This document summarizes a randomized controlled trial that compared clopidogrel to ticagrelor or prasugrel in 1002 patients aged 70 years or older with non-ST-elevation acute coronary syndrome. Patients were randomly assigned to receive clopidogrel or ticagrelor/prasugrel. The primary outcome was major or minor bleeding, while the co-primary outcome included mortality, myocardial infarction, stroke, and bleeding. The results found clopidogrel was associated with fewer bleeding events compared to ticagrelor/prasugrel without increasing the risk of the combined clinical outcome. The conclusion is that clopidogrel could be an alternative P2Y12 inhibitor, especially for elderly patients

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2. Clopidogrel versus Ticagrelor or Prasugrel
in patients aged 70 years or older
with non-ST-elevation acute coronary syndrome {NST ACS}
(POPular AGE)
DR PRATAP SANDIPANRAO LENDAL
JUNIOR RESIDENT
DEPARTMENT OF MEDICINE
VDGIMS LATUR

3. Index
1. Introduction to antiplatelet drugs
2. Classification
3. Individual drugs
4. About article
5. Conclusion

4. Introduction
Normal hemostasis
1. Maintenance of blood in a
fluid ,clot-free state in
normal vessel
2. Formation of hemostatic
plug at a site of vascular
injury
3. In normal hemostasis
Thrombi are lysed and blood
is made fluid by fibrinolytic
system

5. • Hemostasis and
thrombosis are
regulated by three
general
components
1. The vascular
wall
2. Platelets
3. The coagulation
cascade

6. • Receptors on platelets:
– GpIa/IIa: receptors for
collagen
– GpIb: receptor for vWF
– GpIIb/IIIa: receptor for
fibrinogen
– P2Y1 /P2Y12: receptors for
ADP
– PAR1/PAR4: receptors for
thrombin (IIa)
PLATELETS

7. • Platelets provide the initial
Hemostatic Plug at sites of
vascular injury
• They also participate in
Pathological Arterial
Thrombosis that lead to
myocardial infarction, stroke,
and peripheral vascular
thromboses
How platelets work

8. Classification
TXA2
Inhibitors
Phospohodie
sterase
inhibitors
Thienopyri
dine
derivatives
Glycoprotein
(GP) IIb/IIIa
Inhibitor
Newer
antiplatelet
Aspirin(no
n
Selective/ir
reversible)
Dipyridamole Ticlopidine Abciximab Cangrelor
Clopidogre
l
Eptifibatide Ticagrelor
Prasugrel Tirofiban

9. Individual drugs
•Clopidogrel
•Ticagrelor
•Prasugrel

10. Clopidogrel
• Theinopyridine pro drug with slow onset of action (only
15% is activated by CYP3A4)
• Irreversible inhibitor of platelet P2Y12
• More potent and lesser side effects
• Usual dose is 75 mg/day with or without an initial loading
dose of 300 or 600 mg

11. Benefits
• Secondary prevention of stroke : somewhat better than
aspirin
• Prevention of recurrent ischemia in patients with unstable
angina: better as combination with aspirin
• Synergistic with aspirin since mechanism of action is
different

12. Pharmacology
• Wide inter-individual variability in efficacy of
clopidogrel is seen
• Genetic polymorphism in CYP2C19
• Patients with reduced function of CYP2C19*2 allele
show less inhibition of platelets by clopidogrel and
have higher rate of cardiovascular events

13. Uses
• To reduce the rate of stroke, myocardial infarction,
and death in
– Patients with recent myocardial infarction or stroke
– Established peripheral arterial disease
– Acute coronary syndrome

14. Interactions
• Proton pump inhibitors, inhibitors of CYP2C19,
produce a small reduction in the inhibitory effects of
clopidogrel on ADP induced platelet aggregation

15. Prasugrel
• Thienopyridine prodrug
• Rapid onset of action
• Greater inhibition of ADP induced platelet aggregation
• Almost completely absorbed from the gut
• Almost all of the drug is activated

16. • Irrversible inhibitor of P2Y12 receptor
• Has prolonged effect after discontinuation
• Better than clopidogrel in reducing incidence of
non fatal MI
• The incidence of stent thrombosis also was lower with
prasugrel than with clopidogrel

