Includes all major landmark trials of anti-platelets

1. Dr. Vijay Yadav
DM Resident
MCVTC, IOM
TRIALS ON ORAL ANTI-
PLATELET AGENTS

4. ISIS-2 was the largest trial of ASPIRIN in patients with STEMI.
It provided the single strongest piece of evidence that aspirin reduces
mortality.
There was no increase in the risk of major bleeding or hemorrhagic
stroke in patients receiving aspirin
AGENTS 5 WEEKS
MORTALITY
REDUCTION
ASPIRIN 23%
STREPTOKINASE 25%
BOTH 42%

6. CLOPIDOGREL PRASUGREL TICAGRELOR CANGRELOR
CLASS P2Y12,
Thienopyridine
P2Y12,
Thienopyridine
P2Y12,
Triazolopyrimidi
ne
ATP analogue
Reversibility Irreversible Irreversible Reversible Reversible
Activation Prodrug Prodrug Active drug Active drug
Onset 2-8 hours 30 min-4hrs 30 min-4hrs 2 minutes
Offset 7-10 days 7-10 days 3-5 days 30-60 min
CYP CYP2C19 No CYP3A1 No
Withdrawl
bedore CABG
5 days 7 days 5 days No

8. ASA + Clopid ASA
Primary end point 9.3% 11.4%
Secondary end
point(refractory
ischemia)
16.5% 18.8%

10. CREDO TRIAL (2002)
ASA + CLOPID ASA
Primary end point
(CV death, MI,
Stroke)
8.5% 11.5%
Relative risk reduction
(RRR) at 1 year
26.9%

12. CLOPID PLACEBO
Primary
endpoint
15% 21.7%
Addition of Clopidogrel to Aspirin
in patients with STEMI receiving
fibrinolytic therapy improved the
patency rate of IRA & reduced
ischemic complications

13. No significant difference
in primary end point at
30 days.
In patients who
underwent PCI, double
dose clopidogrel was
a/w 15% RRR in primary
end point and 42%
relative reduction in
stent thrombosis.

14. The trial showed that after 28 months, addition of clopidogrel to aspirin was not
better than aspirin alone in reducing primary composite end point in patients with
multiple CV risk factors in the ABSENCE of ACS or PCI.

16. PRASUGREL TRIALS

20. • Bleeding
• Hb drop > 3g/dL
• Hct drop > 10%
• No obvious blood loss
• Hb drop > 4g/dL
• Hct drop > 12%
• ICH
• Hb drop > 5g/dL
• Hct drop > 15%
TIMI BLEEDING
MAJOR MINOR

22. • Aspirin treated patients (n=9326) with NSTE-ACS in whom a medical
management strategy was chosen were randomized to receive either
prasugrel (30/10 mg) or clopidogrel (300/75 mg). A prasugrel
maintainance dose was adjusted to 5 mg for patients with age ≥ 75
years or who weighted < 60 kg.
• Primary end points: CV death, MI, Stroke

23. At a median follow -up of 17 months , there were no differences between
prasugrel and clopidogrel in the primary end point.
The rates of severe and ICH were low and
similar between the two groups.
Prasugrel 5 mg was not associated with an
ischemic benefit in patients older than 75 years
as comapred to clopidogrel.

25. Administering 30mg prasugrel prior to CAG in NSTE-ACS
patients offers no benefit in delaying therapy until a lesion for
PCI is identified on CAG

26. TICAGRELOR
TRIALS

34. The primary end point was significantly
to a similar extent with either doses.
Major bleeding was increased with
Ticagrelor (90mg >> 60mg)
Ticagrelor was not associated with fatal
bleedings or ICH
Overall, the findings are supportive for the use of Ticagrelor
60mg BD for secondary prevention of long term ischemic events
among patients who experienced a prior MI

35. MOJITO (Mashed Or Just Integral pill of TicagrelOr)
study – Feb 2015 JACC
• Prospective, 4-center, international, randomized, active-controlled study with the aim
to evaluate the superiority of ticagrelor crushed pills versus integral tablets of equal
dose in decreasing platelet reactivity in P2Y12-naive, STsegment elevation myocardial
infarction (STEMI) patients undergoing primary percutaneous coronary intervention.
• Crushed tablets were prepared placing 2 ticagrelor pills in a mortar and mashing for 60
s using a pestle. A 50 ml of purified water was added, and the suspension was mixed up
before drinking.
• Platelet function testing was performed with VerifyNow at baseline and at 1, 2, 4, and 8
h.
• Results are reported in P2Y12 reaction units (PRU).
• High-platelet reactivity (HPR) was defined as a PRU >208. The primary endpoint was
PRU 1 h after LD.
• The study showed that crushed ticagrelor tablet administration in STEMI patients is
feasible and provides earlier platelet inhibition compared with standard integral tablets.

37. Cangrelor
Trials

40. VerifyNow
P2Y12
Vasodilator stimulated
phosphoprotein

41. 1) Addition of cangrelor leads to prompter and more potent
platelet inhibitory effects compared with crushed ticagrelor
alone, with significant differences observed as early as 5
minutes of bolus administration.
2) Cangrelor maintained lower levels of platelet reactivity
compared with crushed ticagrelor at 30 minutes and until 2
hours.
3) Cangrelor can be used in patients undergoing PPCI as a
strategy to achieve prompt and potent P2Y12 inhibitory
effects and bridge the gap in platelet inhibition associated
with the use of ticagrelor.

42. SIHD undergoing PCI

43. NSTEMI undergoing PCI

44. STEMI UNDERGOING
PCI

45. THANK YOU