Clopidogrel is a pro-drug that requires hepatic metabolism to become active. It is a cornerstone of treatment for acute coronary syndrome (ACS) as dual antiplatelet therapy with aspirin. The CURE trial showed clopidogrel plus aspirin reduces cardiovascular events in ACS patients compared to aspirin alone. Later trials like CREDO found clopidogrel reduces events in patients post-percutaneous coronary intervention compared to aspirin. Newer P2Y12 inhibitors like prasugrel and ticagrelor are more effective at preventing ischemia but with increased bleeding risk. De-escalating dual antiplatelet therapy from newer drugs to clopidogrel appears safe and effective.

1. The role of Clopidogrel
in
Atherosclerosis Vascular
Disease
Ahmed Taha Abdelwahed, MD, EHRA-Certified
Lecturer of Cardiology
Department of Cardiology, Faculty of Medicine,
Zagazig University, Egypt;
Heart Center, Department of Cardiology, Tampere University Hospital, and School of
Medicine, Tampere University- Finland

2. Arteriosclerotic Vascular Disease or ASVD
 Atherosclerosis : the condition in which an artery wall thickens as the result of a build-up of fatty materials
such as cholesterol affecting arterial blood vessels,
 A chronic inflammatory response in the walls of arteries, due to the accumulation of macrophage white
blood cells and promoted by Low-density lipoproteins without adequate removal of fats and cholesterol
from the macrophages by functional high-density lipoproteins.

5. ACS mechanism

6. Background
1. Antiplatelet therapy has remained the cornerstone of treatment for patients with
ACS :” Platelet adhesion, activation, and aggregation after plaque rupture or
erosion are the major determinants of arterial thrombosis leading to ACS”
2. Anti-platelet therapy is vital
3. Multiple platelet-signaling pathways are involved in thrombus formation and are
potential targets for therapies.
4. Dual antiplatelet therapy with a combination of aspirin and either P2Y12-receptor
inhibitors should be the treatment of choice in patients with ACS.

7. ADP receptors
G-protein coupled
receptors (GPCRs)
ion-channel linked
receptor

9. pharmacodynamics
thienopyridines

10. Metabolism of P2Y12 Receptor
Antagonists
Adapted from: Schomig A. NEJM. 2009;361(11):1108-1111.
Effient (Prasugrel) Product Monograph March 11, 2011 version.
Brilinta (Ticagrelor) Product Monograph May 26, 2011 version.
Plavix (Clopidogrel) Product Monograph May 9, 2011 version.

11. Clopidogrel
 is a pro-drug, with hepatic metabolism (2 hours) required to form the highly reactive and
short-lived compound responsible for its activity .
 The requirement for cytochrome P450 family of enzymes for metabolism (activation)

12. P2Y12 receptor inhibitors for use in non-ST-
segment elevation acute coronary syndrome

13. Evidence based data
Clinical trials

17. CURE study
The Clopidogrel in Unstable Angina to
Prevent Recurrent Events
Clinical trials

18. Cure study

19. Cure study

20. CREDO study
Clopidogrel for Reduction of Events During
Observation
Clinical trials

24. CAPRIE study
Clopidogrel versus aspirin in patients at
risk of ischemic events
Clinical trials

27. CHARISMA study
The Clopidogrel for High Atherothrombotic
Risk and Ischemic Stabilization,
Management, and Avoidance
Clinical trials

29. TALOS AMI study
TicAgrelor Versus CLOpidogrel in
Stabilized Patients With Acute Myocardial
Infarction
De-escalation of DAPT therapy
What’s new in 2021

30. Main endpoints

31. Subgroup analysis

32. De-escalation trials

33. De-escalation trials meta-analysis

34. Guidelines
From trials to guidelines

63. Conclusion
 Prasugrel and ticagrelor is more efficacious in preventing ischemic events in patients
with ACS undergoing PCI, but with increased bleeding complications.
 Dual antiplatelet treatment has only been efficacious in ACS and post-PCI patients.
 Newer thienopyridines did not show advantages over and above those of ticlopidine or
clopidogrel as to reduction of stroke.
 De-escalation of Dual Antiplatelet Therapy Appears Safe and Effective, either
from ticagrelor or prasugrel to Clopidogrel.
 genotype-guided DAPT de-escalation may be favored. Moreover, clopidogrel may be
considered the first choice of antiplatelet therapy in elderly patients with ACS.
 patients with stroke or very high-risk TIA, intensive DAPT with aspirin plus clopidogrel
should be administered for 21–28 days after the acute event, followed by less intensive
treatment for up to 90 days, to minimize the risk of bleeding complications; clopidogrel
is potentially more effective than aspirin as antiplatelet monotherapy.
 In patients with symptomatic PAD, or those who have undergone peripheral
revascularization, clopidogrel is the preferred agent