- The document discusses guidelines for antiplatelet therapy before, during, and after hospitalization for acute coronary syndrome (ACS). - It recommends aspirin for all patients without contraindications, and ticagrelor over clopidogrel or prasugrel due to its greater effectiveness in reducing ischemic events, stent thrombosis, and death for up to one year. - For patients undergoing percutaneous coronary intervention (PCI), pretreatment with a P2Y12 inhibitor such as clopidogrel is recommended to reduce complications, with higher loading doses for those who have not received previous treatment.

1. Antiplatelet therapy-
Before, during and after
hospitalization for ACS
Dr Akshay Mehta
Asian Heart Institute
Nanavati Superspeciality Hospital

2. A 62 year old gentleman develops typical chest
pain at home. What drug(s) should he take on
the way to the hospital ?
• Chewable aspirin 325 mg
• Enteric coated aspirin 325 mg
• Chewable aspirin 75 mg with ticagrelor 180 mg
• Chewable aspirin 325 mg with clopidogrel 300 mg

3. If it turns out to be a case of NSTE-ACS in the
hospital with ST changes and raised Troponins.
when & which P2Y12 inhibitor you will advise?
A. On diagnosis, 300 mg clopidogrel
B. In cath lab, before PCI 600 mg clopidogrel
C. On diagnosis, 60 mg prasugrel
D. On diagnosis, 180 mg ticagrelor
E. In cath lab, before PCI 180 mg ticagrelor

6. In the TRILOGY ACS trial, comparing prasugrel with clopidogrel,
prasugrel _____ the incidence of the primary efficacy endpoint
(composite of cardiovascular death, MI, or stroke) in patients age
< 75 years.
• Significantly increased
• Significantly decreased
• Had no significant effect on
Answer: Had no significant effect on
In the TRILOGY ACS trial, patients with ACS were eligible if they were selected for a final
treatment strategy of medical management without revascularization within 10 days of
the index event. Patients were randomized to receive either prasugrel or clopidogrel. The
primary efficacy endpoint was a composite of cardiovascular death, MI, or stroke among
patients under the age of 75 years. Patients were evaluated up to 30 months. At 30
months, there was no significant between-group difference in the rate of the primary
efficacy endpoint; the primary endpoint occurred in 13.9% of the prasugrel group and
16.0% of the clopidogrel group (HR 0.91; 95% CI 0.79-1.05; P = .21). Prasugrel is not
recommended in clinical practice guidelines in patients managed without PCI (ie, not
recommended in patients managed conservatively/medically).

7. Clopidogrel No
Trial Pretreatment Pretreatment
PCI-CURE 3.6 5.1
CREDO n/a n/a
PCI-CLARITY 4.0 6.1
Overall 3.7 5.5
Clopidogrel No
Trial Pretreatment Pretreatment
PCI-CURE 2.9 4.4
CREDO 6.0 7.1
PCI-CLARITY 3.3 5.4
Overall 3.9 5.5
Meta-Analysis of Clopidogrel Pretreatment
1.00.25 2.00.5
1.00.25 2.00.5
OR (95% CI)
OR (95% CI)
CV Death or MI after PCI (%)
MI before PCI (%)
OR 0.67
P=0.005
Favors
Pretreatment
Favors
No Pretreatment
OR 0.71
P=0.004
Sabatine MS et al. JAMA 2005;294:1224-32

8. PLATO study design
Primary endpoint: CV death + MI + Stroke
Primary safety endpint: Total major bleeding
6–12-month exposure
Clopidogrel
If pre-treated, no additional loading dose;
if naive, standard 300 mg loading dose,
then 75 mg qd maintenance;
(additional 300 mg allowed pre PCI)
Ticagrelor
180 mg loading dose, then
90 mg bid maintenance;
(additional 90 mg pre-PCI)
NSTE-ACS (moderate-to-high risk) STEMI (if primary PCI)
Clopidogrel-treated or -naive;
randomised within 24 hours of index event
(N=18,624)
PCI = percutaneous coronary intervention; ASA = acetylsalicylic acid;
CV = cardiovascular; TIA = transient ischaemic attack

9. Conclusions
• Reversible, more intense P2Y12 receptor inhibition for one year with
ticagrelor in comparison with clopidogrel in a broad population with
ST- and non-ST-elevation ACS provides
– Reduction in myocardial infarction and stent thrombosis
– Reduction in cardiovascular and total mortality
– No change in the overall risk of major bleeding
Ticagrelor is a more effective alternative than clopidogrel
for the continuous prevention of ischaemic events, stent
thrombosis and death in the acute and long-term treatment
of patients with ACS

10. Recommendations for platelet inhibition in non-
ST elevation ACS
-2015 ESC guidelines on UA/NSTEMI
• Aspirin for all without contraindications
• Ticagrelor (180 mg loading dose, then 90 mg twice daily) in the
absence of contraindications regardless of initial treatment
strategy for all patients at moderate-to-high risk of ischaemic
events (e.g. elevated cardiac troponins),and including those
pretreated with clopidogrel
• Prasugrel (60 mg loading dose, 10 mg daily dose) is recommended
ONLY in patients who are proceeding to PCI if no contraindication
• Clopidogrel (300–600 mg loading dose, 75 mg daily dose) is
recommended for patients who cannot receive ticagrelor or
prasugrel or who require oral anticoagulation.

