This document discusses antiplatelet therapy for acute coronary syndromes. It provides information on dual antiplatelet therapy using aspirin and P2Y12 inhibitors like clopidogrel, prasugrel, and ticagrelor. It summarizes trials comparing these drugs and outlines treatment strategies and duration of dual antiplatelet therapy based on a patient's risk level. Factors influencing response to clopidogrel and the potential additional mechanisms of action of ticagrelor are also reviewed.

1. Magdy El-Masry.
Prof. of Cardiology.
Tanta University.

2. Initial assessment of patients with suspected acute coronary syndromes
“Other cardiac” includes, among other, myocarditis, Tako-Tsubo cardiomyopathy, or
tachyarrhythmias.
“Non-cardiac” refers to thoracic diseases such as pneumonia or pneumothorax.
If the initial evaluation suggests aortic dissection or pulmonary embolism, D-dimers and
MDCT angiography are recommended

3. STEMI time delays (Time is Myocardium ) “You may delay, but
time will not, and lost time is never found again.”
Patient Delay System Delay
FMC
door-to-balloon time
door-to-needle time

4. Selection of NSTE-ACS treatment strategy and
timing according to initial risk stratification.

5. Dual Anti-Platelet Therapy (DAPT)

6. Pathophysiology of ACS: The Role of Platelets

8. Comparative pharmacokinetics of
oral P2Y12 inhibitors.
Time to
peak
platelet
inhibition

9. Available P2Y12 blockers
DAPT (ASA + clopidogrel/prasugrel/ticagrelor)
is recommended after ACS (STEMI or NSTE-ACS) to reduce
the risk of thrombosis

10. Factors linked to clopidogrel response
variability. Thromb Haemost 2015; 113: 37–52

11. Figure 3. Conceptualizeddistinctionbetween pharmacological response to therapy and
treatment failures.
Michelle O’Donoghue, and Stephen D. W iviott Circulation.
2006;114:e600-e606
Copyright © American Heart Association, Inc. All rights reserved.

12. PLATelet inhibition and patient Outcomes (PLATO) trial.
Ticagrelor vs clopidogrel in patients with acute coronary syndromes.
Acute Stroke Or Transient IsChaemic Attack TReated With
Aspirin or Ticagrelor and Patient OutcomES"SOCRATES"

13. The PLATO Trial (Ticagrelor vs Clopidogrel)
1998
2011

16. All-cause death in the ticagrelor and clopidogrel arms of the PLATO trial.
Percentages are Kaplan–Meier estimates of the rate of the endpoint at 12
months. Mortality rates are reported in the overall population, in subgroups of
patients undergoing either planned invasive or conservative strategy

18. Canadian Journal
of Cardiology 29
(2013) 1334-1345
Based on the PLATO results, the 2012 Canadian Cardiovascular Society
Antiplatelet Guidelines recommend the following:

19. *Moderate to high-risk NSTEACS as defined in PLATO : ≥ 2 of: (1) ischemic ST changes on
electrocardiogram; (2) positive blomarkers; and (3) 1 of the following: 60 years of age or greater,
previous MI or CABG, CAD > 50% stenosis in 2 vessels, previous ischemic stroke, diabetes, peripheral
arterial disease, or chronic renal dysfunction.

20. * Prasugrel should be avoided in patients with previous TIA or stroke. In patients aged 75 years and older,
or body weight ≤ 60 kg, prasgurel should be used with caution and a 5 mg dose considered.

21. Administration of oral P2Y12 inhibitors prior to coronary angiography has
long been the gold standard in patients with ACS.
The aim of such a strategy was to allow stent implantation to be
performed at a time when platelet activation was reduced to
prevent ischemic complications and avoid early stent thrombosis.
Pretreatment would also reduce pre-PCI ischemic events by reducing
thrombotic burden.

24. Initiating Antiplatelet Therapy In Patients With ACS
Making decisions in the ER or
Cath lab when time matters
Loading ticagrelor in patients with ACS is not restricted by

26. Ticagrelor is a faster and more potent P2Y12 inhibitor that
demonstrated a significant clinical benefit over clopidogrel in ACS.
It is therefore recommended as a first-line agent over
clopidogrel in ACS
Caution in those with a history of COPD,
asthma, HF, gout & severe renal impairment due to increased
risk of dyspnea & elevated serum uric acid & creatinine.

27. Interplay between ticagrelor and adenosine in humans including impact on the
heart, lungs, and brain (top); intestine (middle); platelets,kidneys, and liver
(bottom). A1, A2A, A2B, and A3 are adenosine receptors potentially involved.
Pleiotropic effects of ticagrelor

28. Ticagrelor
inhibits
cellular
uptake of
adenosine
Formation of adenosine and its intracellular uptake and metabolism, which are reduced
by ticagrelor through inhibition of ENT1(equilibrative nucleoside transporter 1)
Does ticagrelor have additional mechanism(s) of action?

29. Potential underlying mechanisms of ticagrelor’s offtarget effects.

30. =

31. Antiplatelet therapy post-ACS
The clinical cardiologist’s role
What is the optimal duration of DAPT after ACS?
 Duration of DAPT in Patients With ACS Treated With Medical Therapy Alone
 Duration of DAPT in Patients With STEMI Treated With Fibrinolytic Therapy
 Duration of DAPT in Patients With ACS Treated With PCI
 Duration of DAPT in Patients With ACS Treated With CABG

32. Balanced Benefit/Risk Ratio
Sweet spot
Ischemic
Risk
Bleeding
Risk

36. This study identified a sub-group of patients at high risk of
recurrent ischemic events that occurred more than 12
months after an initial MI who could benefit from
prolonged DAPT by aspirin and ticagrelor.
(Prevention of
Cardiovascular Events in
Patients With Prior Heart
Attack Using Ticagrelor
Compared to Placebo on
a Background of Aspirin)
trial

37. DAPT Risk Score Picks
Patients for Extended
Therapy
'This is exactly what we
need' to balance benefit
and risk
Continuation of DAPT beyond 1 year reduces the risk of MI and
stent thrombosis, with the tradeoff of increased bleeding.

38. Using the DAPT Score to Predict
Stent Thrombosis vs. Bleeding

41. Master Treatment Algorithm for Duration of P2Y12 Inhibitor
Therapy in Patients With CAD Treated With DAPT

42. Treatment Algorithm for Duration of P2Y12Inhibitor Therapy in
Patient With Recent ACS (NSTE-ACS or STEMI)