Antiplatelet Update in ACS :

Whats New ?
Rurus Suryawan
Dept.of Cardiology and Vascular
Medicine, Dr.Soetomo General
Hospital, Faculty of Medicine, UNAIR
 Acute thrombosis induced by a
ruptured or eroded
atherosclerotic coronary plaque,
with or without concomitant
vasoconstriction, causing a
sudden and critical reduction in
blood flow

Hamm CW et al. Eur Heart J 2011;32:2999 3054

2
 Antithrombotic in ACS

Hamm CW et al. Eur Heart J 2011;32:2999 3054 3

 Objectives of DAPT
Prevent and reduce ischemic events during and
after PCI
* Prevent Stent Thrombosis
* Prevent MI
* CV death
* Re Intervention
Without excessive bleeding complications
 Balancing Risk and Benefit

History Prior
Bleeding
Advanced age OAC therapy
ACS presentation Female
Multiple prior MI Advanced age
Extensive CAD CKD
Diabetes Diabetes
CKD Anemia
Chronic NSAID
therapy
 STENT THROMBOSIS

ARC classification:
4 years Cumulative Incidence (1st generation stent):
Sirolimus ES vs BMS 1.5 % vs 1.7 %
Paclitaxel ES vs BMS 1.8 % vs 1.4%

Mauri L. et al. N Engl J Med 2007;356:1020-9.

 Antiplatelet recommendation in Updated ACS
Guidelines (including ACC/AHA,
Aspirin should be given to all patients without contraindications
at an initial loading dose of 150300 mg, and at a maintenance
dose of 75100 mg daily long-term regardless of treatment
strategy.

A P2Y12 inhibitor should be added to aspirin as soon as possible

and maintained over 12 months, unless there are
contraindications such as excessive risk of bleeding.

Clopidogrel Ticagrelor Prasugrel*

1.Kolh P et al. Eur Heart J August 29 2014; DOI:10.1093/eurheart/ehu278 [Epub ahead of print]

*Not yet approved and available in

2.Steg PG et al. Eur Heart J 2012;33:25692619; 3.Hamm CW et al. Eur Heart J 2011;32:2999 3054. 4. Amsterdam EA et al. J Am Coll Cardiol Sept 23, 2014 Epub ahead of
print. DOI:10.1016/j.jack.2014.09.017

Indonesia
7
 Profile P2Y12 inhibitor

Profile Clopidogrel Ticagrelor

Class Thienopyridine Triazolopyrimidine

Reversibility Irreversible Reversible

Activation Pro drug Active Drug

Adapted from Hamm CW et al. Eur Heart J 2011;32:2999 3054

Antiplatelet based on treatment approach

Acute coronary
syndrome
UA / NSTEMI STEMI

Medical PCI Fibrinolytic Primary PCI

Management
Ticagrelor Clopidogrel Ticagrelor
Ticagrelor Prasugrel* Prasugrel*
Clopidogrel Clopidogrel Clopidogrel

* Prasugrel is not yet approved and available in Indonesia

Roffi M et al. European Heart Journal 2015. doi:10.1093/eurheartj/ehv320; Steg PG et al. Eur Heart J
2012;33:25692619
9
 Dosage Antiplatelet
Antiplatelet Loading dose Maintenance dose Length of
treatment
Aspirin 325 mg 75 100 mg Indefinitely
Clopidogrel
PCI 600 mg 75 mg once daily 12 month
Medically Managed 300 mg 75 mg once daily 12 month

Ticagrelor
PCI 12 month
180 mg 90 mg twice daily
Medically Managed

Steg PG et al. Eur Heart J 2012;33:25692619; 3.Hamm CW et al. Eur Heart J 2011;32:2999 3054
 Controversies in DAPT
Dual Antiplatelet Aspirin + P2Y12 inhibitor
(Clopidogrel,Prasugrel or Ticagrelor) is a default
strategy in ACS patients undergoing PCI or Medically
managed, but still there are several issues that still
debatable :

1. Personalized DAPT
2. Timing of P2Y12 inhibitor administration
3. Duration of DAPT - Short term vs
prolong (beyond 12 months)
 DAPT STUDY
Dual Antiplatelets Therapy beyond one Year
After Drug-Eluting Coronary Artery Stent Procedures
Author | 00 Month Year Set area descriptor | Sub level 1 14
Author | 00 Month Year Set area descriptor | Sub level 1 15
PEGASUS-TIMI 54

A randomised, double-blind, placebo-controlled,

parallel-group, multinational trial to assess the
prevention of thrombotic events with ticagrelor
compared with placebo on a background of
acetylsalicylic acid therapy in patients with a
history of myocardial infarction
 PEGASUS-TIMI 54: Study Design
Patients aged 50 years with a history of spontaneous MI 13 years prior
to enrolment AND at least one additional atherothrombosis risk factor*
(N=21,162)

