Fibrillazione atriale e rischio di stroke nell anziano

Fibrillazione atriale e rischio di stroke nell anziano Niccolò Marchionni Cattedra di Geriatria, Università di Firenze SOD Cardiologia e Medicina Geriatrica AOU Careggi, Firenze Società Italiana di Gerontologia e Geriatria

Incidenza di FA per età Incidenza (per 1000 anni persona) 60 40 20 0 30 Miyasaka Y. Circulation, 2006 40 50 60 70 80 90 100 Età (anni)

Schnabel RB et al, Lancet 2009 Age (years) 45-49 -3 1 PR (ms) <160 0 50-54 -2 2 160 199 1 55-59 0 3 >200 2 60-64 1 4 Age / Cardiac murmur 45-54 5 65-69 3 5 55-64 4 70-74 4 6 65-74 2 75-79 6 7 75-84 1 80-84 7 7 >85 0 >85 8 8 Age / HF 45-54 10 BMI (Kg/m 2 ) <30 0 55-64 6 >30 1 65-74 2 >75-84 0 SBP (mmhg) <160 0 Tx Hypertension No 0 >160 1 Yes 1 Women / Men; Age / Cardiac murmur: Age at which significant cardiac murmur developed; Age / HF: Age of heart failure

Predicted 10 year risk of atrial fibrillation 10 year risk (%) 30 20 10 0 < 1 Participants N = 4764; Women: 55% Age: 45 95 years A Fib (10 years): N= 457 (10%) 2 2 3 4 6 0 1 2 3 4 5 6 7 8 9 >10 Risk Score 8 12 16 22 > 30 Schnabel RB et al, Lancet 2009

Atrial Fibrillation and Cardioembolic syndromes Cerebral Cardio embolism (85%)* Peripheral Cardio embolism (15%) * Coronary (MI) Visceral (Mesenteric, Renal, etc.) Limbs * Cabin Am J Cardiol 1990

Cerebrovascular Disease: Stroke Subtype Hemorrhagic stroke (17%) Intracerebral hemorrhage (59%) Ischemic stroke (83%) Lacunar small vessel disease (25%) Atherothrombotic disease (20 25%) SAH (41%) Embolism (20%) Cryptogenic (30%) Albers GW et al. Chest. 1998;114:683S 698S. Rosamond WD et al. Stroke. 1999;30:736 743.

CE/AF Stroke rate (N/100.000/year) 240 200 160 120 80 40 0 Men Women 0 0 0 1 4 2 28 12 108 Age (years) 73 227 216 <40 40-50 50-60 60-70 70-80 >80 Bejot Y, 2009 CE/AF stroke = 572/3064 (18.7%) CE/AF 80.6 vs. other strokes 73.6 years

AF monitoring after cryptogenetic stroke 30 25 Pts. with AF detected (%) 20 15 10 6,8 11,8 17,5 5 2,7 0 1 ECG Multiple ECGs 24 h Holter 7 d Holter D. Jabaudon. Stroke 2004; 35: 1647 1651

Intermittent AF may account for a large proportion of otherwise cryptogenic stroke A study of 30 day cardiac event monitor Conclusion: The 30 DEM changed the medical treatment of 20% of patients with otherwise cryptogenic stroke because of the detection of intermittent AF despite no detection of AF on electrocardiography and in telemetry monitoring in the majority of patients. Elijovich et al. J of Stroke and Cerebrovascular Diseases 2009

Clinical state at time of maximum impairment among patients with and without AF in a European Concerted Action (7 Countries, first stroke, age: 72 years, N=4462) (%) Atrial Fibrillation Yes (N=803) No (N=3659) 18.0% Confusion 39.0 27.6 <0.001 Coma 12.3 7.6 <0.001 Paralysis 51.4 36.6 <0.001 Aphasia 41.8 30.3 <0.001 Disarthria 35.0 33.2 NS Swallowing problems 40.3 23.6 <0.001 Urinary incontinence 54.6 38.7 <0.001 P Lamassa M, 2001

