TERAPIA ANTICOAGULANTE NELLA FA: INDICAZIONI E LIMITI. IL PUNTO DI VISTA DEL CARDIOLOGO.

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1 TERAPIA ANTICOAGULANTE NELLA FA: INDICAZIONI E LIMITI. IL PUNTO DI VISTA DEL CARDIOLOGO. Milano, 21 Ottobre 2016 Letizia Riva, MD, PhD Unità Operativa Cardiologia Ospedale Maggiore, Bologna

2 Disclosures Research: Dabigatran, Rivaroxaban, Apixaban, Edoxaban Advisory Boards of Dabigatran, Rivaroxaban, Apixaban, Edoxaban Consulting fees/honoraria: Boehringer Ingelheim, Bayer Healthcare, Daiichi- Sankyo

3 AF is estimated to increase the risk of ischemic stroke by 4-5 fold 10-24% of all strokes are attribuitable to AF among patients aged years all patterns of AF (paroxysmal, persistent and permanent) carry substantial risk of stroke and require consideration for stroke prophylaxis Wolf PA et al. Stroke: a Journal of Cerebral Circulation 1991;2:

4 VKAs have been used for oral anticoagulation for more than 50 years well-controlled warfarin is associated with a 64% reduction in the incidence of stroke and a 26% relative-risk reduction in all-cause mortality maximum benefit and minimum risk from oral VKAs occurs when TTR exceeds 70% Hart RG et al. Ann Intern Med 2007;146: Morgan CL et al. Thrombosis Res 2009;124:37-41

5 ESC 2016 Guidelines: Stroke Prevention in Atrial Fibrillation Mechanical heart valves or moderate or severe mitral stenosis No Estimate stroke risk based on number of Yes CHA 2 DS 2 -VASc risk factors 0 a 1 2 No antiplatelet or anticoagulant treatment (IIIB) OAC should be considered (IIaB) Oral anticoagulation indicated Assess for contra-indications Correct reversible bleeding risk factors a Includes women without other stroke risk factors. b IIaB for women with only one additional stroke risk factor. c IB for patients with mechanical heart valves or mitral stenosis. LAA occluding devices may be considered in patients with clear contraindications for OAC (IIbC) NOAC: (IA) b VKA (IA) b,c Kirchhof P et al. Europace 2016 August 27

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8 G Ital Cardiol 2014;15:123-25

9 Int J Cardiol 2013;167:

10 A T A F Antithrombotic Treatments in non-valvular AF (4.845 pts) OAC Other ATT None Di Pasquale G et al. Int J Cardiol 2013;167:

11 A T A F Total (7148 pts) 7.1% Antithrombotic Treatment by Age 34.1% 58.8% 75 years (3085 pts) 8.4% OAC Other ATT None 25.5% 66.2% p<.0001 Di Pasquale G et al. Int J Cardiol 2013;167:

12 A T A F Prescription of OAC by CHA 2 DS 2 -VASc p=0.012 (non valvular AF, 4845 pts) CHA 2 DS 2 -VASc Di Pasquale G et al. Int J Cardiol 2013;167:

13 Prevalenza della TAO in Registri Italiani Contemporanei % CARD 55.5 Totale 64.2 CARD MED MMG Post dimissione Database HSD PREFER in AF (N=1888) ATA AF FA non valvolare (N=7148) ISAF (N=6036) ARNO (N=2605) Di Pasquale G et al. G Ital Cardiol 2014;15: OSMED FA ad alto rischio di ictus (N=9204)

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16 Br Med J 2001;323:1-7

17 G Ital Cardiol 2014;15:37-43

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19 Limiti della terapia con antagonisti della Vitamina K Risposta non prevedibile Finestra di trattamento stretta (INR range ) Monitoraggio routinario dei fattori della coagulazione Lente insorgenza / termine d azione La terapia con antagonisti della Vitamina K presenta diversi limiti che ne rendono difficoltoso l impiego nella pratica clinica Frequenti aggiustamenti della dose Numerose interazioni alimentari Numerose interazioni con altri farmaci Resistenza al warfarin 1. Chest 2008;133;160S-198S; 2. J Interv Card Electrophysiol 2008; 22: ; 3. Cardiol Clin 2008; 26:

