Age-dependent clinical outcomes in primary versus oral anticoagulation-related intracerebral hemorrhage

Abstract

Aims

This study determined the influence of age on bleeding characteristics and clinical outcomes in primary spontaneous (non-OAC), vitamin K antagonist-related (VKA-) and non-vitamin K antagonist oral anticoagulant-related (NOAC-) ICH.

Methods

Pooled individual patient data of multicenter cohort studies were analyzed by logistic regression modelling and propensity-score-matching (PSM) to explore the influence of advanced age on clinical outcomes among non-OAC-, VKA-, and NOAC-ICH. Primary outcome measure was functional outcome at three months assessed by the modified Rankin Scale, dichotomized into favorable (mRS = 0–3) and unfavorable (mRS = 4–6) functional outcome. Secondary outcome measures included mortality, hematoma characteristics, and frequency of invasive interventions.

Results

In VKA-ICH 33.5% (670/2001), in NOAC-ICH 44.2% (69/156) and in non-OAC-ICH 25.2% (254/1009) of the patients were ≥80 years. After adjustment for treatment interventions and relevant parameters, elderly ICH patients comprised worse functional outcome at three months (adjusted odds ratio (aOR) in VKA-ICH: 1.49 (1.21–1.84); p < 0.001; NOAC-ICH: 2.01 (0.95–4.26); p = 0.069; non-OAC-ICH: 3.54 (2.50–5.03); p < 0.001). Anticoagulation was significantly associated with worse functional outcome below the age of 70 years, (aOR: 2.38 (1.78–3.16); p < 0.001), but not in patients of ≥70 years (aOR: 1.21 (0.89–1.65); p = 0.217). The differences in initial ICH volume and extent of ICH enlargement between OAC-ICH and non-OAC-ICH gradually decreased with increasing patient age.

Conclusions

As compared to elderly ICH-patients, in patients <70 years OAC-ICH showed worse clinical outcomes compared to non-OAC-ICH because of larger baseline ICH-volumes and extent of hematoma enlargement. Treatment strategies aiming at neutralizing altered coagulation should be aware of these findings.

Keywords

Intracerebral hemorrhage intracranial hemorrhage age anticoagulation

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References

GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390: 1211–1259.

Stein

Misselwitz

Hamann

Scharbrodt

Schummer

Oertel

. Intracerebral hemorrhage in the very old: future demographic trends of an aging population. Stroke 2012; 43: 1126–1128.

Furberg

Psaty

Manolio

Gardin

Smith

Rautaharju

. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994; 74: 236–241.

Mant

Hobbs

Fletcher

, 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.

Pisters

Lane

Nieuwlaat

de Vos

Crijns

Lip

. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138: 1093–1100.

Forti

Maioli

Domenico Spampinato

, et al. The effect of age on characteristics and mortality of intracerebral hemorrhage in the oldest-old. Cerebrovasc Dis 2016; 42: 485–492.

van Asch

Luitse

Rinkel

van der Tweel

Algra

Klijn

. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010; 9: 167–176.

Hemphill

3rd

JC Bonovich

Besmertis

Manley

Johnston

. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001; 32: 891–897.

Flibotte

Hagan

O'Donnell

Greenberg

Rosand

. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004; 63: 1059–1064.

10.

Silvain

Cayla

Hulot

, et al. High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study. Eur Heart J 2012; 33: 1241–1249.

11.

Cuisset

Quilici

Grosdidier

, et al. Comparison of platelet reactivity and clopidogrel response in patients </= 75 years versus > 75 years undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome. Am J Cardiol 2011; 108: 1411–1416.

12.

Abdelhafiz

Wheeldon

. Risk factors for bleeding during anticoagulation of atrial fibrillation in older and younger patients in clinical practice. Am J Geriatr Pharmacother 2008; 6: 1–11.

13.

Chao

Liu

Lin

, et al. Oral anticoagulation in very elderly patients with atrial fibrillation: a nationwide cohort study. Circulation 2018; 138: 37–47.

14.

Kuramatsu

Gerner

Schellinger

, et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA 2015; 313: 824–836.

15.

Kuramatsu

Sembill

Gerner

, et al. Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves. Eur Heart J 2018; 39: 1709–1723.

16.

Gerner

Kuramatsu

Sembill

, et al. Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Ann Neurol 2018; 83: 186–196.

17.

Sprugel

Kuramatsu

Gerner

, et al. Antiplatelet therapy in primary spontaneous and oral anticoagulation-associated intracerebral hemorrhage. Stroke 2018; 49: 2621–2629.

18.

Sprugel

Kuramatsu

Gerner

, et al. Presence of concomitant systemic cancer is not associated with worse functional long-term outcome in patients with intracerebral hemorrhage. Cerebrovasc Dis 2017; 44: 186–194.

19.

Sembill

Gerner

Volbers

, et al. Severity assessment in maximally treated ICH patients: The max-ICH score. Neurology 2017; 89: 423–431.

20.

Kasner

. Clinical interpretation and use of stroke scales. Lancet Neurol 2006; 5: 603–612.

21.

Zubkov

Mandrekar

Claassen

Manno

Wijdicks

Rabinstein

. Predictors of outcome in warfarin-related intracerebral hemorrhage. Arch Neurol 2008; 65: 1320–1325.

22.

Dowlatshahi

Demchuk

Flaherty

Ali

Lyden

Smith

. Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology 2011; 76: 1238–1244.

23.

Drake

Fisher

. Prognostic models and the propensity score. Int J Epidemiol 1995; 24: 183–187.

24.

Saez

Tobias

Munoz

Campbell

. A GEE moving average analysis of the relationship between air pollution and mortality for asthma in Barcelona, Spain. Stat Med 1999; 18: 2077–2086.

25.

Franchini

. Hemostasis and aging. Crit Rev Oncol Hematol 2006; 60: 144–151.

26.

Pezzini

Grassi

Paciaroni

, et al. Antithrombotic medications and the etiology of intracerebral hemorrhage: MUCH-Italy. Neurology 2014; 82: 529–535.

27.

O'Donnell

Xavier

Liu

, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet 2010; 376: 112–123.

28.

Dequatre-Ponchelle

Henon

Pasquini

, et al.

Vitamin K antagonists-associated cerebral hemorrhages: what are their characteristics?

Stroke 2013; 44: 350–355.

29.

Kremer

Jolink

Kappelle

Algra

Klijn

. Risk factors for lobar and non-lobar intracerebral hemorrhage in patients with vascular disease. PLoS One 2015; 10: e0142338.

30.

Zahuranec

Brown

Lisabeth

, et al. Early care limitations independently predict mortality after intracerebral hemorrhage. Neurology 2007; 68: 1651–1657.

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