1. Residual Platelet Reactivity,
Bleedings, and Adherence to
Treatment in Patients Having
Coronary Stent Implantation
Treated With Prasugrel
Nagi Abdalla

2. Contents
• Introduction and Aims
• Methods
• Results
• Discussion and Conclusion
• Limitations
• Summary

3. INTRODUCTION AND AIMS

4. Prasugrel
• Category: Antiplatelet Agent, thienopyridine class of
ADP receptor inhibitors
• Target patients: acute coronary syndromes planned for
percutaneous coronary intervention (PCI)

5. • Mechanism of Action:
– a pro-drug that is metabolized to both active (R-138727) and inactive
metabolites.
– The active metabolite irreversibly blocks the P2Y12 component of ADP
receptors on the platelet, which prevents activation of the GPIIb/IIIa
receptor complex, thereby reducing platelet activation and aggregation.
– Platelet aggregation returns to baseline within 5-9 days of discontinuation.
• Metabolism:
– Rapid intestinal and serum metabolism via esterase-mediated hydrolysis
(Cholinesterase) to a thiolactone (inactive),
– which is then converted, via CYP450-mediated (primarily CYP3A4 and CYP2B6)
oxidation, to an active metabolite

6. Aim of study
• Evaluation of bleeding rates and adherence to
treatment in patients treated with Prasugrel

7. METHODS

8. • Patients diagnosed with ACS where enrolled in
this study
• Indications to treatment with Prasugrel were:
– STEMI
– drug-eluting stent implantation in diabetics
– Stent thrombosis
– Left main CA drug-eluting stent implantation
– PCI in pts with high residual platelet reactivity on
Colpidogrel therapy

9. • Contraindications to prasugrel therapy were:
– Recent bleeding event or major surgery
– Previous TIA or stroke
• LD was: 60mg
• MD was:
– Elders  5mg/day
– Others10mg/day
• Dual antiplatelet therapy was recommended for
12 months.

10. • platelet reactivity assessment by light
transmittance aggregometry (APACT4, Helena
Laboratories, Milan, Italy) 7 to 30 days after the
index stenting procedure using adenosine
diphosphate (ADP) 10 mol as an agonist
• Blood samples anticoagulated with sodium
citrate 0.109 mmol (ratio 9:1) were obtained 7
days after loading with prasugrel 60mg
• Platelet-rich plasma, obtained by centrifuging
whole blood for 10 minutes at 200g 
stimulated with ADP 10 mol.

11. • Platelet aggregation (according to the Born
method) was evaluated considering maximal
percent platelet aggregation in response to
the stimulus
• COV of ADP platelet aggregation was 6.8%
• High residual platelet reacativity by ADP was
as platelet aggregation ≥70%

12. • Primary end point  study of any bleeding
event (major, minor, or minimal) according to
TIMI criteria
•TIMI major bleeding involves a hemoglobin drop >5 g/dL (with or without
an identified site) or intracranial hemorrhage or cardiac tamponade.
•TIMI minor bleeding involves a hemoglobin drop >3 g/dL but ≤5 g/dL, with
bleeding from a known site or spontaneous gross hematuria, hemoptysis, or
hematemesis.
•TIMI minimal bleeding involves a hemoglobin drop >4 g/dL but ≤5 g/dL
without an identified bleeding site.
• Secondary end point  study of all-cause
death, MI, stent thrombosis and stroke
• Questionnaires were done to assess the
clinical status of the patients

13. STATS
• Data were expressed as mean ± SD
• Chi-square test was used for comparison of
variables
• 2-tailed students test was used to test the
differences among continuous variables.
• Multivariable analyses to assess the contribution
of different factors to bleeding events
• Analyses were performed using SPSS 19

14. RESULTS

16. • Patients who bled during
follow-up showed a lower
residual platelet reactivity
compared to patients who
did not bleed

17. DISCUSSION & CONCLUSION

18. Findings of this study
1. In clinical practice major and minor bleeding event
rates associated with prasugrel therapy were
comparable to those reported in controlled
randomized trials.
2. The minimal bleeding event rate was higher than
reported but did not seem to affect adherence to
treatment.
3. Low residual platelet reactivity is the strongest
predictor of bleeding events in patients treated with
prasugrel.
4. High residual platelet reactivity is an uncommon (but
possible) occurrence during prasugrel therapy.
5. inter-individual variability may be an issue in
prasugrel in bleeding events in high responders (as in
clopedogrel)

19. Limitations of this study
1. Limited population in this study makes it
difficult to evaluate prasugrel associated
multicancer events reported in other studies
2. Patient follow up was 6 months but other
studies recommended more than 6 months
follow up for patients treated by dual therapy

20. Summary
• the main aim of this study was to report the
incidence of bleeding events and its impact on
adherence to treatment in real-world patients with
coronary artery disease treated with prasugrel.
• Other keys of interest about prasugrel in this study
includes:
– Inter-individual variability and prasugrel
– Prasugrel’s association with cancer and metastasis

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