Ontstolling in de dagelijkse praktijk casuïstiek · • AF en CVA 1990 • Ischemische...
Transcript of Ontstolling in de dagelijkse praktijk casuïstiek · • AF en CVA 1990 • Ischemische...
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Alles wat u wilt weten over ontstolling en plaatjesremming bij CAD, hartfalen, AF en stents (VKA,
NOAC, aspirine, clopidogrel, prasugrel en ticagrelor)
Ontstolling in de dagelijkse praktijkcasuïstiek
Jur ten Berg, cardioloog
2016
Disclosures
• Advisory / consulting fees: AstraZeneca, Eli Lilly,
Daiichi Sankyo, the Medicines Company,
Accumetrics, Boehringer-Ingelheim, BMS
• Research grants: ZonMw, AstraZeneca
• Patiënt 65 jaar• Asymptomatisch. “Krijg ik ook een hartinfarct, fam
belast voor HVZ”• Hypertensie sinds 50e, ACE-remmer• Rookt, hypercholesterolemie (TCh 6; LDL 3,5 mmol/l)• Vader 55 AMI en 70 colon ca
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Casus I
• ASA?
1. Ja2. nee
Eerste 6 studies meta-analyse ATT Antithrombotic Trialist Collaboration 2009
• Per 10.000 treated for 10 years
• 72 events (CV death, MI, or stroke) prevented• 51 cancer deaths prevented• 47 major bleedings (149 GI bleeds) incurred• 9 hemorrhagic strokes incurred
• Effect man=woman• DM not sufficient risk
• Bleeding as severe as MI?
Casus I
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Tailoring therapy according to baseline risk
• Framingham coronary heart disease risk score: 10-jr MI/death
• ESC’s SCORE: 10-jr fatal atherosclerotic event 5% fatal ~ 15% (x3) total
events
• Patient 17% risk (ESC’s SCORE): antwoord 1: ja aspirine
• Patiënt 50 jr
• Hypertensie, ACE-remmer
• Gedilateerde cardiomyopathie, geen CAD
• Echo: EF 30%, atria gedilateerd
Casus II HF en SR
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Vraag: 1. OAC
2. ASA
3. Nix
Hartfalen en SR
No placebo
• Death, non-fatal MI, non-fatal stroke: Warfarin = aspirin
• Major bleeding: warfarin higher
• Stroke: warfarin lower
• Wash studie: no medication similar to ASA or warfarin
ASA vs warfarin
ASA vs warfarin vs No
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Very low EF
Wel indicatie!
• Patiënt 60 jr
• Hypertensie, ACE-remmer
• AF en CVA 1990
• Ischemische cardiomyopathie
• Stabiel AP II CCS, PCI DES 2013
• Echo: EF 30%, murale trombus, atria gedilateerd
• ECG: SR, lichte ST-T afw
Casus III Hf en coronairlijden
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1. OAC2. ASA3. OAC en ASA
NOAC = VKA. When combined NOAC plus APT use lower dose NOAC
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Casus IV
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• Man 55 jaar, DM II, in 2012 OWI, hypertensie met GFR = 48 ml/min, rookt.
• STEMI 4 oktober 2016 DES proximale LAD, 9 oktober PCI Cx en diffuus RCA
• Geen recidief, geen bloeding
• 4 oktober 2017 polikliniek
a) P2Y12 remmer (ticagrelor) had al gestopt moeten zijn
b) Nu stop
c) Nog jaren continueren
BMS versus 1st and 2nd generation DES
Results from a registry of 18,334 unselected patients*
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Jaren na procedure
% 3
0
2
Jaren na procedure
% 3
0
1
Tada T, et al. JACC Cardiovasc Interv 2013
Stent thrombosis Stent thrombosis; 1st year and for the period
after the 1st year (separately)
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0 1 32 0 1 32
2
HR adj.
2,05
0,82
n
18.334
BMS
o-DES
n-DES
95% CI
1,47 – 2,86
0,56 – 1,19
P value
<0,001
0,30
HR adj.
4,72
1,01
n
18.334
BMS
o-DES
n-DES
95% CI
2,01 – 11,1
0,32 – 3,25
P value
<0,001
0,98
* patients undergoing coronary stenting
Meta-analysis
Trial EXCELLENT PRODIGY REAL/ZEST-LATE
RESET
Primary endpoint Composite of cardiac death, MI, or ID-TVR
Composite of all-cause death, MI or CVAs
MI or cardiac death Composite of cardiac death, MI, ST, ID-TVR and TIMI major
or minor bleeding
Time to randomization At index PCI 1 month after index PCI 12 months after index PCI
At index PCI
DAPT duration
Extended DAPT Group
12 months 24 months 24 months 12 months
Control DAPT Group 6 months 6 months 12 months 3 months
Longest FU 12 months 24 months 24 months 12 months
Kort DAPT even veilig als lang DAPT
12,536 pts randomized to stop DAPT at 3, 6 or 12 months vs. 12 or 24 months
Collet J et al. Lancet. 2014 Jul 15. pii: S0140-6736(14)60612-7. doi: 10.1016/S0140-6736(14)60612-7
I A
DAPT duration in Stable Coronary Artery Disease
According to ESC Guidelines (not our patient!)