11. A 74 years age man enters ER with chest pain of 2 hours’
duration. ECG shows acute anterior wall STEMI. He is a
diabetic without h/o stroke, bleed or TIA in past. Family
has yet to decide about primary PCI. What antiplatelet
besides aspirin will you advise the ER to give & at what
dosage ?
• Clopidogrel 300 mg
• Ticagrelor 180 mg
• Prasugrel 60 mg
• Clopidogrel 600 mg

12. Adjunctive Antithrombotic Therapy to Support
Reperfusion With Fibrinolytic Therapy
2013 ACCF/AHA STEMI guidelines

13. After taking 300 mg of clopidogrel,
he opts for PCI. What additional
antiplatelet drug will you advise ?
• 300mg more of clopidogrel
• 180 mg of ticagrelor
• 60 mg of prasugrel
• Nothing

15. An 78 year old gentleman opts for
fibrinolysis for an acute MI.
Besides aspirin, the other antiplatelet
drug advisable before lytic therapy is :
• Clopidogrel loading dose of 300 mg
• Clopidogrel 75 mg
• Ticagrelor half loading dose of 90 mg
• Prasugrel half loading dose of 30 mg

16. It is beneficial to give Ticagrelor, pre
hospital in ambulance in a case of
acute STEMI and decided to be taken
up for primary PCI.
• True
• False

19. Definite Stent Thrombosis up to 30 Days after Ticagrelor
Administration in the Modified Intention-to-Treat Population.
Montalescot G et al. N Engl J Med 2014;371:1016-
1027.

22. In the TRITON-TIMI 38 trial, a post-hoc analysis revealed that
favorable net clinical benefit was observed with prasugrel versus
clopidogrel only in:
A. Patients with and without prior stroke/TIA
B. Patients without prior stroke/TIA
C. Patients weighing < 60 kg
D. Patients age ≥ 75 years
E. Patients without prior stroke/TIA, weight ≥ 60 kg and age ≤75 years
Answer: Patients without prior stroke/TIA
In the TRITON-TIMI 38 trial, a series of post-hoc exploratory analyses were
performed to identify the subgroups of patients who did not have a favorable net
clinical benefit (defined as the rate of death from any cause, nonfatal MI, nonfatal
stroke, or non-CABG-related nonfatal TIMI major bleeding) from the use of
prasugrel or who had net harm. Patients who had a previous stroke or TIA had net
harm from prasugrel (HR 1.54, 95% CI 1.02-2.32). Therefore, the prescribing
information for prasugrel indicates that prasugrel should not be used in patients
with a history of TIA or stroke. Patients 75 years of age or older had no net benefit
from prasugrel (HR 0.99, 95% CI 0.81-1.21), and patients weighing less than 60 kg
had no net benefit from prasugrel (HR 1.03, 95% CI 0.69-1.53). Patients without
prior stroke/TIA, < 75 years, and weighing ≥ 60 kg had a favorable net clinical
benefit from the use of prasugrel versus clopidogrel.

23. A patient of ACS has undergone
angiography and has to undergo CABG.
Which DAPT combination would have
been the best for him ?
A. Clopidogrel with aspirin
B. Prasugrel with aspirin
C. Ticagrelor with aspirin

25. A patient of ACS on DAPT has to undergo elective
CABG. Assuming different DAPT combinations going on,
when to stop which drug before the surgery ?
A. Stop aspirin and clopidogrel (3 days before)
B. Stop Ticagrelor alone (7 days before) & ct aspirin
C. Stop Clopidogrel alone (5 days before) & ct aspirin
D. Stop Prasugrel alone (5 days before) & ct aspirin

26. Antiplatelets at time of CABG:
2014 ACC/AHA UA/NSTEMI
• Initiate and continue ASA
• Discontinue clopidogrel/ticagrelor 5 days before,
and prasugrel 7 days before ELECTIVE CABG
• Discontinue clopidogrel/ticagrelor Upto 24 hrs before urgent
CABG.
• May perform urgent CABG<5 days after discontinuing
clopidogrel/ticagrelor, and < 7 days after discontinuing
prasugrel
• Discontinue eptifibatide/tirofiban at least 2-4 hrs before, and
abciximab ≥ 12 hrs before CABG

27. ESC/EACTS 2014

28. Which dose of aspirin is better for
long term use ?
• 75 to 150 mg
• 150 to 325 mg
• 325 mg

29. High- vs. low-dose aspirin comparison at long-term follow-up.
Sanjit S. Jolly et al. Eur Heart J 2009;30:900-907
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2008. For permissions please email: journals.permissions@oxfordjournals.org