AF Age: 77** yrs, Women: 58%** No AF Age: 71 yrs, Women: 48% Lamassa M, 2001 40 p<0.0001 p<0.0001 80 p<0.0001 P=0.003 P=NS Mortality (%) 30 20 10 0 19 12,7 In-Hospital 32,8 19,9 3-Month Destination at discharge (%) 60 40 20 0 71 61 Home 9 10 6 9 Institution Rehab Tx **: p<0.001 vs the same category of No AF pts

AF (N=470) No AF (N=1992) Lacunar infarct** 16 Posterior circulation infarct 15.5 33.8 Total anterior circulation infarct** Lacunar infarct 29.2 Total anterior circulation infarct 25.1 34.7 Partial anterior circulation infarct* Posterior circulation infarct 17 28.7 Partial anterior circulation infarct *: p<0.05 vs the same category of No AF pts **: p<0.001 vs the same category of No AF pts Lamassa M, 2001

Rischio di recidive a due anni, per tipo di ictus (n= 531) Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long term survival in ischemic stroke subtypes: a population based study. PL Kolominsky Rabas et al. Stroke. 2001;32:2735 2740

Validation of clinical classification schemes for predicting stroke Results from the National Registry of Atrial Fibrillation CHADS 2 Risk Stratification Scheme Risk Factors Score C recent Congestive heart failure 1 H Hypertension 1 A Age >75 years 1 D Diabetes mellitus 1 S 2 History of Stroke or TIA 2 Gage, JAMA, 2001 Rockson, JACC, 2004

Relationship between CHADS 2 Score and Risk of Stroke Results from the National Registry of Atrial Fibrillation Annual Stroke Rate (%) 20 15 10 5 0 Gage, JAMA, 2001 Rockson, JACC, 2004 Basso 2.8 1.9 Medio 4.0 5.9 8.5 12.5 18.2 0 1 2 3 4 5 6 CHADS 2 Score Elevato

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 Stroke Risk Assessment in AF: the CHA 2 DS 2 VASc Score Lip, Chest, 2010 Stroke Risk Factor Score Congestive Heart Failure / LV Dysfunction 1 Hypertension 1 Age >75 years 2 Diabetes mellitus 1 Stroke / TIA / TE 2 Vascular Disease (MI, PAD, aortic plaque) 1 Age 65-74 years 1 Sex category (female) 1 Maximum score = 9; Score >1 OAC; Score = 1 ASA (75 325 mg) or OAC (preferred); Score = 0 ASA (75 325 mg) or None (preferred)

Go AS et al. Circulation 2009 Thromboembolism Rate (per 100 person years) Study period: July 1996 December 1997 through September 30, 2003 Events N = 676 / 10,908 1.63 2.76 4.22 60 N=7,690 72 yrs 45 59 N=2,499 76 yrs <45 N=1,338 78 yrs Estimated Glomerular Filtration Rate (ml/min/1.73 m 2 ) GFR =186 [serum creatinine (mg/dl)] 1.154 (age) 0.203 (0.742 if female)

Rischio annuale di ictus in pazienti con fibrillazione atriale, per gruppi di età Rischio relativo annuale 8 6 4 2 0 The Atrial Fibrillation Investigators AFI, Arch Int Med, 1994 Gruppi di età (anni) 10 <65 65-75 >75 1 1 4.9 1.7 4.3 1.1 5.7 3.5 1.7 1.7 8.1 No Si No Si No Si Fattori di rischio 1.2 Rockson, JACC, 2004 Fattori di rischio: diabete, ipertensione, storia di ictus/tia Placebo Warfarin

Analisi di Kaplan Meier sulla sopravvivenza a 30 giorni dopo ictus ischemico in 596 pazienti con fibrillazione atriale Probabilità di sopravvivenza Age by treatment None 79 years Aspirin 80 years Warfarin 76 years 2003;349:1019 1026 Giorni

