular Data Registry. Stroke. 2013;44:1172–4. Scholar
  54. 54.
    De Rango P, Lenti M, Simonte G, Cieri E, Giordano G, Caso V, et al. No benefit from carotid intervention in fatal stroke prevention for >80-year-old patients. Eur J Vasc Endovasc Surg. 2012;44:252–9. Scholar
  55. 55.
    Voeks JH, Howard G, Roubin GS, Malas MB, Cohen DJ, Sternbergh WC, et al. Age and outcomes after carotid stenting and endarterectomy: the carotid revascularization endarterectomy versus stenting trial. Stroke. 2011;42:3484–90. Scholar
  56. 56.
    Schmidt M, Ulrichsen SP, Pedersen L, Botker HE, Nielsen JC, Sorensen HT. 30-year nationwide trends in incidence of atrial fibrillation in Denmark and associated 5-year risk of heart failure, stroke, and death. Int J Cardiol. 2016;225:30–6. Scholar
  57. 57.
    Howard G, Roubin GS, Jansen O, Hendrikse J, Halliday A, Fraedrich G, et al. Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials. Lancet. 2016;387:1305–11. Scholar
  58. 58.•
    Antoniou GA, Georgiadis GS, Georgakarakos EI, Antoniou SA, Bessias N, Smyth JV, et al. Meta-analysis and meta-regression analysis of outcomes of carotid endarterectomy and stenting in the elderly. JAMA Surg. 2013;148:1140–52. Meta-analysis of observational studies including > 500,000 CEA procedures showing that patients over 80 years of age have the same neurological outcomes, but higher mortality than their younger counterparts.CrossRefGoogle Scholar
  59. 59.
    Wach MM, Dumont TM, Shakir HJ, Snyder KV, Hopkins LN, Levy EI, et al. Carotid artery stenting in nonagenarians: are there benefits in surgically treating this high risk population? J Neurointerv Surg. 2015;7:182–7. Scholar
  60. 60.
    Bonati LH, Fraedrich G, Carotid Stenting Trialists’ Collaboration. Age modifies the relative risk of stenting versus endarterectomy for symptomatic carotid stenosis--a pooled analysis of EVA-3S, SPACE and ICSS. Eur J Vasc Endovasc Surg. 2011;41:153–8. Scholar
  61. 61.
    Bonati LH, Dobson J, Algra A, Branchereau A, Chatellier G, Fraedrich G, et al. Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data. Lancet. 2010;376:1062–73. Scholar
  62. 62.•
    Heo SH, Bushnell CD. Factors influencing decision making for carotid endarterectomy versus stenting in the very elderly. Front Neurol. 2017;8:220. Recent extensive review of existing literature about the choice of CEA vs CAS in the very elderly.
  63. 63.
    • Mott M, Koroshetz W, Wright CB. CREST-2: Identifying the best method of stroke prevention for carotid artery stenosis: National Institute of Neurological Disorders and Stroke Organizational Update. Stroke. 2017;48:e130. CREST-2 trial: sub-analysis of upcoming results may provide more robust data on the issue of carotid intervention in the very elderly.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Melin AA, Schmid KK, Lynch TG, Pipinos II, Kappes S, Longo GM, et al. Preoperative frailty Risk Analysis Index to stratify patients undergoing carotid endarterectomy. J Vasc Surg. 2015;61:683–9. Scholar
  65. 65.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–962. Scholar
  66. 66.
    Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137:263–72. Scholar
  67. 67.
    Alnsasra H, Haim M, Senderey AB, Reges O, Leventer-Roberts M, Arnson Y, et al. Net clinical benefit of anticoagulant treatments in elderly patients with nonvalvular atrial fibrillation: experience from the real world. Heart Rhythm. 2019;16:31–7. Scholar
  68. 68.
    Ekerstad N, Karlsson T, Soderqvist S, Karlson BW. Hospitalized frail elderly patients - atrial fibrillation, anticoagulation and 12 months’ outcomes. Clin Interv Aging. 2018;13:749–56. Scholar
  69. 69.
