3.1 Latest News on Antiplatelet - Dr. Rurus Sp.jp

8/18/2019 3.1 Latest News on Antiplatelet - Dr. Rurus Sp.jp

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Latest News on Antiplatelets

Rurus Suryawan,MDDepartment of Cardiology and Vascular Medicine , Dr SoetomoHospi ta l -Facul ty of Medicine , Air langga Univers i ty, Surabaya,

Indonesia .


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Current Hot Issues on Antiplatelets

• EARLY Pre Treatment of DAPT in NSTEMI• DAPT beyond 12 months


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ACCOST Trial


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A C omparison of prasugrel at the time of percutaneousC oronary intervention O r as pretreatment At the timeof diagnosis in patients with non -ST -elevation MI

•

Pre-treatment with aspirin and a P2Y 12 antagonist has been a clasrecommendation and common practice for the treatment of NSTE-ACS

• However, no trial has ever randomized patients presenting with

NSTE-ACS, invasively managed, to pre-treatment with clopidogrelprasugrel or ticagrelor vs. no pre-treatment.


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ACCOAST design

Prasugrel 30 mg

Prasugrel 60 mgPrasugrel 30 mg

Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days

PCI

1° Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa bailout, at 7 days

Placebo

CoronaryAngiography

n~4100 (eve

CoronaryAngiography

PCI

CABGor

Medical

Management(no more prasugrel)

Montalescot G

Randomize 1:1Double-blind

NSTEMI + Troponin ≥ 1.5 times ULN local lab valueClopidogrel naive or on long term clopidogrel 75 mg


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Days From First Dose0 5 10 15 20 25

E n

d p o

i n t

( % )

0

5

10

15

19962037

17881821

17751809

17691802

17621797

17521791

CV Death, MI, Stroke,UR, GPIIb/IIIa Bailout

No. at Risk, PrimaryEfficacy End Point:No pre-treatmentPre-treatment

Pre-treat110.0Pre-treatment

Hazard Ratio, 0

(95% 0.83, 1.20P=0.98P=0.81(95% 0.84, 1.25)

Hazard Ratio, 1.02

No Pre-trea1

9.8No Pre-treatment

1° Efficacy End Point @ 7 + 30 days(All Patients)


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All TIMI (CABG or non-CABG) Major Bl(All Treated patients)

Days From First Dose0 5 10 15 20 25

E n d p o i n t ( % )

0

1

2

3

4

5

All TIMI Major Bleeding

Pre-treatmen2.9

Pre-treatment2.6

No Pre-treatme1.

No Pre-treatment1.4

19962037

19471972

13281339

12971310

12881299

12841297

No. at Risk, All TIMIMajor Bleeding:No pre-treatmentPre-treatment

Hazard Ratio, 1.9(95% 1.26, 3.08)P=0.002

Hazard Ratio, 1.90(95% 1.19, 3.02)P=0.006


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Conclusions• In NSTE-ACS patients managed invasively within 48 hours

admission, pre-treatment with prasugrel does not reduce maischemic events through 30 days but increases major bleedicomplications.

• The results are consistent among patients undergoing PCIsupporting treatment with prasugrel once the coronary anato

has been defined.• Reappraisal of routine pre-treatment strategies in NSTE-AC

needed.


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Latest News

• Hot Issue : DAPT (Dual Anti Platelet Therapy beyond 12 m


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Mauri L., et al, 2015 ESC


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• Following drug-eluting stent treatment, continuation of thienopyridine plusaspirin beyond one year reduces the risk of stent thrombosis and MACCEcompared with aspirin alone.

•Relative reductions of 71% for ST, 29% for MACCE and 53% for MI

•The benefit of extended thienopyridine treatment was tempered by an incin bleeding events (relative increase, 61%). Severe and/or fatal bleeding wasuncommon.

CONCLUSIONS


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PEGASUS-TIMI 54A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED,PARALLE L-GROUP, MU LTINATIONAL TRIAL TO ASSESS THE P REVOF THROMBOTIC EVENTS WITH TICAGRELOR COMPARED WITH ON A BACKGROUND OF ACETYLSALICYLIC ACID THERAPY IN P

WITH A HI STORY OF MYOCARDIAL INFARCTION


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PEGASUS-TIMI 54: Rationale• Patients who have suffered a MI are at heightened risk of recurrent ischaem

• The recent APOLLO-HELICON registry highlighted that 1 in 5 patients who remain evpost-MI will go on to suffer another MI, a stroke, or die from CV causes in the subseque

• These data suggest that patients with a history of MI may derive particular benefit from secondary prevention strategies

• The role of P2Y 12 receptor antagonists in long-term secondary prevention anot been established

•

Both US and European ACS practice guidelines currently recommend treatmP2Y12 receptor antagonist for up to 1 year after MI 4–7

CV, cardiovascular; MI, myocardial infarction

1. Bhatt DL et al . JAMA2010;304:1350–13572. Fox KAet al. Eur Heart J 2010;31:2755–27643. Jernberg T et al . Eur Heart J 2015; pii: ehu505 [Epub ahead of print]4. Amsterdam EA et al. Circulation 2014;130:2354–23945. Hamm CW et al . Eur Heart J 2011;32:2999 –30546. O'Gara PT et al . Circulation 2013;127:e362–4257. Steg PG et al. Eur Heart J 2012;33:2569–2619