20 VKA Therapeutic Window Efficacy and Safety of Warfarin 20 Odds Ratio Ischemic Stroke Intracranial bleeding International Normalized Ratio Fang MC et al. Ann Intern Med 2004;141:745 ; Hylek EM et al. N Engl J Med 1996;335:540

21 Lancet 2007;370: CHEST 2014;146:

22 patients with AF who started treatment with warfarin rate of hemorrhage = 3.8% per person-year risk of major hemorrhage highest during the first 30 days of treatment with rate of hemorrhage = 11.8% per person-year over 5-year f-up, 8.7% patients visited the hospital for hemorrhage: of these patients, 18.1% died in hospital or within 7 days of being discharged These rates are considerably higher than the rates of 1%-3% reported in RCTs of warfarin therapy CMAJ 2013;185(2): E121-E127

23 Emorragie intracraniche da farmaci antagonisti della Vitamina K 0.3%-1.0% incidenza annuale di emorragie intracraniche in pazienti con fibrillazione atriale trattati con AVK in studi clinici Semin Neurol 2010; 30(5): % di tutte le emorragie intracraniche primarie sono associate a trattamento anticoagulante orale Semin Neurol 2010; 30(5): %-90% delle emorragie intracraniche si verificano con AVK in range INR tra 2.0 e 3.0 International Journal of Emergency Medicine 2011, 4:40 46%-68% mortalità associata ad emorragie intracraniche in pazienti trattati con anticoagulanti orali Stroke 1995; 26:

24 November 19, 2013

25 Weitz JI et al. Am Soc Hematol Educ Program 2012;2012:

26 Stroke or systemic embolic events Lancet 2014;383:

27 Major bleeding Lancet 2014;383:

28 Secondary efficacy and safety outcomes Lancet 2014;383:

29 Secondary efficacy and safety outcomes Lancet 2014;383:

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31 Recommendations for stroke prevention in patients with AF Recommendations Class Level Oral anticoagulation therapy to prevent thromboembolism is recommended for all male AF patients with a CHA 2 DS 2 -VASc score of 2 or more. Oral anticoagulation therapy to prevent thromboembolism is recommended in all female AF patients with a CHA 2 DS 2 -VASc score of 3 or more. Oral anticoagulation therapy to prevent thromboembolism should be considered in male AF patients with a CHA 2 DS 2 -VASc score of 1, considering individual characteristics and patient preferences. I I IIa A A B Oral anticoagulation therapy to prevent thromboembolism should be considered in female AF patients with a CHA 2 DS 2 -VASc score of 2, considering individual characteristics and patient preferences. IIa B Vitamin K antagonist therapy (INR or higher) is recommended for stroke prevention in AF patients with moderate-to-severe mitral stenosis or mechanical heart valves. I B When oral anticoagulation is initiated in a patient with AF who is eligible for a NOAC (apixaban, dabigatran, edoxaban, or rivaroxaban), a NOAC is recommended in preference to a Vitamin K antagonist. I A When patients are treated with a vitamin K antagonist, time in therapeutic range (TTR) should be kept as high as possible and closely monitored. I A AF patients already on treatment with a vitamin K antagonist may be considered for NOAC treatment if TTR is not well controlled despite good adherence, or if patient preference without contra-indications to NOAC (e.g. prosthetic valve). IIb A Kirchhof P et al. Europace 2016 August 27

32 Pazienti warfarin-naïve I NAO sono da preferire al warfarin in presenza di: difficoltà logistiche nell effettuare il monitoraggio della TAO non disponibilità ad effettuare il monitoraggio dell INR pregresso ictus ischemico pregressa emorragia intracranica paziente candidato a cardioversione elettrica

33 Pazienti warfarin-experienced Proponibile lo switch ai NAO in caso di: pregresso stroke / TIA in corso di warfarin con INR in range terapeutico pregressa emorragia cerebrale in corso di warfarin con INR in range terapeutico pregressa emorragia maggiore (escluse le emorragie gastrointestinali) difficoltà logistiche nell effettuare il monitoraggio della TAO impiego giornaliero di basse dosi di warfarin (8-10 mg/settimana) labilità dell INR qualità subottimale della TAO (TTR < 60%) farmaci concomitanti interferenti con il warfarin e non interferenti con i NAO

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