Heartline 2014
Genova 14 – 15 Novembre 2014
Sindromi coronariche acute
nei pazienti con fibrillazione atriale :
possiamo utilizzare in associazione
NAO ed inibitori P2Y12 ?
Luigi Oltrona Visconti
Divisione di Cardiologia
IRCCS Fondazione Policlinico S. Matteo
Pavia
Condition
ACS
Stented patients
AF
DVT
PE
LV thrombus
(Mechanical) valves
Aim :
Prevention of
Coronary Ischemic events Stroke
Stent thrombosis
Systemic embolism
Evidence
DAPT better than VKA
VKA better than DAPT
Duration
1 – 6 – 12 months
Sometimes lifelong
ESC Guidelines
Condition
Year
Duration
IA
2011
1 year
STEMI
I A (B)
2012
1 year
Elective BMS
Elective DES
I A (B)
I A (B)
2014
1 month
6 months
IA
2012
Lifelong
NSTEMI
AF
Drugs
Recommandation/
Evidence Level
DAPT
VKA
NOACS
LOV 2014
However ….
Up to 30% of AF patients on
VKA have CAD and are
potential candidates to DAPT
Between 5% to 10% of pts
undergoing stent implantation
necessitate anticoagulant
treatment
LOV 2014
Heartline 2014
Genova 14 – 15 Novembre 2014
What to do ?
LOV 2014
VKA + antiplatelets
Reduces the risk of thrombotic events
but
increases bleeding risk up to 3-5 fold
Haemorragic risk
Thrombotic risk
Heartline 2014
Genova 14 – 15 Novembre 2014
VKA + antiplatelets
No definitive data
are available
LOV 2014
ISAR-TRIPLE
(http://clinicaltrials.gov/show/NCT00776633)
• 600 pts
• Indication to VKA+DES (ACS or elective)
• 9-month follow-up
• Composite endpoint : death, MI, stroke, ST, TIMI-bleeding
MUSICA-2
(http://clinicaltrials.gov/ct2/show/NCT01141153)
•
•
•
•
304 pts
Indication to VKA + BMS or DES (ACS or elective)
CHADS2 score <2
12-month follow-up
• Composite endpoint : stroke, SE, death, MI, ST, TVR, TIMIbleeding
Triple vs DAPT (ASA + clopidogrel)
Condition
ACS
Stented patients
Aim :
Ischemic events
Prevention of Stent thrombosis
AF
DVT
PE
LV thrombus
(Mechanical) valves
Stroke
Systemic embolism
Evidence
DAPT better than VKA VKA better than DAPT
Duration
1 – 6 – 12 months
Sometimes lifelong
Complication of the picture (1) :
New P2Y12 inhibitors
in association with VKA ?
LOV 2014
In both
PLATO (ticagrelor)
and
TRITON-TIMI 38 (prasugrel)
studies
patients were excluded from enrollment
if receiving VKA
LOV 2014
Condition
ACS
Stented patients
Aim :
Ischemic events
Prevention of Stent thrombosis
AF
DVT
PE
LV thrombus
(Mechanical) valves
Stroke
Systemic embolism
Evidence
DAPT better than VKA VKA better than DAPT
Duration
1 – 6 – 12 months
Sometimes lifelong
Complication of the picture (2) :
NOACS
in association with DAPT
(aspirin+clopidogrel) ?
LOV 2014
In all
NOACS trials
( RELY, ROCKET-AF, ARISTOTLE)
patients were excluded from enrollment
if receiving new P2Y12
LOV 2014
NOACS
in association with DAPT
(aspirin+clopidogrel) ?
