Buone regole nel menage à trois della terapia antitrombotica nella

Buone regole nel menage à trois della terapia
antitrombotica nella fibrillazione atriale dopo impianto
di stent.
Andrea Rubboli
Unità Operativa di Cardiologia
Laboratorio di Cardiologia Interventistica
Ospedale Maggiore
Bologna
Safety
(total bleeding)
Efficacy
(stroke, death, MI, re-PCI/CABG,
stent thrombosis)
Dewilde WJW et al. Lancet 2013;381:1107-15
Sicurezza
differenza trascinata da emorragie non maggiori/severe
enorme eccesso di emorragie vs. Letteratura/pianificazione dello studio
disegno “in-aperto”
Efficacia
differenza trascinata da mortalità non-cardiaca
sottodimensionamento per identificare differenze di trombosi di stent
preponderanza (70-75%) di pazienti sottoposti a PCI per CAD stabile
Rubboli A, Limbruno U. G Ital Cardiol 2013;14:564-8
• VKA + ASA + clopidogrel recommended (if stroke risk = moderate-high)
Class
LOE
IIa
C
Lip GY et al. Thromb Haemost 2010;103:13-28
Gao F et al. Circ J 2010;74:701-8
Major bleed
Gao F et al. Int J Cardiol 2011;148:96-101
Rubboli A
Andrade JG et al.
J Geriatr Cardiol 2011;8:2017-14
Can J Cardiol 2012;29:204-12
In-hospital
3.3 ± 1.9
1.59 (95% CI 0.43-4.01)
30-day
5.1 ± 6.7
2.38 (95% CI 0.98-3.77)
6-month
8.0 ± 5.2
4.55 (95% CI 0.56-8.53)
12-month
9.0 ± 8.0
--
Class
LOE
• BMS to be preferred
IIa
C
• DES to be avoided *
IIa
C
* and/or strictly limited to clinical (diabetes) and/or anatomical (long lesions, small vessels, chronic total
occlusion) situations where significant benefit over BMS is expected
Lip GY et al. Thromb Haemost 2010;103:13-28
new-generation (everolimus-/zotarolimus-, polymer-free) DES to be preferred
Rubboli A et al. Chest 2011;139:981-7
Adjusted HR of ST:
n-DES vs o-DES: 0.57 (95% 0.41-0.79)
n-DES vs BMS: 0.38 (95% CI 0.28-0.52)
Sarno G et al. Eur Heart J 2012;33:606-13
Class
LOE
• 3-6 months duration recommended
IIa
C
• throughout triple therapy, careful INR regulation at 2.0-2.5 recommended
IIa
C
Lip GY et al. Thromb Haemost 2010;103:13-28
Rossini R et al. Am J Cardiol 2008;102:1618-23
• gastric protrection (PPI, H2-receptor inhibitors, antacids) to be routinely given
Class
LOE
IIa
C
Lip GY et al. Thromb Haemost 2010;103:13-28
Rubboli A et al. J Cardiovasc Med 2009;10:200-3
Total
(n = 401)
Triple therapy
(n = 339)
OAC + SAPT
(n = 20)
DAPT
(n = 42)
14 (58)
12 (60)
1 (100)
1 (33)
intracranial (n, %)
2 (8)
2 (10)
0
0
genitourinary (n, %)
1 (4)
1 (5)
0
0
no overt (n, %)
3 (13)
2 (10)
0
1 (33)
other (n, %)
4 (17)
3 (15)
0
1 (33)
Site of major bleeding:
gastrointestinal (n, %)
Rubboli A et al. In process
Bhatt DL et al. J Am Coll Cardiol 2008;52:1502-17
Agewall S et al. Eur Heart J 2013;34:1708-15
dabigatran
110 mg BID
dabigatran
150 mg BID
rivaroxaban
20 mg OD
apixaban
5 mg BID
Stroke/Systemic embolism
0.91 *
(0.74-1.11)
0.66 **
(0.53-0.82)
0.88 *
(0.74-1.03)
0.79 **
(0.66-0.95)
Major bleeding
0.80 #
(0.69-0.93)
0.93
(0.81-1.07)
1.04
(0.90-1.20)
0.69 ^
(0.60-0.80)
Intracranial bleeding
0.31 ^
(0.20-0.47)
0.40 ^
(0.27-0.60)
0.67 &
(0.47-0.93)
0.42 ^
(0.30-0.58)
* p<0.05 non-inferiority
** p<0.05 superiority
Connolly SJ et al. N Engl J Med 2009;361:1139-51
# p=0.03
^ p<0.001
&
p=0.02
Granger CB et al. N Engl J Med 2011;365:981-92
Patel MR et al. N Engl J Med 2011;365:883-91
Concomitant Use of Antiplatelet Therapy with Dabigatran or
Warfarin in the Randomized Evaluation of Long-Term
Anticoagulation Therapy (RE-LY®) Trial
Concomitant antiplatelets
Pts.
Pts. on DAPT, %
RR of major bleeding vs. no concomitant APT, HR (95% CI)
6952 (38% of total)
4.5
SAPT 1.60 (1.42-1.82)
DAPT 2.31 (1.79-2.98)
AR/year of major bleeding with DAPT, %
D110/D150/warfarin: 5.4/5.5/6.3
Dans AL et al. Circulation 2013;127:634-40
Medium-term management:
• NOAC to be combined to one or two antiplatelet agents
• lower dose of NOAC* to be considered
• combination therapy to be continued for as short as possible
• newer antiplatelet agents prasugrel and ticagrelor to be avoided
* dabigatran 110 mg BID, rivaroxaban 15 mg OD, apixaban 2.5 mg BID
Heidbüchel H et al. Europace 2013;15:625-51
Triple therapy of VKA + aspirin + clopidogrel/prasugrel after PCI
HR 4.6 (95% CI 1.9-11.4; p<0.001)
HR 1.4 (95% CI 0.3-6.1; p= 0.61)
Sarafoff N et al. J Am Coll Cardiol 2013;61:2060-6
In AF pts. receiving triple therapy after coronary stenting:
1. measures aiming at reducing the risk of bleeding should be carefully implemented #
(%)
2. combination with new antiplatelets prasugrel and ticagrelor to be avoided
3. recommendations valid for warfarin to be generally followed also for NOAC
# short duration (and DES avoidance/limitation + selection), low intensity, gastric protection