Latest Pharmacoteraphy in ACS

Dr Nurwahyudi, SpJP

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 Acute Coronary Syndrome
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. EurHeart J 2011;32:2999 –3054 3

Spectrum ACS
 Chest pain

ST elevation ST depression
ECG ST segment

Bio-chemistry Troponin rise / Troponin

fall normal

Diagnosis
UA
NSTEMI
STEMI

Adapted from Hamm CW et al. Eur Heart J 2011;32:2999 – 3054, Davies MJ. Heart 2000;83:361–366 5
 STEMI Management : Primary PCI or Fibrinolytic

Reference: 1. Ibanez B et al. European Heart Journal 2017; 00; 1–66 6

 NSTEACS Management
strategy
Step 1. initial evaluation

Step 2. Diagnosis validation, risk assessment

and rhythm monitoring

Step 3. invasive strategy

Step 4. revascularization modalities

Step 5. hospital discharge

and post-discharge management

Roffi M et al. European Heart Journal 2015. doi:10.1093/eurheartj/ehv320 7

 Symptom Onset

FMC  NSTE-ACS Diagnosis

PCI Centre Non PCI Centre

Immediate transfer to PCI centre
Very High Very High
Risk Stratification

Same day transfer

High High

Transfer
Intermediate Intermediate
Transfer
Optional
Low Low
Therapeutic Strategy

Immediate Non-invasive
invasive Early invasive invasive testing if
(< 2hr) (< 24hr) (< 72hr) appropriate
Pharmacotheraphy
 Pharmacoterapy in ACS

• Fibrinolityc therapy
• Antiplatelet
• Anticoagulant
• Anti Ischemia
• Adjunctive Therapy
Pharmacotherapy

Ischemia:
Nitrat
Beta Blocker

Bleeding:
Anti Coagulant
Anti platelet
Fibrinolitic
 Initial Treatment

Roffi M et al. Eur Heart J 2016;37(3):267-315; Hamm CW et al. Eur Heart J 2011;32:2999 – 3054
 Activated platelets are central to
thrombus formation in ACS
• Platelets do 3 things that promote thrombus
formaton Activated platelets aggregate
and assemble a critical mass
– Adhesion 3 of activated, pro-thrombotic
platelet membrane at the site
– Activation of injury

– Aggregation
Adherent platelet become activated
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1
Plaque rupture leads
to platelet adhesion
to the exposed
subendothelium

Vorchheimer DA, et al. Mayo Clin Proc. 2006;81:59-68; Davies MJ. Heart. 2000;83:361-366.
 STEMI 2017 - Primary PCI
Ticagrelor preferred before clopidogrel
• The goal of antiplatelet therapy is to provide maximal protection
against thrombosis without increasing the risk of bleeding

• Risk of stent thrombosis for patient undergoing PCI

Recommendations Class Level

Guideline
Antiplatelet therapy
A potent P2Y12 inhibitor (prasugrel or
NEW ticagrelor), or clopidogrel if these are not
available or are contraindicated, is
ESC
recommended before (or at latest at the time I A
20171
of) PCI and maintainded over 12 months,
unless there are contraindications such as
excessive risk of bleeding.

* Prasugrel is not yet approved and available in Indonesia

Bode C and Huber K. European Heart Journal Supplements. 2008: 10 (Supplement A), A13–A20; Steg PG et al. Eur Heart J 2012;33:2569–
2619; 1. Ibanez B et al. European Heart Journal 2017; 00; 1–66 15
 ESC STEMI Guidelines 2017
Recommendation on Fibrinolytic Therapy
Recommendations Class Level
Antiplatelet therapy
When fibrinolysis is the reperfusion strategy, it is recommended to initiate
this treatment as soon as possible after STEMI diagnosis, preferably in the I A
pre-hospital setting
A fibrin-specific agent (i.e. tenecteplase, alteplase, or reteplase) is
I B
recommended.
Antiplatelet co-therapy with fibrinolysis

Oral or i.v. aspirin is indicated I B

Clopidogrel is indicated in addition to aspirin I A

DAPT (in the form of aspirin plus a P2Y12 inhibitor #) is indicated for up to 1
I C
year in patients undergoing fibrinolysis and subsequent PCI.

