relationships between age, other predictive variables, and 90-day functional outcome after iv...
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Relationships between age, other predictive variables, and the 90-day functional outcome after intravenous thrombolysis for acute ischemic stroke
Roshan Gunathilake, Venkatesh Krishnamurthy, Christopher Oldmeadow, Erin Kerr, Chandrasekhara Padmakumar, John Attia, Mark Parsons and Christopher Levi
Departments of General Medicine, Neurology, and Geriatric Medicine John Hunter Hospital ANDHunter Medical Research InstituteNewcastle, NSW
Introduction
• Strong data to support use of IV thrombolysis regardless of age1
• Absolute benefit is attenuated in older patients, but the relative benefit is retained2
• Careful patient selection is important• Traditional statistical methods used in previous
studies have limited utility in classifying patients into risk categories3
Objective• To examine the relationships between – age–other recognised predictor variables, and –90-day outcome following IV thrombolysis among acute stroke victims presenting to an Australian tertiary centre
• using classification and regression trees (CART)4
Methods• Design: observational study using
prospectively collected data (TIPS database)• Setting: Acute Stroke Service, John Hunter
Hospital, NSW• Subjects: All acute stroke patients treated with
rt-PA between Jan 2011 – Jun 2013• Thrombolysis protocol5: rt-PA within 4.5h, no
upper age limit , NCCT+ CTA
Methods• Follow up: 90 day clinical review/ telephone interview• Ethics approval: HNE Human Research Ethics Committee• Measurements: – Baseline clinical variables – Alberta Stroke Program Early CT Scale (ASPECTS)6 – Modified leptomeningeal collateral score7
– 90-day modified Rankin score [dichotomized to <2 (good outcome) or ≥2 (poor outcome)
Imaging analysis
• Baseline NCCT and CTA independently reviewed and scored by consensus by 2 authors (RG, VK)
• ASPECTS6 to assess the EIC in 2 axial cuts (score 0- 10)
• Leptomeningeal collateral Grading (modified after Tan et al.)7 based on contrast opacification in arteries distal to an occlusion (score 0- 2)
Statistical analysis• Student’s t test, Mann Whitney U test and Fisher’s
exact test for descriptive statistics• CART analysis (RPART library R2.15) to determine
which baseline variables predicted 90-day outcome (dichotomized according to mRS <2 or ≥2)
• Variables included in CART: Age1, gender, premorbid mRS, NIHSS8, ASPECTS6, Collateral grade7, BP9, glucose10, onset-to needle time11
• Decision tree pruned using cost-complexity parameter to minimize over fitting
<75 years ≥75 years P valueNumber of subjects 60 57 Age (years) 62.6±10.5 82.6±5.2 Male 32 (53%) 31 (54%) Premorbid mRS 0 (0) 0 (0) 0.2Baseline NIHSS 14 (11.5) 14 (11.5) 0.2ASPECTS 10 (0) 10 (0) 0.6Collateral score 1(2) 1 (2) 0.08Systolic BP (mmHg) 150±25 144±23 0.18Diastolic BP (mmHg) 85±15 79±13 0.02Baseline blood glucose 7.1±2.7 6.9±1.8 0.5Aspirin use 17 (28%) 26 (45%) 0.06Anticoagulant use 7 (12%) 6 (10%) 1.0Hypertension 32(53%) 36 (63%) 0.3Diabetes 12 (20%) 7 (12%) 0.3Hyperlipidaemia 17 (28%) 16 (28%) 1.0Smoking history 24 (40%) 8 (14%) 0.002Atrial fibrillation 19 (32%) 15 (26%) 0.5Heart failure 1 (2%) 4 (7%) 0.2Previous stroke 6 (10%) 7 (12%) 0.8Time to treatment min 184 ±69 174±60 0.4
Baseline characteristics
<75 years ≥75 years P value24 h NIHSS 5 (11) 4 (8.5) 0.6sICH 5 (8%) 10 (17%) 0.2Discharge mRS<2 14 (23%) 12 (21%) 0.890 day mRS<2† † 29 (48%) 18 (32%) 0.0690 day mortality‡ 6 (10%) 17 (30%) 0.01
Outcome of IV thrombolysis
† unadjusted OR 0.49, 95% CI 0.23-1.04‡ unadjusted OR 3.82, 95% CI 1.38-10.57
Classification tree for the outcome mRS at 90 days
Classification tree forcing the first split at age 75 years
Conclusion
CART analysis based on standard baseline clinico-radiological characteristics identifies a number of prognostically disparate subgroups of patients following IV thrombolysis
Strengths and weaknesses• CART analysis identified dominant predictors , patterns of
interactions, and subsets where a given variable was of greatest importance
• Able to develop decision rules that can assist clinical decision-making
• Single centre study, sample size, potential bias towards selecting older patients with better premorbid functional status, loss to follow up
References 1. Sandercock P, Wardlaw JM, Lindley RI,, 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(9834): 2352-63
2. Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. 2012; 379(9834): 2364-72
3. Long WJ, Griffith JL, Selker HP, D'Agostino RB. A comparison of logistic regression to decision-tree induction in a medical domain. Comput Biomed Res. 1993;26:74-97
4. Strobl C, Malley J, Tutz G. An introduction to recursive partitioning: rationale, application, and characteristics of classification and regression trees, bagging, and random forests. Psychol Methods. 2009;14(4):323-48
5. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2013; 44:870-947
6. Demchuk AM, Coutts SB. Alberta Stroke Program Early CT Score in acute stroke triage. Neuroimaging Clin N Am. 2005; 15: 409-19
7. Tan IY, Demchuk AM, Hopyan J, et al. CT angiography clot burden score and collateral score: correlation with clinical and radiologic outcomes in acute middle cerebral artery infarct. Am J Neuroradiol. 2009;30:525-31
8. Adams HP Jr, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999; 53: 126–31
9. Ahmed N, Wahlgren N, Brainin M, et al. Relationship of blood pressure, antihypertensive therapy, and outcome in ischemic stroke treated with intravenous thrombolysis: retrospective analysis from Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR). Stroke 2009; 40: 2442–9
10. Poppe AY, Majumdar SR, Jeerakathil T, Ghali W, Buchan AM, Hill MD. Admission hyperglycemia predicts a worse outcome in stroke patients treated with intravenous thrombolysis. Diabetes Care 2009; 32: 617–22
11. Lees KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375:1695-703