limiti e benefici dei nao nel binomio cardiopatia ... · overview fa e cardiopatia ischemica nao e...
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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
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 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
FA e cardiopatia ischemica
NAO e infarto miocardico acuto
NAO e associazione con gli antiaggreganti piastrinici
I documenti di consenso
Le complicanze emorragiche
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
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?
AnticoagulanteLimitandone l’intensita’
AntiaggreganteLimitandone la
durata
Scelta dello stent e
dell’accesso vascolareScelta della procedura
Protezione gastrica
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
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