#Clopidogrel is the P2Y12 inhibitor of choice as co-adjuvant and after fibrinolysis, but 48 h
after fibrinolysis, switch to prasugrel/ticagrelor may be considered in patients who underwent
PCI

Reference: 1. Ibanez B et al. European Heart Journal 2017; 00; 1–66. 2. Windecker S. et al European Heart J. 2014; 1-12
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Fibrinolytic Therapy

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 ESC NSTEACS 2015
Ticagrelor preferred before clopidogrel
• The time course of events following presentation with NSTE-ACS
necessitates immediate treatment with antiplatelet therapy,
once the diagnosis is made
• Antiplatelet therapy is necessary for the acute event, and
subsequent maintenance therapy
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 1B
of initial treatment strategy and including those pretreated with
clopidogrel (which should be discontinued when ticagrelor is
started).

Clopidogrel is recommended for patients who cannot receive

ticagrelor or prasugrel or who require oral anticoagulation. 1B

*Prasugrel is not yet approved and available in Indonesia

Hamm CW et al. Eur Heart J 2011;32:2999 – 3054; Amsterdam EA et al. J Am Coll Cardiol Sept 23, 2014 Epub ahead of print.
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DOI:10.1016/j.jack.2014.09.017; Kolh P et al. Eur Heart J August 29 2014; DOI:10.1093/eurheart/ehu278 [Epub ahead of print]

Primary PCI
• Anticoagulation is
recommended for all
patients in addition to
antiplatelet therapy during
primary PCI (1C)
• Routine use of UFH is
recommended (1C)
• Routine use of enoxaparin
i.v. should be
• Considered (IIaA)
• Fondaparinux is not
recommended for primary
PCI (IIIB)
Anticoagulant
Fibrinolytic Therapy
• Anticoagulation is recommended
in patients treated with lytics until
revascularization (if performed)
or for the duration of hospital
stay up to 8 days.(1A)
• Enoxaparin i.v. followed by s.c.
(preferred over UFH) (1A)
• UFH given as a weight-adjusted
i.v. bolus followed by infusion
(1B)
• In patients treated with
streptokinase: fondaparinux i.v.
bolus followed by an s.c. dose 24
h later (IIaB)
NSTEACS
• Fondaparinux (2.5 mg s.c. daily) is
recommended as having the most
favourable efficacy–safety profile
regardless of the management strategy.
(1B)
• Enoxaparin (1 mg/kg s.c. twice daily) or
UFH are recommended when
fondaparinux is not available. (1B)
• Enoxaparin should be considered as an
anticoagulant for PCI in patients
pretreated with s.c. enoxaparin. (IIaB)
• UFH 70–100 IU/kg i.v. (50–70 IU/kg if
concomitant with GPIIb/IIIa inhibitors) is
recommended in patients undergoing PCI
who did not receive any anticoagulant.
(1B)
• In patients on fondaparinux (2.5 mg s.c.
daily) undergoing PCI, a single i.v. bolus
of UFH (70–85 IU/kg, or 50– 60 IU/kg in
the case of concomitant use of GPIIb/IIIa
inhibitors) is recommended during 19 the
procedure (1B)
 Adjunctive Treatment

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STEMI Patients
STEMI Patients
STEMI Patients
Adjunctive Treatment in NSTEACS
It is recommended to start
high-intensity statin therapy as early as
possible, unless contraindicated, and
maintain it long term.
An ACE inhibitor is recommended in
patients with LVEF ≤40% or heart
failure, hypertension or diabetes,
unless contraindicated

An ARB provides an alternative,

particularly if ACE inhibitors are not
tolerated.

Beta-blocker therapy is recommended

in patients with LVEF ≤40%, unless
contraindicated.

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