28 november 2019 long term intensive antithrombotic ... · key inclusion & exclusion criteria...
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Long term intensive antithrombotic treatment:
double antiplatelet therapy
Ron Peters
28 november 2019
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Disclosure belangen spreker – Prof.Dr.R.J.G.Peters
WCN 28 november 2019 Double Antiplatelet Therapy
(potentiële) Belangenverstrengeling Geen.
Voor bijeenkomst mogelijk relevante relaties met bedrijven
Sponsors-
• Sponsoring of onderzoeksgeld
• Honorarium of andere (financiële) vergoeding
• (Geen andere relaties)
Research grants:
•Philips
•Weight Watchers
Consultancy fees:
-
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Bonaca M et al. N Eng J Med 2015;372:1791-800
PEGASUS Primary Endpoint
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Key Inclusion & Exclusion Criteria PEGASUS TIMI 54
KEY INCLUSION
• Age ≥50 years
• PLUS at least 1 of the following:
• Age ≥65 years
• Diabetes requiring medication
• 2nd prior MI (>1 year ago)
• Multivessel CAD
• CrCl <60 mL/min
• Tolerating ASA and able to be
dosed at 75-150 mg/d
KEY EXCLUSION
• Planned use of P2Y12 antagonist,
dipyridamole, cilostazol, or anticoagulants
• Bleeding disorder
• History of ischemic stroke, ICH, CNS tumor
or vascular abnormality
• Recent GI bleed or major surgery
• At risk for bradycardia
• Dialysis
• Severe liver disease
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Bonaca M et al. N Eng J Med 2015;372:1791-800
Primary Endpoint
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PEGASUS TIMI 54 NEJM 2015
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Primary Efficacy Outcome (MI/Stroke/CV
Death) by Category of Inclusion
*All patients received ASA 75-162 mg/day
Placebo + ASA*
5.5%
Multiple Risk Factor (N=3,284)
Clopidogrel + ASA*
6.6%
RRR: -20% [95% CI: -58.8%, 9.3%]
p=0.20
Pri
mary
ou
tco
me e
ven
t ra
te (
%)
0
2
4
6
8
10
Months since randomization
0 6 12 18 24 30
Qualifying CAD, CVD or PAD (N=12,153)
Clopidogrel +ASA*
6.9%
Placebo + ASA*
7.9%
RRR: 12.5% [95% CI: 0.2%, 23.2%]
p=0.046
Pri
ma
ry o
utc
om
e e
ve
nt
rate
(%
)
0
2
4
6
8
10
Months since randomization
0 6 12 18 24 30
Bhatt DL. Presented at ACC 2006.
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• Stoppen met roken OR 0,57
• Goede voeding OR 0,52
• Lichaamsbeweging OR 0,52
Chow CK, Jolly S, Rao-Melacini P, Fox KA, Anand SS, Yusuf S. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes. Circulation 2010;121:750–758.
Effect van leefgewoonten:
Kans op recidief binnen 6 maanden
na opname voor acuut coronair syndroom:
OASIS 5 studie (n=18.809)
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• Nederlandse deelnemers (n=700)• meting 1,5 jaar na ontslag wegens ACS• 82% van patienten nog bij cardioloog
• 77% overgewicht BMI >25• 29% obesitas BMI > 30• 78% abdominaal overgewicht (94 en 80 cm)• 43% diabetes volgens WHO• 20% bekend met diabetes• 16% rookt• 50% RR > 140 mmHg• 40% LDL > 2,5 mmol/L (richtlijn CVRM 2011)• 79% LDL > 1,8 mmol/l (richtlijn ESC 2012)
Secundaire preventie in EUROASPIRE 3
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Kaasebrood L., et al Circulation. 2016;134:1419–1429
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SMART cohort, 2nd prevention
• In patients with various manifestations of vascular
disease, median 10-year risk of a recurrent major
vascular event was 17% (interquartile range, 11%–28%),
varying from <10% in 18% to >30% in 22% of the
patients.
• If risk factors were at guideline-recommended targets,
the residual 10-year risk would be <10% in 47% and
>30% in 9% of the patients (median, 11%; interquartile
range, 7%–17%).
Kaasebrood l., et al Circulation. 2016;134:1419–1429
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10 Farmacologische opties voor lange termijn
secundaire preventie, plus aspirine
1. Doorgaan met DAPT (tica, clopi) ?
2. Toevoegen rivaroxaban ?
3. Toevoegen canakinumab CRP?
4. Toevoegen colchicine CRP?
5. Toevoegen evolocumab/alirocumab LDL
6. Toevoegen anacetrapib LDL?
7. Toevoegen inclisiran LDL
8. Toevoegen isosapent ethyl trigl, RR?
9. Toevoegen SGLT2 remmer NTproBNP?
10.Toevoegen GLP1 agonist glucose?