17. • However, it has higher rates of fatal and life threatening
bleeding
• Contraindicated in those with a history of
cerebrovascular disease - high risk of bleeding
• Caution is required if prasugrel is used in patients
weighing <60 kg or in those with renal impairment

18. • After a loading dose of 60 mg, prasugrel is given once
daily at a dose of 10 mg
• Patients >75 years of age or weighing <60 kgmay do better
with a daily prasugrel dose of 5 mg
• It is reasonable alternative to clopidogrel in patients with
the loss-of-function CYP2C19 allele because there is no
association with decreased anti platelet action in prasugrel

19. Ticagrelor
• Orally active reversible inhibitor of P2Y12 receptor
• Rapid onset and offset of action
• Twice daily dosage
• First new antiplatelet drug to demonstrate a reduction in
cardiovascular death compared with clopidogrel in patients
with acute coronary syndromes

20. About study
•Background
•Methods
•Participants
•Randomisation
•Procedures
•Outcome
•Results
•Discussion
•Conclusion

21. Background
Current guidelines recommend potent platelet inhibition
with ticagrelor or prasugrel in patients after an acute
coronary syndrome. However, data about optimal platelet
inhibition in older patients are scarce.
We aimed to investigate the safety and efficacy of
clopidogrel compared with ticagrelor or prasugrel in older
patients with non-ST-elevation acute coronary syndrome
(NSTE-ACS)

22. Methods
•Open-label, Randomised controlled [POPular AGE] trial in 12
sites in Netherlands
•Patient and treating physicians were aware of the allocated
treatment strategy, but the outcome assessors were masked to
treatment allocation.
• Follow-up duration was 12 months.
• Analyses were done on intention-to-treat basis.
• This trial is registered with the NetherlandsTrial Register
(NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT
(2013–001403–37).

23. Participants
Patients having
•non ST elevation acute coronary syndrome
•Age 70 years or older
Exclusion criterion
•ST elevation ACS
•Age less than 70

24. Randomissation
randomly assigned in a 1:1 ratio using an internet-based
randomisation procedure with block sizes of six

25. Procedure
clopidogrel ticagrelor prasugrel
Loading dose 300/600 mg 180 mg 60 mg
Maintainance
[12months]
75 mg od 90 mg bd 10 mg od

26. Outcomes
Primary bleeding outcome
1. Platelet inhibition
2. Patient Outcomes (PLATO; major or minor bleeding
[superiority hypothesis])
Co-primary net clinical outcome consisted of
1. Mortality
2. myocardial infarction
3. Stroke
4. PLATO major and minor bleeding (non-inferiority hypothesis,
margin of 2%)

27. Results
Between June 10, 2013, and Oct 17, 2018, 1002 patients
were randomly assigned to clopidogrel (n=500) or ticagrelor
or prasugrel (n=502)
clopidogrel Ticagrelor/prasugrel
Total 500 502
Premature
discontinuation
112[22%] 238[47%]
Primary bleeding
outcome
88[18%] 118[24%]
Co-primary outcome 139[28%] 161[32%]

28. Conclusion
In patients aged 70 years or older presenting with NSTE-
ACS, clopidogrel is a favourable alternative to ticagrelor,
because it leads to fewer bleeding events without an
increase in the combined endpoint of all-cause death,
myocardial infarction, stroke, and bleeding.Clopidogrel
could be an alternative P2Y12 inhibitor especially for elderly
patients with a higher bleeding risk.

29. Bibliography
•1.Wallentin L ..Becker RC .BudajA .et al.
Ticagrelor versus clopidogrel in patients with acute coronary syndromes.
N Engl J Med. 2009; 361: 1045-1057Eur Heart J. 2016; 37: 267-31
•2.Valgimigli M..Bueno H ..Byrne RA .et al.
2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in
developed in collaboration with EACTS.
Eur Heart J. 2018; 39: 213-260
•3.Wiviott SD .Braunwald E .McCabe CH .et al.
Prasugrel versus clopidogrel in patients with acute coronary syndromes.
N Engl J Med. 2007; 357: 2001-2015

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