- Polyvascular disease, where a patient has atherosclerosis in more than one vascular bed (e.g. coronary, carotid, and peripheral arteries) is common, with around 25-60% of patients with disease in one bed also having it in others. - Patients with polyvascular disease have higher rates of cardiovascular events than those with single-bed disease. - Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor such as clopidogrel or ticagrelor is frequently used long-term or lifelong in patients with polyvascular disease to reduce the risk of future cardiovascular events.

2. ACS and
Beyond

3. The Unique
Antiplatelet for Poly-
vascular Disease

4. Mahmoud Yossof
Head of Cardiology Department
Mansoura University, Egypt

5. WHY…?

6. Every two seconds,
one person dies
from cardiovascular
disease
World Health Organisation, Fact Sheet 317: Cardiovascular Diseases February 2007

7. Ischemic Heart Disease and Stroke Represent
the First 2 Common Causes of Death in Egypt
0 5 10 15 20 25
Diabetes
Hepatitis
Road injuries
CKD
LRI
COPD
Cirrhosis
Cancer
Stroke
IHD
IHD: Ischemic heart disease; COPD: chronic obstructive lung disease, LRI: lower respiratory infections,
CKD: chronic kidney disease.
%
%
%
%
%
Source: GBD Compare (http://v iz.healthmetricsandev aluati on.or g/ g
bd-compare/), 2010 available at: http://www.cdc.gov/globalhealth/countries/egypt/pdf/egypt_factsheet.pdf. Accessed on May 24, 2016

8. Atherosclerosis a systemic disease with manifestations in
multiple vascular beds
Circ Res. 2016;118:535-546

9. IHD, Ischemic Stroke, and PAD are the major clinical
manifestations of atherosclerosis
Circ Res. 2016;118:535-546
Ischemic
Stroke,Or
CAD
Ischemic
Heart
Disease
(IHD)
Peripheral
Arterial
Diseases
(PAD)

11. REACH Registry
REACH: The Reduction of Atherothrombosis for Continued Health
International, prospective cohort, 2003-2004
68, 236 patients
with either established atherosclerotic arterial disease
(CAD, PAD, CVD; n=55 814) or at least 3 risk factors for atherothrombosis (n=12 422),
enrolled from 5587 physician practices, in 44 countries
JAMA. 2007;297:1197-1206

12. :
Patients aged
≥45 years
At least
of four
criteria
1
1. Documented
cerebrovascular disease
Ischemic stroke or TIA
2. Documented
coronary disease
Angina, MI, angioplasty/
stent/bypass
3. Documented historical
or current intermittent
claudication associated
with ABI <0.9
4. At least
atherothrombotic
risk factors
3
1. Male aged 65 years
or female aged 70 years
2. Current smoking
>15 cigarettes/day
3. Type 1 or 2
diabetes
4. Hypercholesterolemia
5. Diabetic nephropathy
6. Hypertension
7. ABI <0.9 in either
leg at rest
8. Asymptomatic carotid
stenosis 70%
9. Presence of at least
one carotid plaque
REACH Registry inclusion criteria
Am Heart J 2006;151(4):786.e1-10.
| 13

13. ~25% of patients with CAD have athero-thrombotic disease
in other arterial territories
CAD
PAD
8.4%
1.6% CVD
44.6%
Patients with CAD =
59.3% of the
REACH Registry
population
CAD=coronary artery disease
PAD=peripheral arterial disease
CVD=cerebrovascular disease
4.7%
Multiple risk factors
only population
1. Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-
189.
(%s are of total population)

14. ~ 40% of patients with cerebrovascular disease have
athero-thrombotic disease in other arterial territories
8.4%
1.6%
1.2%
16.6%
Patients with CVD =
27.8% of the REACH
Registry population
(%s are of total population)
CAD
PAD
CVD
CAD=coronary artery disease
PAD=peripheral arterial disease
CVD=cerebrovascular disease
1. Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-
189.
Multiple risk factors
only population

15. CAD
PAD
CVD
~ 60% of patients with PAD have
athero-thrombotic disease in other arterial territories
1.2%
4.7%
1.6%
4.7%
Patients with PAD =
12.2% of the total
REACH Registry
population
(%s are of total population)
CAD=coronary artery disease
PAD=peripheral arterial disease
CVD=cerebrovascular disease
1. Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-
189.
Multiple risk factors
only population

16. Major CV event rates were doubled in patients with
poly-vascular disease compared with patients with a single
symptomatic arterial bed
One-Year CV Event Rates as a Function of Number of Symptomatic Disease Locations
JAMA. 2007;297:1197-1206

17. The incidences of CV death, MI, or stroke or of hospitalization for
athero-thrombotic event(s) for CAD, CVD, and PAD patients with
established disease
Breakdown of event rates
PAD
CAD
CVD



21.1% 1 in ~5
15.2% 1 in ~6
14.5% 1 in ~7
Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.