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DAPT is indicated for at least 1 month after BMS implantation
Recommendations for antithrombotic treatment in patients with SCAD undergoing PCI
I A
DAPT is indicated for 6 months after DES implantation I B
Myocardial revascularization Guidelines (2014)
Shorter DAPT duration (<6 months) may be considered after DES implantation in patients at high
bleeding riskIIb A
Life-long single antiplatelet therapy, usually ASA, is recommended
Instruction of patients about the importance of complying with antiplatelet therapy is recommended I C
DAPT may be used for more than 6 months in patients at high ischemic risk and low bleeding risk IIb C
Windecker et al. Eur Heart J 2014;35(37):2541-619
Pas op:
• Studies merendeel low risk patienten
• Geen power om een verschil in stent trombose aan te tonen
DAPT N=9000
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12 month observational
period: Open-label
Thienopyridine + Aspririn
requiredPlacebo + Aspirin
Thienopyridines + Aspirin3 month observational
period:
Off Thienopyridine +
On Aspririn
Time in months after index stent
procedure (not scale)
Previous studies underpowered
Designed in response to FDA-request
R Study drug
treatment ends
Free from MI, stroke, repeat revascularization and bleeding, adherent to P2Y12
0 12 30 33
Mauri et al. NEJM DOI:10.1056/NEJMoa1409312
DAPT
Primary endpoint
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Maanden na randomisatie
5,6
6,5
0 12 15 18 21 30 33
% 8
6
4
0
Mauri et al. NEJM DOI:10.1056/NEJMoa1409312
Death, MI, Stroke
24 27
2
HR
0,29
P value
<0,001
n
9.961
12 months
30 months
4,3
5,9
95% CI
0,59 – 0,85
DAPT
Primary endpoint
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Maanden na randomisatie
0,7
1,4
0 12 15 18 21 30 33
% 8
6
4
0
Stent Thrombosis
24 27
2
0,4
1,4
HR
1,03
95% CI
0,17 – 0,48
P value
0,03
n
9.961
12 months
30 months
Mauri et al. NEJM DOI:10.1056/NEJMoa1409312
DAPT
Primary endpoint
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Maanden na randomisatie
0 12 15 18 21 30 33
% 10
8
6
0
Not-Stent Thrombosis Myocardial Infarction
24 27
4
HR
0,59
95% CI
0,45 – 0,78
P value
<0,001
n
9.961
12 months
30 months
Mauri et al. NEJM DOI:10.1056/NEJMoa1409312
1,8
2,955% of the MI
benefit is NOT
related to stent
thrombosis
DAPT
Bleedings
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TIMI
Moderate or
Severe
% 4
3
2
0
2,5
1,61,7
1,0
0,80,6
3,1
1,5
2,6
1,5
0,1 0,1
0,001
0,004
0,15
<0,001
<0,001
0,38
Moderate Severe BARC
Type 2
BARC
Type 3
BARC
Type 5
12 months
30 months
1
DAPT
Cause for difference in mortality?
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12-30 M mortality
All cause mortality
Cardiac
Vascular
Non-cardiovascular
(bleeding, trauma, cancer)
Mauri et al. NEJM DOI:10.1056/NEJMoa1409312
Thienopyridine
N=5.020
98 (2,0%)
45 (0,9%)
5 (0,1%)
48 (1,0%)
Placebo
N=4.941
74 (1,5%)
47 (1,0%)
5 (0,1%)
22 (0,5%)
P value
0,052
0,98
0,98
0,002
Absolute
Difference
24 (0,5%)
-2 (-0,1%)
0 (-)
26 (0,5%)
An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
N= 21.000
age of 65 years or older, diabetes mellitus requiring medication, a second prior spontaneous myocardial infarction, multivessel coronary artery
disease, or chronic renal dysfunction, defined as an estimated creatinine clearance of less than 60 ml per minute.