    Biteker M, Basaran O, Dogan V, Beton O, Tekinalp M, Cagri Aykan A, et al. Real-life use of digoxin in patients with non-valvular atrial fibrillation: data from the RAMSES study. J Clin Pharm Ther. 2016;41:711–7. Scholar
  70. 70.
    Shurrab M, Crystal E, O’Donnell D, Navare H, Neves P, Khatib R, et al. The gap between indicated and prescribed stroke prevention therapies in a high-risk geriatric population. J Interv Card Electrophysiol. 2017;48:261–6. Scholar
  71. 71.
    McGrath ER, Go AS, Chang Y, Borowsky LH, Fang MC, Reynolds K, et al. Use of oral anticoagulant therapy in older adults with atrial fibrillation after acute ischemic stroke. J Am Geriatr Soc. 2017;65:241–8. Scholar
  72. 72.
    Oqab Z, McIntyre WF, Quinn KL, Lamb T, Quadros K, Yazdan-Ashoori P, et al. Resident physicians choices of anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation. Can J Cardiol. 2016;32:824–8. Scholar
  73. 73.
    Yamashita Y, Hamatani Y, Esato M, Chun Y, Tsuji H, Wada H, et al. Clinical characteristics and outcomes in extreme elderly (age >/= 85 years) Japanese patients with atrial fibrillation: the Fushimi AF registry. Chest. 2016;149:401–12. Scholar
  74. 74.
    • Chao T, Liu C, Lin Y, Chang S, Lo L, Hu Y, et al. Oral anticoagulation in very elderly patients with atrial fibrillation: a nationwide cohort study. Circulation. 2018;138:37–47. Large observational study showing OAC benefit in nonagenarians.CrossRefPubMedGoogle Scholar
  75. 75.
    Proietti M, Mairesse GH, Goethals P, Scavee C, Vijgen J, Blankoff I, et al. A population screening programme for atrial fibrillation: a report from the Belgian Heart Rhythm Week screening programme. Europace. 2016;18:1779–86. Scholar
  76. 76.
    Hugo GS, Figueiras-Graillet LM, Anguita M, Marin F, Bertomeu V, Roldan I, et al. Oral anticoagulation in octogenarians with atrial fibrillation. Int J Cardiol. 2016;223:87–90. Scholar
  77. 77.
    Lefebvre MC, St-Onge M, Glazer-Cavanagh M, Bell L, Kha Nguyen JN, Viet-Quoc Nguyen P, et al. The effect of bleeding risk and frailty status on anticoagulation patterns in octogenarians with atrial fibrillation: the FRAIL-AF Study. Can J Cardiol. 2016;32:169–76. Scholar
  78. 78.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2016;50:E88. Scholar
  79. 79.
    • Patti G, Lucerna M, Pecen L, Siller-Matula JM, Cavallari I, Kirchhof P, et al. Thromboembolic risk, bleeding outcomes and effect of different antithrombotic strategies in very elderly patients with atrial fibrillation: a sub-analysis from the PREFER in AF (PREvention oF Thromboembolic Events-European Registry in Atrial Fibrillation). J Am Heart Assoc. 2017;6:e005657. Large observational study showing OAC benefit in over 85s.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Lip G, Clementy N, Pericart L, Banerjee A, Fauchier L. Stroke and major bleeding risk in elderly patients aged ≥75 years with atrial fibrillation: the Loire Valley Atrial Fibrillation Project. Stroke. 2015;46:143–50. Scholar
  81. 81.
    • Rash A, Downes T, Portner R, Yeo WW, Morgan N, Channer KS. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age and Ageing. 2007;36:151–6. Clinical trial showing OAC benefit in > 80s.CrossRefPubMedGoogle Scholar
  82. 82.
    • Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370:493–503. Clinical Trial showing OAC benefit in > 80s.CrossRefPubMedGoogle Scholar
  83. 83.