Some data are available
in non AF patients
LOV 2014
Primary Outcome
CV Death, MI, Ischemic Stroke
Apixaban
279 (7.5%)
Placebo
293 (7.9%)
HR 0.95; 95% CI 0.80-1.11; p=0.509
TIMI Major Bleeding
Apixaban
48 (1.3%)
Placebo
18 (0.5%)
HR 2.59; 95% CI 1.50–4.46; p=0.001
ATLAS ACS 2 TIMI 51
N=15,526*
Physician's decision to add thienopyridine or not
Stratum 1: ASA
alone (7%)
Placebo
n=355
Rivaroxaban
2.5 mg bid
n=349
ASA dose =
75–100 mg/day
Rivaroxaban
5 mg bid
n=349
Stratum 2: ASA +
thienopyridine (93%)
Placebo
n=4821
Rivaroxaban
2.5 mg bid
n=4825
Rivaroxaban
5 mg bid
n=4827
Event-driven study – 1002 events
*184 patients were excluded from the efficacy analyses prior to unblinding because of trial misconduct
at three sites
Mega et al, 2011
Primary efficacy endpoint (CV death/MI/stroke)
Both rivaroxaban doses, both strata
Estimated cumulative rate (%)
12
2-year Kaplan–Meier estimate
10.7%
10
Placebo
8.9%
8
Rivaroxaban
6
HR=0.84
(0.74–0.96)
ARR=1.7%
mITT p=0.008
4
ITT p=0.002
NNT=56
2
0
0
Number at risk
Placebo
5113
Rivaroxaban 10,229
Mega et al, 2011
4
4307
8502
16
8
12
Months after randomization
3470
6753
2664
5137
1831
3554
20
24
1079
2084
421
831
Principal safety endpoint
Separate rivaroxaban doses, both strata
Non-CABG TIMI major bleed
K–M estimate at 2 years
p value versus placebo
ICH
K–M estimate at 2 years
p value versus placebo
Fatal bleeding
K–M estimate at 2 years
p value versus placebo
Fatal ICH
K–M estimate at 2 years
p value versus placebo
Mega et al, 2011
Rivaroxaban
2.5 mg bid
(n=5115)
Rivaroxaban
5 mg bid
(n=5110)
1.8%
<0.001
2.4%
<0.001
0.6%
0.4%
0.04
0.7%
0.005
0.2%
0.1%
0.45
0.4%
0.20
0.2%
0.1%
–
0.2%
–
0.1%
Placebo
(n=5125)
What is the future ?
(in patients requiring DAPT
+ OAC for AF stroke prevention )
LOV 2014
PIONEER AF PCI
2200 patients
The RE-DUAL PCI™ trial
(Randomized Evaluation of Dual Therapy with Dabigatran vs. Triple Therapy
Strategy with Warfarin in Patients with NVAF that have undergone PCI with
Stenting)
Patients undergoing PCI
Dabigatran (150 mg or 110 mg twice daily) + single antiplatelet
therapy with a P2Y12 protein inhibitor
compared to
warfarin + two antiplatelet agents
to assess
clinically relevant bleeding and thrombotic events (combined rate
of death, myocardial infarction and stroke)
2014 messages for the daily clinical practice
in AF patients requiring DAPT + OAC (1)
Indication :
• DAPT (clopidogrel + ASA)
• Single APT(clopidogrel or ASA)
+ VKA (= triple)
+ VKA (= WOEST)
No indication :
• DAPT (ASA + prasugrel or ticagrelor) + VKA
• DAPT (ASA + clopidogrel)
+ NOACs
• DAPT (ASA + prasugrel or ticagrelor) + NOACs
2014 messages for the daily clinical practice
in AF patients requiring DAPT + OAC (2)
• ? Combination of drugs
• ? Duration of therapy
• Reduce intensity of VKA (INR 2.0 - 2.5)
• Prefer BMS
• Prefer radial access
• Evaluate clinical circumstances (ACS, elective stent)
• Evaluate bleeding risk profile (PPI, BP control, NSAID)
Patients with atrial fibrillation + Stent (ACS or Elective)
1 month
6 months
12 months
BMS VKA*---------------------------------------------------- --
ASA ----------------
Clopidogrel--------
DES
VKA*---------------------------------------------------- --
ASA --------------?------------------?------------------
Clopidogrel ------------------------?------------------
* = INR 2.0-2.5
In low thrombotic risk DAPT is an alternative