Ticagrelor 90 mg bid Ticagrelor 60 mg bid Placebo

+ ASA 75150 mg/day + ASA 75150 mg/day + ASA 75150 mg/day

Minimum of 12 months follow up:

Every 4 months in Year 1,
then semi-annually

Primary efficacy endpoint: CV death, MI or stroke

Primary safety endpoint: TIMI-defined major bleeding

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

Bonaca MP et al. Am Heart J 2014;167:437444

Bonaca MP et al. N Engl J Med 2015 [Epub ahead of print]
PEGASUS-TIMI 54: Primary Endpoint

10 Placebo 9.04% Placebo

Ticagrelor 90 mg bid
9 Ticagrelor 60 mg bid

8 7.85% 90 mg bid

7
Event rate (%)

7.77% 60 mg bid

3
Ticagrelor 90 mg vs placebo
HR 0.85 (95% CI 0.750.96) P=0.008
2
Ticagrelor 60 mg vs placebo
1 HR 0.84 (95% CI 0.740.95) P=0.004

0
0 3 6 9 12 15 18 21 24 27 30 33 36

No. at risk Months from randomisation

Placebo 7067 6979 6892 6823 6761 6681 6508 6236 5876 5157 4343 3360 2028
90 mg bid 7050 6973 6899 6827 6769 6719 6550 6272 5921 5243 4401 3368 2038
60 mg bid 7045 6969 6905 6842 6784 6733 6557 6270 5904 5222 4424 3392 2055

CI, confidence interval; HR, hazard ratio

Bonaca MP et al. N Engl J Med 2015 [Epub ahead of print]

 PEGASUS-TIMI 54: Bleeding
5

4 Ticagrelor 90 mg bid
Ticagrelor 60 mg bid
3-year KM event rate

P<0.001
Placebo
3
2.6
2.3
P<0.001
2
P=NS P=NS P=NS
1.3
1.1 1.2
1
0.6 0.7 0.6 0.6
0.6 0.5
0.4 0.3 0.3
0.1
0
TIMI major TIMI minor Fatal bleeding ICH Fatal bleeding
bleeding bleeding or ICH

Rates are presented as 3-year Kaplan-Meier estimates

P<0.026 indicates statistical significance
Bonaca MP et al. N Engl J Med 2015 [Epub ahead of print]
Bittl JA, et al. JACC 2016.
Systematic Review
for the 2016 ACC/AHA
Guideline Focused Update
on Duration of DAPT
Patients With CAD
Bittl JA, et al. JACC 2016.
Systematic Review for the
2016 ACC/AHA Guideline
Focused Update on
Duration of Dual
Antiplatelet Therapy in
Patients With Coronary
Artery Disease.
 2015 ESC Guidelines NSTEACS

1A
P2Y12 inhibitor is recommended, in addition to aspirin, for 12
months unless there are contraindications such as excessive risk
of bleeds

Ticagrelor is recommended, in the absence of

contraindications,for all patients at moderate-to-high risk of
ischaemic events (e.g. elevated cardiac troponins), regardless of 1B
initial treatment strategy and including those pretreated with
clopidogrel

Prasugrel is recommended in patients who are proceeding to

PCI if no contraindication. 1B
Clopidogrel is recommended for patients who cannot receive
ticagrelor or prasugrel or who require oral anticoagulation. 1B
Roffi M et al. Eur Heart Journal 2015. doi:10.1093/eurheartj/ehv320
 2014 ESC Guidelines Myocardial
Revascularization STEMI PCI
A P2Y12 inhibitor is recommended in addition to ASA and
maintained over 12 months unless there are contraindications
such as excessive risk of bleeding. Options are:
1A
1B
Prasugrel (60 mg loading dose, 10 mg daily dose) if no
contraindication

1B
Ticagrelor (180 mg loading dose, 90 mg twice daily) if no
contraindication

Clopidogrel (600 mg loading dose, 75 mg daily dose), only when

prasugrel or ticagrelor are not available or are contraindicated. 1B
1B
It is recommended to give P2Y12 inhibitors at the time of first
medical contact.
2016 ACC/AHA Guideline Focused Update
on Duration DAPT
Summary

Antiplatelet plays an important role in ACS

Management
Dual Antiplatelet treatment is a standard
treatment in ACS
Updated guidelines has recommended
ticagrelor as 1st line treatment in ACS ,
preferred over clopidogrel
Choose the right P2Y12 inhibitor by considering
ischemic risk and bleeding risk ACS patient