30. Your 40 year old patient with diabetes
undergoes stenting of a large, very proximal LAD
for STEMI and is on aspirin & prasugrel. How
long will you continue them after PCI ?
A. Aspirin lifelong and prasugrel for 3 months
followed by clopidogrel for 9 more months
B. Both aspirin and prasugrel for 1 year and
then stop both
C. Aspirin lifelong and prasugrel for 12 months
± clopidogrel long term
D. Both aspirin and prasugrel life long

31. 2014 ESC/EACTS Revasc Guidelines
Post PCI
• STEMI/ NSTEMI : Any P2Y12 inhibitor is recommended in
addition to ASA, and maintained over 12 months unless there
are contraindications such as excessive risk of bleeding. (Class 1)
•
• SCAD : DAPT (with clopidogrel) is indicated for at least 1 month
after BMS implantation and for 6 months after DES implantation.
(both class 1)
• Shorter DAPT duration (<6 months) may be considered after DES
implantation in patients at high bleeding risk. (Class Iib)

32. In the DAPT study, dual antiplatelet therapy beyond 1 year after placement of a
drug-eluting stent, as compared with aspirin alone, resulted in _______ in the
composite of major adverse cardiovascular and cerebrovascular events and
____ in the risk of moderate or severe bleeding.
A. No difference, no difference
B. A decrease, no difference
C. No difference, an increase
D. A decrease, an increase
E. A decrease, a decrease
Answer: A decrease, an increase
In the DAPT study, the primary analysis cohort was randomized drug-eluting stent-
treated subjects. Continued treatment with dual antiplatelet therapy (aspirin plus a
thienopyridine in the DAPT study) for beyond 12 months reduced the rate of major
cardiovascular and cerebrovascular events (4.3% vs 5.9% with only 12 months of
dual therapy treatment; HR 0.71, 95% CI 0.59-0.85, P < .001). However, longer
duration of thienopyridine therapy was associated with a significant increase in
moderate or severe bleeding (2.5% vs 1.6%, P = .001).

33. A 62 years age male patient of stable angina on 75
mg daily aspirin only, gets admitted for PTCA. When,
which and what dose of antiplatelet drugs would
you advise to be taken ?
A. Clopidogrel 600 mg 2 hours before PTCA
B. Clopidogrel 300 mg 1 hour before PTCA
C. Prasugreal 60 mg just before PTCA
D. Ticagrelor 180 mg 2 hours before PTCA

34. 2014 ESC/EACTS Guidelines on myocardial
revascularization- antiplatelets during stenting
for Stable CAD
• ASA is indicated before elective stenting. (I B)
• ASA oral loading dose of 150–300 mg (or 80-150 mg
i.v.) is recommended if not pre-treated. (I C)
• Clopidogrel (600 mg loading dose or more, 75 mg
daily maintenance dose) is recommended for
elective stenting. (1A)
• GP IIb/IIIa antagonists should be considered only for
bail-out.(IIaC)

35. A pt on OAC for AF undergoes
PTCA. What antiplatelet therapy
would you recommend for him ?
• OAC +Aspirin + Clopidogrel for 12 months
• OAC +Aspirin + Clopidogrel for 1 month,
followed by OAC +Aspirin till 12 months
• OAC + Ticagrelor for 12 months
• Depends on clinical situation, bleeding risk,
clotting risk

36. Recommendations for antithrombotic treatment
in patients undergoing PCI who require oral
anticoagulation ESC/EACTS 2014

37. DAPT in pt with OAC for AF

38. One way to ensure faster action of
P2Y12 inhibitors is :
A. Administer clopidogrel by rectal suppository
B. Give prasugrel in liquid form
C. Crush ticagrelor and swallow with water

39. Aspirin + Clopidogrel v/s Ticagrelor
v/s Prasugrel
• Chest pain
• ACS A Non ACS
UA/NSTEMI T C STEMI C
(PCI or conservative)
Pr PCI T C Fibrinolysis C
Prasugrel- only at time of PCI in any ACS

40. Take Home……
• Aspirin for all, forever
• Only clopidogrel for fibrinolysis
• Ticagrelor , at diagnosis, preferred for all moderate to
high risk NSTE-ACS even if preloaded with clopidogrel
• Prasugrel - only before PCI, esp diabetics, STEMI –
remember contraindications

41. ……….Take Home
• Ticagrelor beneficial if given prehospital in STEMI
• In elective CABG, continue low dose aspirin and stop
clopidogrel, ticagrelor 5 days before and prasugrel 7
days before Sx
• In urgent surgery, continue continue low dose aspirin
and stop clopidogrel, ticagrelor, prasugrel 1 day
before . Weigh bleeding v/s thrombosis risk.
• Post CABG, continue aspirin lifelong, clopidogrel for
at least a month, esp for off pump surgery in pts with
low bleeding risk