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  • Maddalena Lettino

    Humanitas Research Hospital, Rozzano (MI)

    Limiti e benefici dei NAO nel binomio cardiopatia ischemica e FANV

  • April 2012

    Disclosure

    Speaker fee: Astra Zeneca, BMS,

    Boehringer, Eli Lilly, Daichii Sankio,

    Bayer, Pfizer

    Advisory board member: Eli Lilly, Astra

    Zeneca, Bayer, Boeheringer, Daiichi

    Sankyo, BMS, Pfizer, Sanofi

  • Overview

    FA e cardiopatia ischemica

    NAO e infarto miocardico acuto

    NAO e associazione con gli antiaggreganti piastrinici

    I documenti di consenso

    Le complicanze emorragiche

  • Overview

    FA e cardiopatia ischemica

    NAO e infarto miocardico acuto

    NAO e associazione con gli antiaggreganti piastrinici

    I documenti di consenso

    Le complicanze emorragiche

  • TROMBOSI ARTERIOSA E VENOSA

  • Approximately 70-80% of all patients in AF have an indication for continuous OAC

    Coronary artery disease co-exists in 20-30% of patients in AF

    5-7% of pts undergoing PCI have AF or other indications

    for OAC

    With an estimated prevalence of AF in 1-2% of the

    European population, one to two million anticoagulated patients are candidate for coronary revascularization, often

    in the form of PCI, usually including stents

    EPIDEMIOLOGY

  • THERAPY

    DAPT has assumend a central role in treatment

    after coronary stent deployment

    OAT might be indicated for stroke prevention in several conditions like AF, mechanical prosthetic

    valves, previous TE and LV thrombosis

    DAPT is less effective in preventing stroke than is

    OAC alone and OAC is insufficient to prevent stent thrombosis

    + +

  • Overview

    FA e cardiopatia ischemica

    NAO e infarto miocardico acuto

    NAO e associazione con gli antiaggreganti piastrinici

    I documenti di consenso

    NAO dopo una SCA?

  • MI, angina instabile, PCI,

    morte improvvisa, morte cardiaca

    Incidenza annuale (%)

    HR vs warfarin (95% CI)

    Dabigatran 110 mg 3.16 0.93 (0.80-1.06, p=0.28)

    Dabigatran 150 mg 3.33 0.98 (0.85-1.12, p= 0.77)

    Warfarin 3.41 nd

  • http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm

    134000 pazienti Medicare, di eta’ ≥ 65 aa, selezionati tra i nuovi

    utilizzatori di dabigatran o di Warfarin per FANV negli aa 2010-2012

    13 maggio 2014Incidence rate per 1,000 person-years

    Adjusted hazard ratio

    (95% CI)

    Pradaxa®

    (dabigatran) Warfarin

    Ischemic stroke 11.3 13.9 0.80 (0.67-0.96)

    Intracranial haemorrhage 3.3 9.6 0.34 (0.26-0.46)

    Major GI bleeding 34.2 26.5 1.28 (1.14-1.44)

    Acute MI 15.7 16.9 0.92 (0.78-1.08)

    Mortality 32.6 37.8 0.86 (0.77-0.96)

  • Overview

    FA e cardiopatia ischemica

    NAO e infarto miocardico acuto

    NAO e associazione con gli antiaggreganti piastrinici

    I documenti di consenso

    Le complicanze emorragiche

  • Concomitant antiplatelet therapy subgroup analysis: rationale

    Many patients with AF (35–40%) have conditions that require concomitant treatment with antiplatelet agents1,2

    In RE-LY®:3,4

    – 17% had a past history of MI

    – 40% were treated with Aspirin at baseline

    – 38% received concomitant Aspirin or clopidogrel

    – Use of other antiplatelet agents was negligible

    Post-hoc analysis:4

    – Compare efficacy and safety of dabigatran vs warfarin in patients with or without antiplatelet therapy

    – Determine effect of concomitant antiplatelet therapy on bleeding rates

    BID = twice daily; MI = myocardial infarction 1. Douketis JD et al. Thromb Res 2011;127:513–7; 2. Johnson SG et al. Chest 2007;131:1500–7; 3. Connolly SJ et al. N Engl J Med 2009; 361:1139–51. 4. Dans AL et al. Circulation 2013

  • Concomitant antiplatelet therapy subgroup analysis: dabigatran 150 mg BID vs warfarin

    BID = twice daily; CV = cardiovascular Dans AL et al. Circulation 2013

    Stroke/embolism

    10.0

    All stroke

    CV death

    Major bleed

    Minor bleed

    All bleed

    1.00.50.20.1 2.0 5.0

    Haemorrhagic

    Ischaemic

    Intracranial

    Extracranial

    Non-inferiority margin = 1.46

    No antiplatelet

    Antiplatelet

    Dabigatran better Warfarin better

  • Concomitant antiplatelet therapy subgroup analysis: major bleeding

    Rates of major bleeding increased with concomitant treatment in all treatment arms