• Op geleide van risicoschatting (‘residual risk’):– Kwantitatief
– Kwalitatief
marker
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Original Article
Low-Dose Methotrexate for the Prevention of Atherosclerotic Events
Paul M Ridker, M.D., Brendan M. Everett, M.D., Aruna Pradhan, M.D., Jean G. MacFadyen, B.A., Daniel H. Solomon, M.D., Elaine Zaharris, B.A., Virak Mam, B.S.,
Ahmed Hasan, M.D., Yves Rosenberg, M.D., Erin Iturriaga, M.S.N., Milan Gupta, M.D., Michelle Tsigoulis, Subodh Verma, M.D., Michael Clearfield, D.O., Peter
Libby, M.D., Samuel Z. Goldhaber, M.D., Roger Seagle, M.D., Cyril Ofori, M.D., Mohammad Saklayen, M.D., Samuel Butman, M.D., Narendra Singh, M.D., Michel
Le May, M.D., Olivier Bertrand, M.D., James Johnston, M.D., Nina P. Paynter, Ph.D., Robert J. Glynn, Sc.D., for the CIRT Investigators
N Engl J MedVolume 380(8):752-762
February 21, 2019
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vraagtekens
• Bescheiden behandeleffecten (hoge NNT)
• Gemiddelde risico’s in populaties
• Gemiddelde behandeleffecten in populaties
• Geselecteerde populaties
• RCT vs cohorten
• Veel individuele determinanten van risico niet bekend
• Nadelen van polyfarmacie
• Beperkingen aan therapietrouw
• Beperkingen aan betaalbaarheid
16
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NACCE at 1-Year Follow-up(All-cause death, any MI, stroke, or major bleeding)
• Follow-up rate:
99.3% for CP and TP
CHANGE DAPT
Von Birgelen et al EuroIntervention. 2017 Nov 20;13(10):1168-1176
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JAMA 2016;315: 1735-49
Risicoschatting kwantitatief
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Nieuwe opties voor lange termijn secundaire preventie
voorkomen van sterfte, infarct, beroerte
• Doorgaan DAPT (tica) DAPT score <2 153 3
• Doorgaan DAPT (tica) DAPT score ≥2 34 3
• Doorgaan DAPT (clopidogrel) 200 2,5
• Toevoegen rivaroxaban 77 2
• Toevoegen canakinumab 33 3,5
• Toevoegen colchicine 62 2
• Toevoegen evolocumab/alirocumab 63 4
• Toevoegen anacetrapib 100 4
• Toevoegen Isosapent ethyl 20 5
• Toevoegen inclisiran ? ?
NNT, jaren
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U weet meer dan de calculator
• Leeftijd
• Vitaliteit
• Therapietrouw
• Streefwaarden gehaald (LDL, bloeddruk)?
• Lp(a)
• T2DM: DAPT score, GLP1 agonist indicatie?
• CHF: GLP2i indicatie?
• Coronaire anatomie, stents, grafts, advies interventiecollega
• Bloedingsneiging
• Voorkeur van de patient
• Familie anamnese
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82 jaar
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82 jaar
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Vein graft failure Stented left main bifurcation
‘DAPT’ for life? ‘DPI’ for life?
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Figure 1. Photomicrographic cross section of human coronary plaque rupture (PR), thin-capped fibroatheromas (TCFA),
and fibroatheromas (FA) with varying degree of luminal stenosis
(A–C). PR with mild, moderate, and severe luminal stenosis, respectively. Nonocclusive thrombus (Thr) is observed in the
microphotograph A, whereas occlusive Thr is occupying the lumen in B and C.
D, E, and F, TCFA with mild, moderate, and severe luminal stenosis, respectively. Necrotic core (NC) is covered by a thin fibrous
cap, and Thr is not present in the lumen.
G, H, and I, Stable plaque or FA with mild, moderate, and severe luminal stenosis, respectively. The size of necrotic core is
relatively small when present, and calcification (Ca++) is frequently seen.
Narula J, et al. J Am Coll Cardiol. 2013; 61:1041–1051.
Thrombotic risk varies widely among CAD patients.
Thin cap
Stable plaque
Thrombus
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Individualisering, kwalitatief
• Doorgaan DAPT rokers?
• Toevoegen rivaroxaban (jonge leeftijd?)
• Toevoegen canakinumab CRP ↑
• Toevoegen colchicine CRP ↑
• Toevoegen evolocumab/alirocumab LDL ↑
• Toevoegen anacetrapib HDL ↓
• Toevoegen Isosapent ethyl trigl↑, Hypertensie
• Toevoegen inclisiran LDL ↑
categorie
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Smoking stimulates platelet activation and aggregation
Ex vivo platelet thrombus formation on porcine arterial media
Hung et al. Circulation. 1995;92:2432–2436
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COMPASS: rivaroxaban 2,5 mg or placebo o.t.o. aspirin
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The Doctor, Sir Luke Fildes, 1891
Tate Gallery
‘Personalised Medicine’
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Conclusies
• Grote individuele verschillen in ‘residual risk’
• Slechts een deel daarvan is meetbaar
• U weet meer dan de calculator
• Grote NNT bij gemiddelde studiepopulaties
• RCT ≠ iedereen
• Bij veel patiënten is de standaard medicatie voldoende
• Maatwerk is nodig, bespreken met patiënt
• Is de angel eruit?
• Betrek de leefgewoonten in de evaluatie
• Doe meer aan de leefgewoonten
• NB: Na enkele jaren heroverwegen
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Kortste versie, 2019:
• Doe eerst de gewone dingen heel goed, inclusief
leefgewoonten
• Bij geselecteerde patiënten is er een reden om meer te
doen. Documenteer, evalueer periodiek.
• Huidige opties:
– tica 2 x 60 mg of clopi 1 x 75 mg toevoegen: DAPT
– rivaroxaban 2 x 2,5 mg toevoegen: DPI
– PCSK9 remmer toevoegen