PHARMACOLOGICAL Stroke Prevention in Atrial Fibrillation STROKE RISK ASSESSMENT SCORES Vs. BLEEDING RISK ASSESSMENT SCORES.

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1 PHARMACOLOGICAL Stroke Prevention in Atrial Fibrillation STROKE RISK ASSESSMENT SCORES Vs. BLEEDING RISK ASSESSMENT SCORES. Hossam Bahy, MD ( ), 19 tools have been identified 11 stroke scores 1 integrating both s 7 Bleeding scores 6 derived from clinical studies derived from clinical studies 5 based on refinement of existing tools or expert consensus generated from patient data and then validated via further studies 1

2 USA 3% (7 million) will increase to 4.0% in 2030 Heidenreich et al. 2011; Roger et al % and increasing [Kirchhof et al. 2007]. 375,800 Australians (205,800 men and 170,000 women) [Australian Institute of Health and Welfare, 2012]. Stroke assessment tools Among persons with AF (non-valvular form), the of stroke is approximately five times higher than that in persons without AF [Benjamin et al. 1994; Roger et al. 2012; Wolf et al. 1991] 2

3 Percentage of strokes attributable to AF increases dramatically from 1 in 67 persons in the year age group to 1 in 4 for persons in the year age group. [Roger et al. 2012]. Aging is a strong factor for stroke AF is most prevalent in elderly Stroke 3

4 Warfarin (anticoagulant) reduces the of stroke by approximately 60%, while aspirin (antiplatelet) is less effective, reducing the by about one-fifth. [Hart et al. 2007; van Walraven et al. 2002] Stroke schema Atrial Fibrillation Investigators (1994) Laupacis et al Age <65 years with no high- factors Age years with no high- factors - Any age with HTN, DM, previous stroke/tia - age >75 years with or without factors 4

5 Stroke schema Stroke Prevention in Atrial Fibrillation Investigators (SPAF) (1995) No high- or moderate features HTN, no high- features Previous thromboembolism, systolic BP >160 mmhg, LV dysfunction, Women >75 years Recent (3 months) clinical congestive heart failure or left ventricular fractional shortening 25% by M-mode echocardiography. Stroke schema European Atrial Fibrillation Trial Study Group (EAFT) 1995Van Latum et al No factors 1 2 factors 3 factors Risk factors: Previous stroke/tia, ischaemic heart disease, systolic BP >160 mmhg, duration of AF >1 year, 1 infarcts on brain CT, cardiothoracic ratio enlargement on chest roentgenogram. 5

6 Stroke schema Atrial Fibrillation Investigators (1998) Atrial Fibrillation Investigators, 1998 Age <65 y, no clinical factors,, normal LV (normal or mild LV dysfunction) Age y, no clinical factors factors, normal LV - Age >75 y - Age 75 with either clinical factors or abnormal LV. - Age 75 and 1 clinical factors with or without abnormal LV Clinical Risk factors: Previous stroke/tia, history of HTN, and DM. Abnormal LV: Moderate-to-severe systolic dysfunction by 2D echocardiography. Stroke schema Stroke Prevention in Atrial Fibrillation Investigators (1999) Hart et al No high or moderate features - No high- features. - Either of HTN, DM - Women >75 years old. - Men >75 years old +HTN. - Systolic BP >160 mmhg High- features: women >75 years old, men >75 years old + HTN, systolic BP >160 mmhg (any age). Moderate features: HTN (age 75), DM. 6

7 Stroke schema CHADS2(2001)G age et al Score 0 Score 1 2 Score Ischemic stroke. Risk factors: congestive heart failure, HTN, age 75 years, DM 1 point each; previous stroke/tia 2 points. Stroke schema Framingham Heart Study (2003) Wang et al Score 0 7 Score 8 15 Score stroke excludes TIA. Age (0 10 points; years, 0 point; years, 1 points; years, 2 points; years, 3 points; years, 4 points; years, 5 points; years, 6 points; years, 7points; years, 8 points, years, 9 points; >93 years, 10 points), gender (6 points for women), systolic BP (<120 mmhg, 0 point; mmhg, 1 point; mmhg, 2 points; mmhg, 3 points; >179 mmhg, 4 points), DM (5 points), previous stroke/tia (6 points). 7

8 Stroke schema Birmingham/NI CE (UK) (2006) Lip et al Age <65 years with no moderate- or high- features Age 65 years, no high features; age <75 years with DM, HTN, or vascular disease Previous stroke, TIA or thromboembolism ; age 75 years with DM, HTN or vascular disease; HF or abnormal LV function by echocardiography 0.64 Ischemic stroke. Stroke schema Modified CHADS2 score (2008) Rietbrock et al Score 0 Score 1 5 Score > All kinds of stroke. Age years, 1 point; years, 2 points; years, 3 points; years, 4 points; years, 5 points; years, 6 points; female, 1 point; DM, 1 point; history of stroke /TIA, 6 points. 8