    BID = twice daily; BP = blood pressure; HR = hazard ratio; TIA = transient ischaemic attack

    Dans AL et al. Presented at ESC 2011; Session 709009 – 709010; e-slides available at: http://spo.escardio.org/eslides/view.aspx?eevtid=48&fp=1161; accessed Sept 2011 Disclaimer: Dabigatran etexilate is now approved for clinical use in stroke prevention in atrial fibrillation in certain countries. Please check local prescribing information for further details

    Dabigatran 110 mg BID

    Dabigatran 150 mg BID

    Warfarin

    Annual rate, %

    No antiplatelets 2.2 2.6 2.8

    Plus antiplatelets 3.9 4.4 4.8

    HR (95% CI) 1.5 (1.2–1.9) 1.6 (1.3–2.0) 1.7 (1.3–2.0)

    Adjusted for age, gender, warfarin experience, systolic BP, coronary disease, heart failure, hypertension, diabetes, prior TIA, creatinine clearance, and statin use; results were unaffected by duration of antiplatelet use (

  • Concomitant Aspirin & clopidogrel subgroup analysis: major bleeding

    Separate analysis showed increased risk of major bleeding with concomitant use of antiplatelet therapy, with similar effects seen across treatment groups

    BID = twice daily

    Eikelboom JW et al. Circulation 2011;123:2363–72 Disclaimer: Dabigatran etexilate is now approved for clinical use in stroke prevention in atrial fibrillation in certain countries. Please check local prescribing information for further details

    Dabigatran 110 mg BID

    Dabigatran 150 mg BID

    Warfarin

    Aspirin & clopidogrel

    Annual rate, % 4.72 4.66 5.21

    RR (95% CI) vs warfarin 0.77 (0.50–1.21) 0.81 (0.52–1.26)

    No Aspirin & clopidogrel

    Annual rate, % 2.77 3.24 3.48

    RR (95% CI) vs warfarin 0.81 (0.61–0.94) 0.95 (0.82–1.10)

    P value for interaction 0.8727 0.5167

  • Overview

    FA e cardiopatia ischemica

    NAO e infarto miocardico acuto

    NAO e associazione con gli antiaggreganti piastrinici

    I documenti di consenso

    Le complicanze emorragiche

  • WG Thrombosis/EHRA/EAPCI consensus document 2010

  • Feb 2013

    Heidbuchel et al. Europace (2013) 15, 625–651

  • Documenti di consenso Europa/USA punti di contatto

    Utilizzare una bassa dose di ASA

    Privilegiare le PCI semplici e gli stent metallici

    Utilizzare l’approccio radiale

    Evitare il bridge della TAO

    Mantenere l’INR ai livelli bassi del range terapeutico (2- 2.5)

  • Pazienti in terapia con AO e SCA: la survey della European Heart Rhythm Association (EHRA)

    Potpara TS et al. Europace 2014; 16: 293

    STEMI

    NSTE-ACS

  • Feb 2013

    WG Thrombosis/ACCA/EHRA/EAPCI consensus document 2014

  • Overview

    FA e cardiopatia ischemica

    NAO e infarto miocardico acuto

    NAO e associazione con gli antiaggreganti piastrinici

    I documenti di consenso

    Le complicanze emorragiche

  • Come ridurre la probabilita’ di un sanguinamento maggiore?

    Anticoagulante Limitandone l’intensita’

    Antiaggregante Limitandone la

    durata

    Scelta dello stent e

    dell’accesso vascolare Scelta della procedura

    Protezione gastrica

  • Management of bleeding

    Steg G et al. Eur Heart J 2011

  • Bleeding on antithrombotic therapy: a practical approach

    Modified from Siegal DM et al. Eur Heart J 2013; 34: 489

  • GI tract: major source of bleeding in patients treated with antithrombotic drugs

    Desai J et al Thromb Haemost 2013

  • Associazione tra sanguinamenti gastro- intestinali e terapia antitrombotica

    BMJ 10 ottobre 2006

    Farmaco OR

    ASA 1.8

    Clopidogrel 1.1

    TAO 1.8

    Dipiridamolo 1.9

    ASA+clopidogrel 7.4

    ASA+TAO 5.3

    ASA+dipiridamolo 2.3

  • ESC guidelines UA/NSTEMI 2011

  • In case of gastrointestinal bleeding……

    Desai J et al Thromb Haemost 2013

  • In conclusione

    Non esiste una controindicazione all’impiego dei NAO nei pazienti con patologia aterotrombotica o che si sottopongono a procedure di rivascolarizzazione per via percutanea

    Non e’ stata documentata una interazione sfavorevole in termini di efficacia e sicurezza tra i NOA e gli antiaggreganti; e’ riportato un incremento dei sanguinamenti nell’associare i NOA alla doppia antiaggregazione

    Il parere degli esperti nei documenti di consenso e le linee guida propende per una limitazione all’impiego protratto di una triplice terapia antitrombotica

    No

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