1. 1 Dr. Mario Fitz Maurice Electrofisiología Cardíaca Hospital Rivadavia mdfitzmaurice@gmail.com AF AC Anticoagulation in Atrial Fibrillation

2. 2 65.084 con ≥ 70 años y FA 813.546 con 70 años o más Población: 40.677.348 (Julio 2008 estimado) Prevalence of AF increases with age Population: 40,677,348 (estimation July 2008) 813,546 with 70 years of age or more 65,084 with > 70 years of age and AF

3. 3 THE EPIDEMIC Due to the aging of population, this figure is expected to duplicate in 30 years.. Go AS, et al. JAMA 2001;285:2370-2375. In 2007, AF was diagnosed in 6.3 million people from USA

4. 4 AF increases the risk of stroke AF relates with prothrombotic states 1 Risk ~5 times greater for stroke 1 In USA one stroke occurs per minute A cardioembolic stroke is associated to a 25% mortality at 30 days 4 Stroke related to AF has a ~50% mortality after 1 year 5 Up to 3 million people suffer stroke associated to AF each year all over the world 1-3 Effect of 1st ischemic stroke in patients with AF Disabling

5. 5 Evidence in anticoagulation

6. 6 SPAF 1 Stroke Prevention in Atrial FibrillationSPAF 1 Stroke Prevention in Atrial Fibrillation BAATAF 2 Boston Area Anticoagulation Trial for Atrial FibrillationBAATAF 2 Boston Area Anticoagulation Trial for Atrial Fibrillation CAFA 3 Canadian Atrial Fibrillation AnticoagulationCAFA 3 Canadian Atrial Fibrillation Anticoagulation AFASAK 4 Copenhagen InvestigatorsAFASAK 4 Copenhagen Investigators SPINAF 5 Stroke Prevention in Nonrheumatic Atrial FibrillationSPINAF 5 Stroke Prevention in Nonrheumatic Atrial Fibrillation Clinical studies on AF 1 Circulation. 1991;84:527-539. 2 N Engl J Med. 1990;323:1505-1511 3 J Am Coll Cardiol. 1991;18:349-355 4 The Lancet. 1989;1:175-178 5 N Eng J Med. 1992;327:1406-1412 AFASAK SPAF IIISPINAFBAATAFSPAF IISPAF IBAFTA ACTIVE W EAFTSPORTIF AC vs PLACEBO SAFETY IN ELDERLY PEOPLE INR RANGE

7. 7 67% of general reduction of stroke StrokeDeath

8. 8 SPAF Investigators. Lancet. 1996;348:633-638. Terapia combinada mejor Dosis-ajustada warfarina mejor Stroke, IAM o muerte vascular Evento primario o muerte vascular Todos stroke incap Stroke isquémico incapacitante Evento primario 0 0.5 1 1.5 2 Riesgo Relativo e IC 95% (barra horizontal) Hemorragia mayor Events: Relative risk, adjusted dose vs combination therapy SPAF III Adjusted dose Warfarin better Combination therapy Better Primary event Disabling ischemic stroke All disabling strokes Primary event or vascular death Stroke, AMI, or CV death Mejor bleeding

9. 9 Duda en ancianos BAFTA Mant J. Lancet 2007;370:493-503.

10. 10 Anticoagulation in people older than 75 years old BAFTA – Birmingham Atrial Fibrillation Treatment of the Aged Patients with AF ≥ 75 years old (median 81,5 ± 4,2 years) Randomization 1:1 Warfarin (INR 2-3) versus Aspirin 75 mg/day F/U: 2.7 years EP 1°: Disabling stroke or arterial embolism Major bleeding Extracranial major bleeding RR:0.48 (0.28-0.80) p=0.003 NNT:50 ns Events per year (%) Warfarin (n=488) Aspirin (n=485) n=973 RRR>50% P=0.002 All strokes 1 Mant J. Lancet 2007;370:493-503.

11. 11 So, ¿Why a new therapeutic armory? Unpredictable response Narrow therapeutic window (INR 2-3) Systematic monitoring of coagulation Slow start and disappearance of effect Frequent dose adjustment Numerous interactions with food Numerous interactions with other drugs Resistance to warfarin

12. 12 Sites of action, new anticoagulants

13. 13 Nuevas Drogas En fa Dabigatran Apixaban Rivaroxaban Clopidogrel Edoxaban In patients with AC contraindicated

14. 14 In the presence of contraindications for AC With severe adverse effects of hepatotoxicity NNT=26.3 RR 64% Warfarin not blind, GI Bleeding, AMI, two doses, costs, most CHADS 1 NNT=178 RR 36% Meta-analysis of ischemic stroke or systemic embolism Category W vs placebo W vs W in low doses W vs ASA W vs ASA + clopidogrel W vs ximelagatran W vs dabigatran 150 In favor of warfarin In favor of another treatment

15. 15 Dabigatran Warfarin Acenocumarol Evidence/ Years of use Cost/Benefit/Evidence Warfarin Direct inhibitors $$

16. 16 AFASAK SPAF IIISPINAFSPAF IISPAF IBAFTAEAFTSPORTIF But while the race continues...

