Limiti e benefici dei NAO nel binomio
cardiopatia ischemica e FANV
Maddalena Lettino
Humanitas Research Hospital, Rozzano (MI)
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
April 2012
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
EPIDEMIOLOGY
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
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
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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
Incidence rate
per 1,000 person-years
13
maggio 2014
Adjusted
hazard
ratio
(95% CI)
Pradaxa®
Warfarin
(dabigatran)
Ischemic stroke
11.3
13.9
0.80 (0.67-0.96)
134000 pazienti Medicare, di eta’ ≥
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
65
aa,
selezionati
tra
i
nuovi
Major GI bleeding
34.2
26.5
1.28 (1.14-1.44)
utilizzatori
di dabigatran
o di 0.92
Warfarin
Acute MI
15.7
16.9
(0.78-1.08)
per
FANV negli
Mortality
32.6 aa 2010-2012
37.8
0.86 (0.77-0.96)
http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm
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
Stroke/embolism
Non-inferiority
margin = 1.46
No antiplatelet
All stroke
Haemorrhagic
Antiplatelet
Ischaemic
CV death
Major bleed
Minor bleed
All bleed
Intracranial
Extracranial
0.1
0.2
0.5
Dabigatran better
BID = twice daily; CV = cardiovascular
Dans AL et al. Circulation 2013
1.0
2.0
Warfarin better
5.0
10.0
Concomitant antiplatelet therapy subgroup
analysis: major bleeding
Rates of major bleeding increased with concomitant treatment in all
treatment arms
Dabigatran
110 mg BID
Dabigatran
150 mg BID
Warfarin
No antiplatelets
2.2
2.6
2.8
Plus antiplatelets
3.9
4.4
4.8
1.5 (1.2–1.9)
1.6 (1.3–2.0)
1.7 (1.3–2.0)
Annual rate, %
HR (95% CI)
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
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
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
Dabigatran
110 mg BID
Dabigatran
150 mg BID
Warfarin
4.72
4.66
5.21
0.77 (0.50–1.21)
0.81 (0.52–1.26)
2.77
3.24
0.81 (0.61–0.94)
0.95 (0.82–1.10)
0.8727
0.5167
Aspirin & clopidogrel
Annual rate, %
RR (95% CI) vs warfarin
No Aspirin & clopidogrel
Annual rate, %
RR (95% CI) vs warfarin
P value for interaction
3.48
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
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
Heidbuchel et al. Europace (2013) 15, 625–651
Feb 2013
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 (22.5)
Pazienti in terapia con AO e SCA: la survey della
European Heart Rhythm Association (EHRA)
STEMI
NSTE-ACS
Potpara TS et al. Europace 2014; 16: 293
WG Thrombosis/ACCA/EHRA/EAPCI
consensus document 2014
Feb 2013
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
Antiaggregante
Limitandone
l’intensita’
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 gastrointestinali e terapia antitrombotica
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
BMJ 10 ottobre 2006
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
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