An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Reduction in CV death, MI or stroke with ticagrelor by time from P2Y12 inhibitor withdrawal
27Bonaca MP et al. Eur Heart J 2016; 37(14): 1133-42
0.70 (0.57, 0.87)
0.75 (0.61, 0.92)
0.73 (0.61, 0.87) <0.001
0.90 (0.72, 1.12)
0.82 (0.65, 1.02)
0.86 (0.71, 1.04) 0.11
0.96 (0.73, 1.26)
1.06 (0.81, 1.38)
1.01 (0.80, 1.27) 0.96
Ticagrelor 90 mg
Ticagrelor 60 mg
PooledPlacebo betterTicagrelor better 1.0
HR (95% CI) P value
≤30 days
n=7181
>30 days
to 1 year
n=6501
>1 year
n=5079
Time from P2Y12 inhibitor withdrawal to
randomization
P-interaction 0.0097
27% RRR
14% RRR
RRR
0.7 0.9 1.1
Casus IV
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• Man 40 jaar, DM I, hypertensie met GFR = 48 ml/min, rookt, fam HVZ
• STEMI 4 oktober 2016 DES proximale LAD, 9 oktober PCI Cx en diffuus RCA
• Geen recidief, geen bloeding
• 4 oktober 2017 polikliniek
a) P2Y12 remmer (ticagrelor) had al gestopt moeten zijn
b) Nu stop
c) Nog jaren continueren
PEGASUS: age of 65 years or older, diabetes mellitus requiring medication, a
second prior spontaneous myocardial infarction, multivessel coronary artery
disease, or chronic renal dysfunction, defined as an estimated creatinine
clearance of less than 60 ml per minute.
DAPT: no event first year
Casus V
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• Vrouw 87 jaar, 57 kg, hypertensie, maag bloeding ulcus 2013
• NSTEMI en PCI DES prox LAD succesvol 21 sept 2016
a) 1 jaar DAPT
b) 6 maanden DAPT
c) 3 maanden DAPT
I A
DAPT is indicated for at least 1 month after BMS implantation I A
DAPT is indicated for 6 months after DES implantation I B
Shorter DAPT duration (<6 months) may be considered after DES implantation in patients at high
bleeding riskIIb A
Life-long single antiplatelet therapy, usually ASA, is recommended
I C
Personal Information
Sex Male
Age 83
Blood pressure 161/89 mmHg
Pulse 69 bpm
Oxygen saturation 97%
Patient: Paul*
Patient History
Medical History
• Hypertension (diagnosed 2004)
• Type 2 diabetes mellitus
• Paroxysmal NVAF (diagnosed 2012;
CHA2DS2-VASc: 5)
• Peripheral artery disease
• Renal insufficiency (GFR = 38 ml/min)
Medications
• β-blocker
• Statin
• ACE inhibitor
• Antidiabetics
• NOAC since 2013 (because of labile INR/low TTR)
Presentation • Heavy chest pain (40 min, previous night)
• Pain-free at presentation
• Nonstemi
Case VI
Study Design: Multicenter, randomized, open-label trial following a PROBE design
R
Randomization
≤120 hours
post-PCI* 6-month minimum treatment duration with visits every 3 months for the first year, then visits
and telephone contact alternating every 3 months and a 1-month post-treatment visit
Patients with AF
undergoing PCI
with stenting
no recent Stroke
CrCl <30mL/min
Dabigatran 150 mg BID + P2Y12 inhibitor
Dabigatran 110 mg BID + P2Y12 inhibitor
Warfarin (INR 2.0–3.0) + P2Y12 inhibitor + ASA
Dabigatran (110 or 150 mg)
Warfarin
1 month of ASA (BMS)3 months of ASA (DES)
N=2725
Mean duration of
follow-up:
~14 months
P2Y12 inhibitor
P2Y12 inhibitor
Time to first major bleeding event or clinically relevant non-major bleeding event
Pro
ba
bil
ity o
f e
ve
nt
(%)
0
0 90 180 270 360 450 540 630 720
Time to first event (days)
40
35
30
25
20
15
10
5
Warfarin
triple therapy
Dabigatran 110 mg
dual therapy
HR: 0.52 (95% CI: 0.42–0.63)
Non-inferiority P<0.0001
P<0.0001
0 90 180 270 360 450 540 630 720
Time to first event (days)
40
35
30
25
20
15
10
5
0
Dabigatran 150 mg
dual therapy
Warfarin
triple therapy
HR: 0.72 (95% CI: 0.58–0.88)
Non-inferiority P<0.0001
P=0.002
Time to death or thromboembolic event, orunplanned revascularization
35
30
25
20
15
10
5
0
Pro
bab
ilit
y o
f ev
en
t (%
)
0 90 180 270 360 450 540 630 720
Time to first event (days)
Dabigatran (combined doses)
dual therapy
Warfarin
triple therapy
• Dual therapy:
– Discharge on NOAC, clopidogrel (12 months), pantoprazole,
β-blocker, statin, ACE inhibitor
Case VI