18. • The high event rates observed in this large, stable,
contemporary outpatient cohort of patients with established
atherosclerotic arterial disease or with multiple
atherothrombotic risk factors indicate that continued efforts
are needed to improve secondary prevention and
clinical outcomes.
REACH Registry
Conclusion
JAMA. 2007;297:1197-1206

19. What do studies in patients with
atherothrombosis show about
polyvascular disease?

20. 34.8%
10.8%
2.0%
0
10
20
30
40
50
1 Other 2 Other 3 Other
DETECT: Nearly 50% of Ischemic Stroke Patients Had
at Least One Other Form of Vascular Disease
* CAD, aortic atheroma, or PAD, as defined by history and assessment of other vascular beds.
Leys D et al. Cerebrovasc Dis. 2006;21:60-66..
▪ In the DETECT (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data
for Commitment of Treatment) survey, 753 patients admitted for IS were assessed for
evidence of disease in other vascular beds*
▪ 358 of 753 (47.5%) had at least one other manifestation of atherothrombosis
Number of vascular beds involved
Patients
(%)

21. SCALA: The Prevalence of PAD in IS Patients
ABI=Ankle-Brachial Index.
TIA is not a labeled indication in some countries.
Weimar C et al. J Neurol. 2007 Aug 3; [Epub ahead of print].
A study of 852 patients
with TIA or ischemic stroke
found 54.8% patients had a
form of PAD. This
included:
▪ 50.8% of the total
population had an ABI
≤0.9
▪ 10.0% of the total
population had
intermittent
claudication
54.8%
45.2%

22. PAD
CVD,CAD

23. Case Scenario
• 64 year-old gentleman who recently developed right sided weakness and
dysarthria for few minutes that resolved completely with no residual
defects. MSCT revealed 90% stenosis of the left internal carotid artery
that was treated with stenting.
a) Is DAPT required for him? If yes which P2Y12 inhibitor and for how long?
• Two years later he started to feel typical anginal chest pain on moderate
effort that wasn’t controlled by OMT. Stress tc99m showed large
reversible defect in the territory of the LAD that was fixed by coronary
stenting
b) Is DAPT required for him? If yes which P2Y12 inhibitor and for how long?

24. Case Scenario
• 54 year-old gentleman presented to the ER of a non-PPCI capable
hospital with inferior STEMI that was treated with thrombolytic
therapy as the the transfer time to a PPCI capable hospital would
exceed that recommended by the guidelines, after that and
within 24 hour he was transferred to a hospital where he was
treated with a stent.
a) Is DAPT required for him? If yes which P2Y12 inhibitor and for how long?
• 66 year-old hypertensive lady presented to the ER with anterior STEMI that
was treated with primary PCI. She has a history of paroxysmal AF for which
she was kept on OAC.
b) Is DAPT required for her? If yes which P2Y12 inhibitor and for how long?

25. Aboyans V,Et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for
Vascular Surgery (ESVS. Eur Heart J. 2017 Aug 26. doi: 10.1093/eurheartj/ehx095.

26. LEAD: Lower Extremity artery disease
Aboyans V,Et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for
Vascular Surgery (ESVS. Eur Heart J. 2017 Aug 26. doi: 10.1093/eurheartj/ehx095.

27. Aboyans V,Et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for
Vascular Surgery (ESVS. Eur Heart J. 2017 Aug 26. doi: 10.1093/eurheartj/ehx095.

28. Aboyans V,Et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS. Eur Heart J. 2017 Aug
26. doi: 10.1093/eurheartj/ehx095.
Management of CAS
CAS: Carotid artery stenosis
Clopidogrel
Or
Asprin

29. Aboyans V,Et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for
Vascular Surgery (ESVS. Eur Heart J. 2017 Aug 26. doi: 10.1093/eurheartj/ehx095.

30. Aboyans V,Et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for
Vascular Surgery (ESVS. Eur Heart J. 2017 Aug 26. doi: 10.1093/eurheartj/ehx095.

31. Recommendation for stable CAD
Marco Valgimigli, Et al:2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with
EACTS, European Heart Journal (2017) 0, 1–48

32. Updates in PAD
Jones WS, Baumgartner I, Hiatt WR, et al:
Ticagrelor Compared With Clopidogrel in Patients with Prior Lower Extremity
Revascularization for Peripheral Artery Disease.Circulation. 2016 Nov 13. pii:
CIRCULATIONAHA.116.025880.

33. 2011 AHA/ASA
Guidelines for the Prevention of Stroke in Patients
With Stroke or Transient Ischemic Attack
Stroke. 2011; 42: 227-276
AHA: American heart association; ASA: American Stroke Association

34. Newer P2Y12 inhibitors in patients with prior stroke or TIA
1. Eur Heart J. 2016 Jan 14;37(3):267-315
2. BMJ 2016;353:i2654
1
May 2016
2

35. When other P2Y12
were not tolerated

36. The TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome)
randomized study
Better Prognosis with switched DAPT
• The objective of the topic study was to
evaluate the benefit of switching dual
antiplatelet therapy (DAPT) from aspirin
plus a newer P2Y12 blocker to aspirin
plus clopidogrel 1 month after ACS
1-Thomas Cuisset,et al: Benefit of switching dual antiplatelet therapy after acute coronary syndrome, European Heart Journal (2017).