    Hagerty T, Rich MW. Fall risk and anticoagulation for atrial fibrillation in the elderly: a delicate balance. Cleve Clin J Med. 2017;84:35–40. Scholar
  84. 84.
    Sellers MB, Newby KL. Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients. Am Heart J. 2011;161:241–6. Scholar
  85. 85.
    Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med. 1999;159:677–85. Scholar
  86. 86.
    Oertel LB, Fogerty AE. Use of direct oral anticoagulants for stroke prevention in elderly patients with nonvalvular atrial fibrillation. J Am Assoc Nurse Pract. 2017;29:551–61. Scholar
  87. 87.
    Giustozzi M, Vedovati MC, Verso M, Scrucca L, Conti S, Verdecchia P, et al. Patients aged 90years or older with atrial fibrillation treated with oral anticoagulants: a multicentre observational study. Int J Cardiol. 2019;281:56–61.CrossRefGoogle Scholar
  88. 88.
    Lauw MN, Eikelboom JW, Coppens M, Wallentin L, Yusuf S, Ezekowitz M, et al. Effects of dabigatran according to age in atrial fibrillation. Heart. 2017;103:1015–23. Scholar
  89. 89.
    Levy JH, Douketis J, Weitz JI. Reversal agents for non-vitamin K antagonist oral anticoagulants. Nat Rev Cardiol. 2018;15:273–81. Scholar
  90. 90.
    Forbes HL, Polasek TM. Potential drug-drug interactions with direct oral anticoagulants in elderly hospitalized patients. Ther Adv Drug Saf. 2017;8:319–28. Scholar
  91. 91.
    Tonelli M, Riella M. Chronic kidney disease and the aging population. Am J Physiol Ren Physiol. 2014;306:469–72. Scholar
  92. 92.
    Keskar V, McArthur E, Wald R, Harel Z, Zimmerman D, Molnar AO, et al. The association of anticoagulation, ischemic stroke, and hemorrhage in elderly adults with chronic kidney disease and atrial fibrillation. Kidney Int. 2017;91:928–36. Scholar
  93. 93.
    van Bemmel T, Delgado V, Bax JJ, Gussekloo J, Blauw GJ, Westendorp RG, et al. Impact of valvular heart disease on activities of daily living of nonagenarians: the Leiden 85-plus study a population based study. BMC Geriatr. 2010;10:17. Scholar
  94. 94.
    Charidimou A, Shakeshaft C, Werring DJ. Cerebral microbleeds on magnetic resonance imaging and anticoagulant-associated intracerebral hemorrhage risk. Front Neurol. 2012;3:133. Scholar
  95. 95.
    Wilson D, Ambler G, Shakeshaft C, Brown MM, Charidimou A, Al-Shahi Salman R, et al. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol. 2018;17:539–47.CrossRefGoogle Scholar
  96. 96.
    Charidimou A, Karayiannis C, Song TJ, Orken DN, Thijs V, Lemmens R, et al. Brain microbleeds, anticoagulation, and hemorrhage risk: meta-analysis in stroke patients with AF. Neurology. 2017;89:2317–26. Scholar
  97. 97.
    Aonuma K, Yamasaki H, Nakamura M, Ootomo T, Takayama M, Ando K, et al. Percutaneous WATCHMAN left atrial appendage closure for Japanese patients with nonvalvular atrial fibrillation at increased risk of thromboembolism ― first results from the SALUTE trial. Circ J. 2018;82:2946–53. Scholar
  98. 98.
    Holmes J, David R, Kar S, Price MJ, Whisenant B, Sievert H, et al. Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014;64:1–12. Scholar
  99. 99.
    Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet. 2009;374:534–42. Scholar
  100. 100.
    Reddy VY, Doshi SK, Kar S, Gibson DN, Price MJ, Huber K, et al. 5-year outcomes after left atrial appendage closure. J Am Coll Cardiol. 2017;70:2964–75. Scholar
  101. 101.
