Ontstolling in de dagelijkse praktijk casustiek Alles wat u wilt - - PowerPoint PPT Presentation

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Ontstolling in de dagelijkse praktijk casustiek Alles wat u wilt - - PowerPoint PPT Presentation

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Ontstolling in de dagelijkse praktijk casustiek Alles wat u wilt weten over ontstolling en plaatjesremming bij CAD, hartfalen, AF en stents (VKA, NOAC, aspirine, clopidogrel, prasugrel en ticagrelor) Jur ten Berg, cardioloog 1 2016

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SLIDE 1

1

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 praktijk casuïstiek

Jur ten Berg, cardioloog

2016

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SLIDE 2

Disclosures

  • Advisory / consulting fees: AstraZeneca, Eli Lilly,

Daiichi Sankyo, the Medicines Company, Accumetrics, Boehringer-Ingelheim, BMS

  • Research grants: ZonMw, AstraZeneca
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SLIDE 3
  • 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

3

Casus I

  • ASA?
  • 1. Ja
  • 2. nee
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SLIDE 4
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SLIDE 5

Eerste 6 studies meta-analyse ATT Antithrombotic Trialist Collaboration 2009

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SLIDE 6
  • 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

6

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SLIDE 7

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
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SLIDE 8
  • Patiënt 50 jr
  • Hypertensie, ACE-remmer
  • Gedilateerde cardiomyopathie, geen CAD
  • Echo: EF 30%, atria gedilateerd

Casus II HF en SR

8

Vraag:

  • 1. OAC
  • 2. ASA
  • 3. Nix
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SLIDE 9

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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SLIDE 10

1212

Very low EF

Wel indicatie!

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SLIDE 11
  • 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

11

  • 1. OAC
  • 2. ASA
  • 3. OAC en ASA
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SLIDE 12

NOAC = VKA. When combined NOAC plus APT use lower dose NOAC

1212

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SLIDE 13

Casus IV

13

  • 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

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SLIDE 14

BMS versus 1st and 2nd generation DES Results from a registry of 18,334 unselected patients*

14

Jaren na procedure % 3 2 Jaren na procedure % 3 1

Tada T, et al. JACC Cardiovasc Interv 2013

Stent thrombosis Stent thrombosis; 1st year and for the period after the 1st year (separately)

1 1 3 2 1 3 2 2

HR adj. 2,05 0,82 n 18.334 BMS

  • -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

  • -DES

n-DES 95% CI 2,01 – 11,1 0,32 – 3,25 P value <0,001 0,98

* patients undergoing coronary stenting

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SLIDE 15

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

  • r 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

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SLIDE 16

I A

DAPT duration in Stable Coronary Artery Disease

According to ESC Guidelines (not our patient!)

16

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 risk

IIb 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
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SLIDE 17

DAPT N=9000

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12 month observational period: Open-label Thienopyridine + Aspririn required

Placebo + Aspirin Thienopyridines + Aspirin

3 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

12 30 33

Mauri et al. NEJM DOI:10.1056/NEJMoa1409312

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SLIDE 18

DAPT

Primary endpoint

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Maanden na randomisatie

5,6 6,5

12 15 18 21 30 33 % 8 6 4

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

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SLIDE 19

DAPT

Primary endpoint

20

Maanden na randomisatie

0,7 1,4

12 15 18 21 30 33 % 8 6 4

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

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SLIDE 20

DAPT

Primary endpoint

21

Maanden na randomisatie 12 15 18 21 30 33 % 10 8 6

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 2,9 55% of the MI benefit is NOT related to stent thrombosis

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SLIDE 21

DAPT

Bleedings

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TIMI Moderate or Severe % 4 3 2

2,5 1,6 1,7 1,0 0,8 0,6 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

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SLIDE 22

DAPT

Cause for difference in mortality?

23

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%)

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SLIDE 23

An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School

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SLIDE 24

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.

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SLIDE 25

An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School

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SLIDE 26

Reduction in CV death, MI or stroke with ticagrelor by time from P2Y12 inhibitor withdrawal

27

Bonaca 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 Pooled Placebo better Ticagrelor 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

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SLIDE 27

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

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SLIDE 28

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 risk

IIb A

Life-long single antiplatelet therapy, usually ASA, is recommended

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SLIDE 29

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

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SLIDE 30

Study Design: Multicenter, randomized,

  • pen-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

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SLIDE 31

Time to first major bleeding event or clinically relevant non-major bleeding event

Probability of event (%)

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

90 180 270 360 450 540 630 720 Time to first event (days) 40 35 30 25 20 15 10 5

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

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SLIDE 32

Time to death or thromboembolic event, or unplanned revascularization

35 30 25 20 15 10 5 Probability of event (%) 90 180 270 360 450 540 630 720 Time to first event (days) Dabigatran (combined doses) dual therapy Warfarin triple therapy

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SLIDE 33
  • Dual therapy:

– Discharge on NOAC, clopidogrel (12 months), pantoprazole, β-blocker, statin, ACE inhibitor

Case VI