37. TROPICAL-ACS was aiming to investigate
the safety and efficacy of early de-
escalation of antiplatelet treatment from
prasugrel to clopidogrel guided by platelet
function testing (PFT).
Guided de-escalation of antiplatelet treatment was non-inferior
to standard treatment with prasugrel at 1 year after PCI in
terms of net clinical benefit.
primary endpoint (net clinical benefit)
Guided de-escalation of antiplatelet treatment in patients with acute
coronary syndrome undergoing percutaneous coronary intervention
(TROPICAL-ACS): a randomized,open-label, multicenter trial
Dirk Sibbing, et al, Guided de-escalation of antiplatelet treatment in patient swith acute coronary syndrome undergoing percutaneous coronary interventionl, the Lancet, 10.1016/S0140-6736(17)32155-4

38. Switching between oral P2Y12 inhibitors in the acute and chronic coronary
syndromes
European Heart Journal (2017) 0, 1–48 ESC GUIDELINESdoi:10.1093/eurheartj/ehx419

39. What if our
patient has
High-Bleeding
risk?

40. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa575/5898842
Assessment of Bleeding Risk

41. www.escardio.org/guidelines
2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without
persistent ST-segment elevation (European Heart Journal 2020 - doi/10.1093/eurheartj/ehaa575)
©ESC
Figure 5
Determinants of
antithrombotic
treatment in
coronary artery
disease.
Intrinsic (in blue: patient’s
characteristics, clinical presentation
& comorbidities) and extrinsic (in
yellow: co-medication & procedural
aspects) variables influencing the
choice, dosing, and duration of
antithrombotic treatment.
Balance between ischemic and bleeding risk

42. Strategies to reduce bleeding risk related to PCI
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa575/5898842

43. Risk scores validated for dual antiplatelet therapy
duration decision-making
Marco Valgimigli, Et al:2017 ESC focused update on dual antiplatelet therapy in
coronary artery disease developed in collaboration with EACTS, European Heart Journal (2017) 0, 1–48

44. What if our
patient has
AF?

45. Algorithm for antithrombotic therapy in NSTEMI ACS
patients with AF undergoing PCI or medical management
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa575/5898842

46. Case Scenario
• 64 year-old gentleman who recently developed right sided weakness and
dysarthria for few minutes that resolved completely with no residual
defects. MSCT revealed 90% stenosis of the left internal carotid artery
that was treated with stenting.
a) Is DAPT required for him? If yes which P2Y12 inhibitor and for how long?
• Two years later he started to feel typical anginal chest pain on moderate
effort that wasn’t controlled by OMT. Stress tc99m showed large
reversible defect in the territory of the LAD that was fixed by coronary
stenting
b) Is DAPT required for him? If yes which P2Y12 inhibitor and for how long?

47. Case Scenario
• 54 year-old gentleman presented to the ER of a non-PPCI capable
hospital with inferior STEMI that was treated with thrombolytic
therapy as the the transfer time to a PCI capable hospital would
exceed that recommended by the guidelines, after that and
within 24 hour he was transferred to a hospital where he was
treated with a stent.
a) Is DAPT required for him? If yes which P2Y12 inhibitor and for how long?
• 66 year-old hypertensive lady presented to the ER with anterior STEMI that
was treated with primary PCI. She has a history of paroxysmal AF for which
she was kept on OAC.
b) Is DAPT required for her? If yes which P2Y12 inhibitor and for how long?

48. Management of ACS patient received
fibrinolytic therapy
ACS patients with elective PCI
Management of ACS patients on oral
anticoagulants
Management of ACS patients with history of Lower
extremity artery disease
Switching between oral P2Y12 inhibitors in
the acute and chronic coronary syndromes
proven efficacy and safety in
elderly
Clopidogrel in real world evidence data
Management of patients with CCS and
AF
≥200 Million patients treated with plavix
5
Management ACS patient with high risk
of bleeding
Management of patients with CCS and sinus rhythm
Management of ACS Patients with history of TIA/ Stroke
I should use
clopidogrel
Reasons

49. Take Home Message
1. Clopidogrel
• Clopidpgrel is P2Y12 inhibitor of choice in patients received lytic therapy
• Clopidpgrel is P2Y12 inhibitor of choice in patients with LEAD1
• Clopidpgrel is P2Y12 inhibitor of choice in patients with CAS1
• Clopidpgrel is P2Y12 inhibitor of choice in patients with stable CAD undergoing PCI
• Patients on oral anticoagulants or Patients with high risk of bleeding
• Clopidpgrel is P2Y12 inhibitor of choice in patients received triple therapy
• Clopidpgrel Has convenient once daily dosing, No specific dose in CKD pt. and Is
generally well tolerated
LEAD: Low extremity arterial disease CAS : Carotid artery stenting CAD : Coronary artery Disease
1,2:Aboyans V,Et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS. Eur Heart J. 2017 Aug 26. doi: 10.1093/eurheartj/ehx095.
2:Marco Valgimigli, Et al:2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS, European Heart Journal (2017) 0, 1–48

50. S
Thank You