    Ronco F, Mazzone P, Hosseinian L, Genovesi S. Recent advances in stroke prevention in patients with atrial fibrillation and end-stage renal disease. Cardiorenal Med. 2017;7:207–17. Scholar
  102. 102.
    Davtyan KV, Kalemberg AA, Topchyan AH, Simonyan GY, Bazaeva EV, Shatahtsyan VS. Left atrial appendage occluder implantation for stroke prevention in elderly patients with atrial fibrillation: acute and long-term results. J Geriatr Cardiol. 2017;14:590–2. Scholar
  103. 103.
    Piccini JP, Sievert H, Patel MR. Left atrial appendage occlusion: rationale, evidence, devices, and patient selection. Eur Heart J. 2017;38:869. Scholar
  104. 104.
    Ford GA. Thrombolysis for stroke in the over 80s. Age Ageing. 2004;33:95–7. Scholar
  105. 105.
    •• Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, et al. 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;379:2352–63. IST-3 trial; First trial to show no difference in thrombolysis outcomes between > 80s and < 80s (subgroup analysis).CrossRefPubMedGoogle Scholar
  106. 106.
    Wardlaw JM, Sandercock P, Cohen G, Farrall A, Lindley RI, Von Kummer R, et al. Association between brain imaging signs, early and late outcomes, and response to intravenous alteplase after acute ischaemic stroke in the third International Stroke Trial (IST-3): secondary analysis of a randomised controlled trial. Lancet Neurol. 2015;14:485–96. Scholar
  107. 107.
    •• Berge E, Cohen G, Roaldsen MB, Lundstrom E, Isaksson E, Rudberg AS, et al. Effects of alteplase on survival after ischaemic stroke (IST-3): 3 year follow-up of a randomised, controlled, open-label trial. Lancet Neurol. 2016;15:1028–34. IST-3 post hoc analysis showing thrombolysis-related decreases in 3-year mortality in octogenarians.CrossRefPubMedGoogle Scholar
  108. 108.••
    Wardlaw JM, Murray V, Berge E and del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014;CD000213. Cochrane review showing good disability and mortality outcomes with thrombolysis in > 80s (subgroup analysis).
  109. 109.
    •• Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384:1929–35. Meta-analysis showing no benefit with thrombolysis in octogenarians with a treatment delay longer than 3 h.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Engelter ST, Bonati LH, Lyrer PA. Intravenous thrombolysis in stroke patients of ≥ 80 versus < 80 years of age - a systematic review across cohort studies. Age Ageing. 2006;35:572–80. Scholar
  111. 111.
    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;82:712–7. Scholar
  112. 112.
    Pego PM, Nunes AP, Ferreira P, Sousa C, Amaral-Silva A. Thrombolysis in patients aged over 80 years is equally effective and safe. J Stroke Cerebrovasc Dis. 2016;25:1532–8. Scholar
  113. 113.
    Matsuo R, Kamouchi M, Fukuda H, Hata J, Wakisaka Y, Kuroda J, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for ischemic stroke patients over 80 years old: the Fukuoka Stroke Registry. PLoS One. 2014;9:e110444. Scholar
  114. 114.
    Takayanagi S, Ochi T, Hanakita S, Suzuki Y, Maeda K. The safety and effectiveness of low-dose recombinant tissue plasminogen activator (0.6 mg/kg) therapy for elderly acute ischemic stroke patients (≥ 80 years old) in the pre-endovascular era. Neurol Med Chir. 2014;54:435–40. Scholar
  115. 115.
    Manawadu D, Bodla S, Keep J, Kalra L. Influence of age on thrombolysis outcome in wake-up stroke. Stroke. 2013;44:2898–900. Scholar
  116. 116.
    Pornpatr DA, Sombat M, Junya P, Permphan D. Stroke outcomes in Thai elderly patients treated with and without intravenous thrombolysis. Neurol Int. 2013;5:e15. Scholar
  117. 117.
