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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

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





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






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 infarction1. 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 = cardiovascularDans 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 2011Disclaimer: 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

Dabigatran110 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 (<50% or ≥50% of the trial duration) or number of antiplatelets used

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;123:2363–72Disclaimer: 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

Dabigatran110 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






WG Thrombosis/EHRA/EAPCI consensus document 2010

Feb 2013

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

Documenti di consenso Europa/USApunti 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






Come ridurre la probabilita’ di un sanguinamento maggiore?

AnticoagulanteLimitandone l’intensita’

AntiaggreganteLimitandone la

durata

Scelta dello stent e

dell’accesso vascolareScelta 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 guidelinesUA/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

Non e’ ancora noto l’impatto sulle problematiche trombotiche ed emorragiche di questi pazienti ogni associazione che preveda i nuovi farmaci antipiastrinici o i nuovi anticoagulanti orali

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