9 Stroke schema CHA2DS2-VASc (2010) Lip et al. 2010b Score 0 Score = 1 Score Ischemic stroke, peripheral embolism / pulmonary embolism. Major factors are age 75 years and previous stroke/tia/thromboembolism (2 points each). Clinically relevant non major factors are heart failure, hypertension, diabetes, age years, female gender and vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), 1 point each. Stroke schema ACC/AHA/ESC Guidelines updated (2011) Fuster et al No factors One moderate factor (age 75 years, HTN, HF, LV ejection fraction 35% or less, DM) C- statistic Any high- factor (previous stroke, TIA or embolism, mitral stenosis, prosthetic heart valve) or more than 1 moderate- factor Less well-validated factors are female sex, coronary artery disease and age years. It is unclear whether patient with 1 of these should be categorized as moderate. HTN, hypertension; DM, diabetes mellitus; LV, left ventricle; TIA, transient ischaemic attack; HF, heart failure; BP, blood pressure. 9

10 Most frequently mentioned inputs across all of the stroke tools Previous stroke/tia (11 out of 11) Age (10 out of 11) Hypertension (10 out of 11) Diabetes Mellitus (9 out of 11) Heart failure (5 out of 11) Left ventricular systolic dysfunction (4 out of 11) Female gender (4 out of 11) Other factors incorporated into some tools Coronary heart disease Myocardial infarction Peripheral vascular disease Aortic plaque 10

11 CHA2DS2-VASc Overall, CHA2DS2-VASc has been reported to have a better predictor than the AFI (1994, 1998), SPAF (1995), CHADS2 modified, CHADS2, Framingham (2003), and NICE (2006) tools in AF patients [Lip et al. 2010a; Van Staa et al. 2011]. Figure 1. Proportions categorized as low, moderate, and high for thromboembolism in relation to stroke stratification schema. Gregory Y.H. Lip et al. Stroke. 2010;41: Copyright American Heart Association, Inc. All rights reserved. 11

12 Bleeding assessment tools Altogether, 7 bleeding tools have been developed and employed in evaluating bleeding among AF patients Not all have been specifically developed for patients with AF. All of these bleeding tools stratify patients into low, intermediate, or high bleeding categories Bleeding schema Bleeding Risk Schema Study OBRI Outpatient Bleeding Risk Index Beyth et al. 1998] Intermediat e Age 65 years, GI bleeding in last 2 weeks, previous stroke, comorbidities ( 1 of the following: recent MI, hematocrit <30%, diabetes mellitus or creatinine >1.5 mg/dl),1 point for each above factor. Modification of bleeding index developed by Landefeld and Goldman [Landefeld and Goldman, 1989]) 12

13 Bleeding schema Bleeding Risk Kuijer and colleagues (1999) [Kuijer et al. 1999] 0 >0 and < Age 60 years old (1.6 point), female sex (1.3 point), malignancy (2.2 point) Bleeding schema Bleeding Risk HEMORR2HAGES (2006) Gage et al. 2006] Hepatic and/or renal disease, ethanol abuse, malignancy, older (age >75 years), low platelet count or function, re-bleeding, uncontrolled hypertension, anaemia, genetic factor(s), excessive fall and stroke (1 point for each factor, 2 points for previous bleeding) 13

14 Bleeding schema Bleeding Risk Shiremand and colleagues (2006) Shireman et al. 2006] 1.07 > 1.07 and < Risk score = (0.49 aged >70 years) + (0.32 female) + (0.58 remote bleed) + (0.62 recent bleed) + (0.71 alcohol/drug abuse) + (0.27 diabetes) + (0.86 anaemia) + (0.32 antiplatelet drug use), 1 point for each existing condition, 0 if absent Bleeding schema Bleeding Risk RIETE scheme Ruíz- Giménez et al. 2008] > 4 N/A Recent major bleeding (<15 days prior to thrombotic event) (2 points), creatinine > 1.2 mg/dl (1.5 points), anaemia (1.5 points), malignancy (1 point), clinically overt pulmonary embolism (1 point), age > 75 years (1 point) 14

15 Bleeding schema Bleeding Risk HAS-BLED (2010) Pisters et al. 2010] Hypertension (systolic blood pressure >160 mmhg), abnormal renal (presence of chronic dialysis or renal transplantation or serum creatinine 200 μmol/l), abnormal liver function (chronic hepatic disease [cirrhosis] or bilirubin >2 upper limit of normal, AST/ALT/ALP >3 upper limit of normal), stroke, previous bleeding history or bleeding diathesis or anaemia, labile INRs (high INRs and poor time in therapeutic range), elderly (e.g., age >65 years), drugs (concomitant use of antiplatelet agents or NSAID), alcohol, 1 point each factor Bleeding schema Bleeding Risk ATRIA (2011) Fang et al. 2011] Anaemia (3 points), severe renal disease (e.g., glomerular filtration rate < 30 ml/min or dialysis dependent, 3 points), age 75 years (2 points), prior bleeding (1 point), and hypertension (1 point) 15

16 Both Stroke and Bleeding CARAT Computerized Antithrombotic Risk Assessment Tool [CARAT]) integrates both stroke and bleeding, and specifically considers other key factors in decisionmaking regarding antithrombotic therapy, particularly those increasing the of medication misadventure with treatment (e.g. function, drug interactions, medication adherence) Class I In patients with AF, antithrombotic therapy should be individualized based on shared decision making after discussion of the absolute and relative s of stroke and bleeding and the patient s 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation 16

17 Thanks 17

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