    Busl KM, Nogueira RG, Yoo AJ, Hirsch JA, Schwamm LH, Rost NS. Prestroke dementia is associated with poor outcomes after reperfusion therapy among elderly stroke patients. J Stroke Cerebrovasc Dis. 2013;22:718–24. Scholar
  118. 118.
    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;341:1144. Scholar
  119. 119.
    Bray BD, Campbell J, Hoffman A, Tyrrell PJ, Wolfe CDA, Rudd AG. Stroke thrombolysis in England: an age stratified analysis of practice and outcome. Age Ageing. 2013;42:240–5. Scholar
  120. 120.
    Pundik S, McWilliams-Dunnigan L, Blackham KL, Kirchner HL, Sundararajan S, Sunshine JL, et al. Older age does not increase risk of hemorrhagic complications after intravenous and/or intra-arterial thrombolysis for acute stroke. J Stroke Cerebrovasc Dis. 2008;17:266–72. Scholar
  121. 121.
    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;78:690–3. Scholar
  122. 122.
    Berrouschot J, Rother J, Glahn J, Kucinski T, Fiehler J, Thomalla G. Outcome and severe hemorrhagic complications of intravenous thrombolysis with tissue plasminogen activator in very old (>=80 years) stroke patients. Stroke. 2005;36:2421–5. Scholar
  123. 123.
    Simon JE, Sandler DL, Warwick-Pexman JH, Hill MD, Buchan AM. Is intravenous recombinant tissue plasminogen activator (rt-PA) safe for use in patients over 80 years old with acute ischaemic stroke? - the Calgary experience. Age Ageing. 2004;33:143–9. Scholar
  124. 124.
    Girotra T, Almallouhi E, Al Kasab S, Banerjee C, Turner NL, Debenham E, et al. Functional outcomes of intravenous thrombolysis in octogenarians and nonagenarians through telestroke: single-center experience. Telemed J E Health. 2019.
  125. 125.
    García-Caldentey J, Alonso de Leciñana M, Simal P, Fuentes B, Reig G, Díaz-Otero F, et al. Intravenous thrombolytic treatment in the oldest old. Stroke Res Treat. 2012;2012:923676–7. Scholar
  126. 126.
    • Sarikaya H, Arnold M, Engelter ST, Lyrer PA, Michel P, Odier C, et al. Intravenous thrombolysis in nonagenarians with ischemic stroke. Stroke. 2011;42:1967–70. Observational study assessing thrombolysis outcomes in nonagenarians.CrossRefPubMedGoogle Scholar
  127. 127.
    • Behrouz R, Masjuán-Vallejo J, Vera R, Willey JZ, Zedet M, Moulin S, et al. Outcomes of nonagenarians with acute ischemic stroke treated with intravenous thrombolytics. J Stroke Cerebrovasc Dis. 2018;27:246–56. Observational study assessing thrombolysis outcomes in nonagenarians.CrossRefPubMedGoogle Scholar
  128. 128.
    • Sagnier S, Galli P, Poli M, Debruxelles S, Renou P, Olindo S, et al. The impact of intravenous thrombolysis on outcome of patients with acute ischemic stroke after 90 years old. BMC Geriatr. 2016;16:156. Observational study assessing thrombolysis outcomes in nonagenarians.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    • Mateen FJ, Nasser M, Spencer BR, Freeman WD, Shuaib A, Demaerschalk BM, et al. Outcomes of intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 90 years or older. Mayo Clin Proc. 2009;84:334–8. Observational study assessing thrombolysis outcomes in nonagenarians.CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    • Montero-Ruiz-de-Gamboa V, Suazo-Vacarezza C, Ramírez-Méndez I, Bastías-Barra P, Hoppe-Wiegering A, Barrueto A. Intravenous thrombolysis in acute ischemic stroke of nonagenarian patients: a single center experience in Chile. J Neurol Sci. 2015;357:e397. Observational study assessing thrombolysis outcomes in nonagenarians.CrossRefGoogle Scholar
  131. 131.