17. 17 Waldo AL. J Am Coll Cardiol 2005;46:1729-1736. AC in the real world Underuse of AC regardless of risk No treatment ASA Warfarin + ASA Warfarin AllLow risk Moderate risk High risk

18. 18 ACO: Chronic anticoagulation n = 407 (48,5%) n = 288 (34,3%) n = 152 (18,1%) n = 135 (16,1%) N = 840 Labadet C y col. Reg RAC 2000 AC, Real world Treatments used to prevent thromboembolism

19. 19 Average= 50% without AC Management of AF in clinical practice: Indication of K vitamin antagonists No anticoagulation K vitamin antagonists Medicare cohort, USA ATRIA cohort (managed care system, California, USA)

20. 20 13 Community Hospitals 21 Academic Hospitals Nearly half of patients with AF and high risk received anticoagulation therapy Waldo et al. JACC 2005; 46(9): 1729-1736 AC: Real world Underused in AF

21. 21 Stroke reduction >80% Stroke reduction 67% INR control: Clinical studies vs clinical practice INR control in clinical studies vs clinical practice (TTR*) *TTR = Time in Therapeutic Range (INR 2.0-3.0) Clinical study 1 Clinical practice 2 % of patients eligible that receive warfarin

22. 22 AGE YEARS 69 - 79 80 - 89> 89 70 - 7980 - 8960 - 69 Patients w/o AC STROKES PER 1000 PTS/YEAR The risk of stroke is increased dramatically with age Use of AC However the use of AC IS DECREASING In summary... 100 80 60 40 20 0

23. 23 Cohort in community, Olmsted County, Minnesota n=270 PSAF: Persistent AF PXAF: Paroxysmal AF PAF: Permanent AF Keating RJ. Am J Cardiol 2005;96:1420 –1424. Cohort in community, Stockholm n=2824 Paroxysmal AF Prognostic impact DEATH Friberg L. Eur Heart J 2007;28:2346-2353. PSAF: Persistent AF PXAF: Paroxysmal AF PAF: Permanent AF

24. 24 Paroxysmal AF Prognostic impact DEATH Mortality according to CHADS Rate of standardized mortality (“how higher is risk than the general population”) Friberg L. Eur Heart J 2007;28:2346-2353. Cause of deathRMS95% CI Cardiovascular2.11.6 – 2.6 Myocardial infarction2.41.4 – 3.7 Ischemic disease2.61.7 – 3.4 Heart failure2.61.3 – 5.2

25. 25 Paroxysmal AF Prognostic impact Stroke Incidence of stroke Events/1000 patients/year Paroxysmal AF Permanent AF No details 1 Friberg L. Eur Heart J 2009;doi:10.1093. 2 Wang TJ. JAMA 2003;290:1049-1056. 3 Hart RG. J Am Coll Cardiol 2000;35:183-187. RMS95% CI Ischemic stroke2.121.5 – 2.7 ≤ 75 y.o.2.271.3 – 3.8  75 y.o. 2.051.3 – 2.8 Men1.981.1 – 2.8 Women2.241.4 – 3.1 Rate of standardized ischemic stroke incidence

26. 26 (2) Friberg L. Eur Heart J 2009;doi:10.1093. (1) Waldo AL. J Am Coll Cardiol 2005;46:1729-1736. P  0.001 % of AC FAPX AC in the real world The risk of stroke is the same in patients with AF, without taking into account whether AF is paroxysmal or sustained

27. 27 NOT TO LOSE THE RACE AF AC CHA2DS2VASc Antecedentes de Stroke 2 Edad > 75 años 2 HTA 1 DBT 1 Insuficiencia Cardíaca 1 Antec, Vascular 1 Edad >65<75 1 Sexo femenino 1 Alto Riesgo >4 Moderado Riesgo 2-3 Bajo Riesgo 0-1 History of stroke Age >75 y.o. HTN Diabetes Heart failure History of CV disease Age >65<75 Female gender High risk>4 Moderate risk2-3 Low risk0-1 1

28. 28 AF Dr. Mario Fitz Maurice THANK YOU VERY MUCH FOR YOUR ATTENTION Rhythm control Rate control, but without forgetting INR CONTROL