A novel user friendly score (HAS BLED) to assess one year risk of major bleeding in atrial fibrillation patients: the Euro Heart Survey Pisters, Chest, 2010 Bleeding Risk Assessment in AF: HAS BLED Bleeding Risk Score Letter Clinical Characteristic Points H Hypertension 1 A Abnormal Renal / Liver Function 1 S Stroke 2 B Bleeding 1 L Labile INRs 2 E Elderly 1 D Drugs / Alcohol 1 Maximum score = 9; Hypertension Sap >160 mmhg; Drugs antiplatelets agents or NSAIDS Score > 3 High risk patient: Caution and regular review following the initiation of antithrombotic therapy (OAC & ASA)

13.08 Incidenza emorragie maggiori (eventi per 100 anni persona) 10 8 6 4 2 0 Età 80 anni N=153 P=0.009 Età < 80 anni N=319 4.75 N=472 Età=77 (65 97) 0 100 200 300 400 Durata terapia con warfarin (giorni) Circulation, 2007

VKA: stretto range terapeutico 80 Target INR (2.0-3.0) Ictus ischemico Emorragia intracranica Eventi / 1000 pazienti anno 60 40 20 0 <1.5 1.5 1.9 2.0 2.5 2.6 3.0 3.1 3.5 3.6-4.0 4.1-4.5 >4.5 1. Hylek EM, et al. N Eng J Med 2003; 349:1019-1026. International Normalised Ratio (INR)

Incidenza emorragie maggiori (eventi per 100 anni persona) 100 80 60 40 20 0 IRR 4 vs. <4 = 19.34 4,1 3,8 15,8 99,3 <2 2 3 3.1 <4 4 Valori di INR IRR 90 vs. >90 = 3.31 14,2 4,1 90 >90 Inizio terapia (giorni) Circulation, 2007

Annual rate (%/year) 20 10 0 20 10 Control (Ref.) 1 Antipl. Ther. (HR) 0.81 OAC (HR) 0.36 Ischemic Stroke Serious Hemorrhage Vascular Event <65 65 70 70 75 75 80 >80 Trials N=12; Patients N=8932 Control N=1971 Antiplatelet therapy N=3531 Oral anticoagulation N=3430 0 <65 65 70 70 75 75 80 >80 Van Walraven, Stroke, 2009

The Net Clinical Benefit of Warfarin Anticoagulation in Atrial Fibrillation Daniel E. Singer, MD, Yuchiao Chang, PhD, Margaret C. Fang, MD, MPH, Leila H. Borowsky, MPH, Niela K. Pomernacki, RD, Natalia Udaltsova, PhD, and Alan S. Go, MD Massachusetts General Hospital, Boston, Massachussetts, and University of California, San Francisco, San Francisco, and Kaiser Permanente of Northern California, Oakland, California. The ATRIA Cohort of AF pts N = 13559; Age: 73 years Annual Rate Ictus/Embolism Warfarin off : 2.10% vs. Warfarin on : 1.27% ICH Warfarin off : 0.32% vs. Warfarin on : 0.58% Net Clinical Benefit : (annual rate of ischemic strokes / systemic emboli prevented by warfarin) minus (intracranial hemorrhages due to warfarin) * impact weight The impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism Ann Intern Med, 2009

Le raccomandazioni dell American Geriatrics Society sul monitoraggio della terapia anticoagulante nell anziano Dosaggio dei valori di INR: 1. Quotidiano fino al raggiungimento di valori stabili 2. Due tre volte a settimana per i successivi 7 15 giorni 3. Una volta a settimana nel mese successivo 4. Quindi, una volta al mese American Geriatrics Society Clinical Practice Committee J Am Geriatr Soc 2002

Conclusions 1. Physicians may be apprehensive about prescribing OAC to elderly patients, given concerns about a higher risk of hemorrhage. 2. However, age alone should not prevent prescription of OAC in elderly patients, given the potential greater net clinical benefit among such patients. 3. Appropriate stroke and bleeding risk stratification and choice of antithrombotic therapy are essential. 4. Once OAC is initiated, good INR control (at least 65% TTR) and the provision of a health care infrastructure to support such INR therapeutic targets are crucial to prevent warfarin associated complications. JACC, 2010