    Falk-Delgado A, Kuntze-Söderqvist Å, Fransén J, Falk-Delgado A. Improved clinical outcome 3 months after endovascular treatment, including thrombectomy, in patients with acute ischemic stroke: a meta-analysis. J Neurointerv Surg. 2016;8:665–70. Scholar
  132. 132.
    Bracard S, Ducrocq X, Mas JL, Soudant M, Oppenheim C, Moulin T, et al. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol. 2016;15:1138–47. Scholar
  133. 133.
    Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378:11–21. Scholar
  134. 134.
    Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372:2296–306. Scholar
  135. 135.
    Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372:1019–30. Scholar
  136. 136.
    Campbell BCV, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372:1009–18. Scholar
  137. 137.
    Berkhemer OA, Fransen PSS, Beumer D, van den Berg LA, van den Berg R, van den Berg JSP, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11–20. Scholar
  138. 138.
    •• Goyal M, Menon BK, van Zwam WH, Dippel DWJ, Mitchell PJ, Demchuk AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387:1723–31. Meta-analysis showing the same benefit derived from thrombectomy in patients > 80s as in other age groups (subgroup analysis).CrossRefPubMedGoogle Scholar
  139. 139.
    • Jeon JP, Kim S, Kim CH. Endovascular treatment of acute ischemic stroke in octogenarians: a meta-analysis of observational studies. Clin Neurol Neurosurg. 2017;161:70–7. Meta-analysis of observational studies showing similar recanalization rates with thrombectomy between > 80s and younger patients.CrossRefPubMedGoogle Scholar
  140. 140.
    Khan MA, Baird GL, Miller D, Patel A, Tsekhan S, Yaghi S, et al. Endovascular treatment of acute ischemic stroke in nonagenarians compared with younger patients in a multicenter cohort. J NeuroInterv Surg. 2017;9:727–31. Scholar
  141. 141.
    Möhlenbruch M, Pfaff J, Schönenberger S, Nagel S, Bösel J, Herweh C, et al. Endovascular stroke treatment of nonagenarians. AJNR. Am J Neuroradiol. 2017;38:299–303. Scholar
  142. 142.
    Chiquete E, Ruiz-Sandoval MC, Álvarez-Palazuelos LE, Padilla-Martínez JJ, González-Cornejo S, Ruiz-Sandoval JL. Hypertensive intracerebral hemorrhage in the very elderly. Cerebrovasc Dis. 2007;24:196–201. Scholar
  143. 143.
    Inoue Y, Miyashita F, Minematsu K, Toyoda K. Clinical characteristics and outcomes of intracerebral hemorrhage in very elderly. J Stroke Cerebrovasc Dis. 2018;27:97–102. Scholar
  144. 144.
    Guo R, Chen R, Yu Z, Tian R, Ren Y, You C, et al. Clinical features and prognosis of primary intraventricular hemorrhage in elderly: single-center experience. World Neurosurg. 2019;124:e445–52. Scholar
  145. 145.
    Charidimou A, Imaizumi T, Moulin S, Biffi A, Samarasekera N, Yakushiji Y, et al. Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: a meta-analysis. Neurology. 2017;89:820–9. Scholar
  146. 146.
    Xu X, Vestesson E, Paley L, Desikan A, Wonderling D, Hoffman A, et al. The economic burden of stroke care in England, Wales and Northern Ireland: using a national stroke register to estimate and report patient-level health economic outcomes in stroke. Eur Stroke J. 2018;3:82–91. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Tiberiu A. Pana
    • 1
  • Jesus A. Perdomo-Lampignano
    • 1
  • Phyo K. Myint
    • 1
    • 2
    Email author
  1. 1.Ageing Clinical and Experimental Research Team, Institute of Applied Health Sciences, School of Medicine, Medical Sciences & NutritionUniversity of AberdeenAberdeenUK
  2. 2.School of Medicine, Medical Sciences and NutritionAberdeenScotland, UK

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