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PEGASUS-TIMI 54: Study DesignPatients aged ≥50 years with a history of spontaneous MI 1– 3 years prior to enrolment AND a

additional atherothrombosis risk factor*(N=21,162)

Ticagrelor 60 mg bid+ ASA 75–150 mg/day

Minimum of 12 months’ follow up:

Every 4 months in Year 1,then semi-annually

Primary efficacy endpoint: CV death, MI or strokePrimary safety endpoint: TIMI-defined major bleeding

P+ ASA 7

Ticagrelor 90 mg bid+ ASA 75–150 mg/day

*Age ≥65 years, diabetes mellitus, second prior MI, multivessel CAD or chronic non-end stage renal diseasebid, twice daily; CAD, coronary artery disease; TIMI, Thrombolysis in Myocardial Infarction

Bonaca MP et al.Am Heart J 2014;167:437–444Bonaca MP et al . N Engl J Med 2015 [Epubahead of print]


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PEGASUS-TIMI 54: Follow-up

IQR, interquartile range

Bonaca MP et al . N Engl J Med2015 [Epub ahead of print]

Randomised 21,162 patients

Ticagrelor 60 mgbid

(N=7045)

Follow-up median 33 months (IQR 28 –37)Range 14 –48 months

Placeb(N=706

Ticagrelor 90 mgbid

(N=7050)

Premature permanent drugdiscontinuation n=2233 (32%) n=1999 (29%) n=1496 (21%

Withdrew consent n=52 (0.7%) n=50 (0.7%) n=52 (0.7%

Lost to follow-up n=3 (


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EndpointTicagrelor90 mg bid

N=7050; n (%)

Ticagrelor60 mg bid

N=7045; n (%)

PlaceboN=7067; n (%)

Ticagrelor90 mg bid vs

placeboHR (95% CI)

Primary endpoint

CV death, MI orstroke 493 (7.85) 487 (7.77) 578 (9.04)

0.85 (0.75–0.96)P=0.008

Secondary endpoints

CV death 182 (2.94) 174 (2.86) 210 (3.39)0.87 (0.71–1.06)

P=0.15Death from anycause 326 (5.15) 289 (4.69) 326 (5.16)

1.00 (0.86 –1.16)P=0.99*

Other efficacy endpoints

MI 275 (4.40) 285 (4.53) 338 (5.25)0.81 (0.69 –0.95)

P=0.01*

All stroke 100 (1.61) 91 (1.47) 122 (1.94)0.82 (0.63 –1.07)

P=0.14*

Ischaemic stroke 88 (1.41) 78 (1.28) 103 (1.65)0.85 (0.64 –1.14)

P=0.28*

PEGASUS-TIMI 54: Efficacy Endpoints

*Indicates nominal P value; P


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EndpointTicagrelor90 mg bid

N=6988; n (%)

Ticagrelor60 mg bid

N=6958; n (%)

PlaceboN=6996; n (%)

Ticagrelor90 mg bid vs

placeboHR (95% CI)

Primary safety endpoint

TIMI major bleeding 127 (2.60) 115 (2.30) 54 (1.06) 2.69 (1.96 –3.70)P


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PEGASUS-TIMI 54: Bleeding

0

1

2

3

4

5

TIMI major bleeding TIMI minor bleeding Fatal bleeding or ICH ICH

Ticagrelor 90 mg bid Ticagrelor 60 m

3 - y e a r

K M

e v e n t r a t e

2.62.3

1.1

1.3 1.20.4

0.6 0.70.6 0.6 0.6 0.5

0.1

Rates are presented as 3-year Kaplan-Meier estimatesP


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PEGASUS-TIMI 54:Analyses of Net Clinical Benefit

Ticagrelor 90 mg bid versus placebo Ticagrelor 60 mg bid

Characteristic RRR HR (95%CI) P value RRR HR (95%

Net clinical benefit: CVdeath, MI, stroke, or TIMImajor bleeding

0% 1.00(0.90–1.22)

0.9563 5% 0.95(0.85–1

Irreversible harm:CV death, MI, stroke, ICH andfatal bleeding

12% 0.88

(0.78–0.99)

0.0372 14% 0.86

(0.77–0

Rates are annualised from 3-year Kaplan-Meier event rates in the intention-to-treat populationRRR, relative risk reduction

*Data on file: ATLAS approval ID 691,431.011


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Conclusions• DAPT (ASA+Prasugrel) pre treatment before coronary

angiography available is Contraindicated (base on ACCOST trial)• DAPT (ASA+ Clopidogrel or Ticagrelol) have not been evaluated

for pre treatment before Angiography is available• DAPT in Post PCI with DES beyond 12 months has reduced

Ischemic event and stent thrombosis but associated with modestincreased of bleeding (Thienopyridine/Clopidogrel or Prasugrel)

• The DAPT in high risk 1-3 years post MI: ASA + Ticagrelor beyon12 months reduced ischaemic events but associated with increasebleeding


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2015 ESC NSTEMI Guidelines


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