UPTODATE WITH MOST CURRENT GUIDELINES (ACC/AHA SEPT 2016)

1. DAPT after PCI-How
long?

2. Coronary stenting – background
• Coronary stenting: standard procedure during
PCI that provides mechanical scaffolding to maintain
vessel patency in treatment of IHD
– Similar stents/ procedures also used in non-coronary
vessels, eg, in legs in PAD
• Coronary stents developed to overcome two major
limitations of balloon angioplasty:1
– Abrupt closure (occurring acutely or within the first
several days after angioplasty)
– Restenosis (occurring later, within months after
procedure)
CHD, coronary heart disease;
PAD, peripheral artery disease
1. Stone GW & Kirtane AJ. Chapter 13: Bare metal and drug-eluting coronary stents.
In: Textbook of Interventional Cardiology 2012 (6th Edition)

3. Coronary stenting – benefits and risks
Benefits
• Numerous studies across a range of patient and lesion subsets have demonstrated an advantage
of coronary stenting compared with conventional balloon angioplasty alone1
• Compared with CABG, coronary stenting is minimally invasive, carries lower risk of complications,
and associated with shorter recovery time2
Risks
• Stenting carries all of the same risks as angioplasty alone, including restenosis, and bleeding or
infection at the site of catheter insertion2
• Stent thrombosis is an infrequent but serious complication following stent placement1
– The mechanisms underlying stent thrombosis are multifactorial and include stent-related
factors as well as patient and procedural factors; it occurs more frequently in complex patients
and lesions, especially in patients with ACS
1. Stone GW & Kirtane AJ. Chapter 13: Bare metal and drug-eluting coronary stents. In: Textbook of Interventional Cardiology 2012 (6th Edition)
2. The Society for Cardiovascular Angiography & Interventions (SCAI). Benefits and Risks of Angioplasty and Stenting (accessed May 2014)
CABG, coronary artery bypass graft;
MI, myocardial infarction

4. Vascular inflammation & repair with DES
• Although positive effects of DES reduce inflammation and restenosis, negative
effects delay re-endothelialization and impair endothelial function.
• Delayed re-endothelialization and impaired endothelial function are linked to stent
thrombosis and adverse clinical outcomes after DES use.
• Effects of DES on vascular inflammation and repair dictate requirements for
extended-duration dual antiplatelet therapy.
Vascular Inflammation and Repair : Implications for Re-Endothelialization, Restenosis, and Stent
Thrombosis. Teruo Inoue et al

5. Why DAPT??

6. Dual Antiplatelet Therapy
A number of studies in different clinical settings have shown that clopidogrel,
either alone or added to aspirin, is superior to aspirin Monotherapy in reducing
morbid and/or fatal endpoints.

7. Guidelines – ACC/AHA (2011)
1.Patients receiving stent (BMS or DES) during PCI for
ACS:
P2Y12 inhibitor therapy should be given for at least 12 months
(Class I, Level of Evidence: B)
1.Patients receiving DES for a non–ACS indication:
Clopidogrel 75mg daily should be given for at least 12 months not at
high risk of bleeding (Class I, Level of Evidence: B)
7

8. DOES
ONE
SIZE
FIT
ALL?
8

9. Overview of clinical trials investigating DAPT duration
in patients with CAD
OPTIMIZE
(NCT01113372)
DAPT
(NCT00977938)
GLOBAL LEADERS
(NCT01813435)
Completion Q2 2016
SECURITY
(NCT00944333)
TALOS-AMI
(NCT02018055)
Completion
Q4 2016
SENIOR
(NCT02099617)
Completion Q2 2017
DAPT-STEMI
(NCT01459627)
Completion
Q4 2017
*Primary endpoint reported in 2013 (Feres F et al. JAMA 2013;310:2510–2522)
ISAR-SAFE
(NCT00661206)
PEGASUS TIMI 54
(NCT00526474)

13. Results
•12 Vs 3-6 months: no difference in death, major Hge, MI or stent
thrombosis
•18-48 Vs 6-12 months:
– no difference in all cause death, reduced MI or stent thrombosis
but increased major Hge
– 03 fewer ST, 06 fewer MI but 05 more major Hge and 02 more
deaths per 1000 pts/year
– Evidence of increased overall mortality with prolonged DAPT
(although weak)

14. Conclusion of ERC Systemic Review Report
•With newer generation DES
– May be treated with 3-6 months of DAPT
– Extension beyond 12 months entails a tradeoff
– Inability to predict life threatening bleeding limits appeal of 18-48
months DAPT over 6-12 months

15. DAPT Trial
•Prolonged DAPT group (per 1000 pts/year)
–20 fewer MI
–09 more major bleeds
–05 more overall mortality

16. Current perspectives

19. 19
Clinical and Procedural Factors Associated With Increased
Ischemic Risk or Increased Bleeding Risk
2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy
in Patients With Coronary Artery Disease
Glenn N. Levine,

20. 20
Factors used to calculate a DAPT score
2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy
in Patients With Coronary Artery Disease
Glenn N. Levine,
A score of ≥2 is associated with a
favorable benefit/risk ratio for
prolonged DAPT while a score of <2 is
associated with an unfavorable
benefit/risk ratio

21. Confidential – For Internal Use Only • AstraZeneca 2014

22. Confidential – For Internal Use Only • AstraZeneca 2014

24. Confidential – For Internal Use Only • AstraZeneca 2014

26. 26
2016 ACC/AHA Guideline- Recommendation of duration of DAPT in
patients with SIHD treated with PCI
2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy
in Patients With Coronary Artery Disease
Glenn N. Levine,

27. 2016 ACC/AHA Guideline- Recommendation of duration of
DAPT in patients with SIHD treated with PCI
2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy
in Patients With Coronary Artery Disease
Glenn N. Levine,

28. 2016 ACC/AHA Guideline- Recommendation for
duration of DAPT in patients with ACS treated with PCI
2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy
in Patients With Coronary Artery Disease
Glenn N. Levine,

29. Various possibilities of duration of DAPT

30. Take home message
• Stent type and patient condition are important considerations in deciding
optimal duration of DAPT
• While 1 month DAPT maybe sufficient for BMS, extended DAPT
recommended for DES owing to delayed endothelialization
• All 3 P2Y12 antagonists have shown efficacy and safety profile for 1 year in
respective trials
• In low risk patients, shorter duration of DAPT has been shown non-inferior
to longer
• Studies show benefit of extended DAPT beyond 1 year with high risk MI
patients only

31. 31
Balancing Safety and Risk
There is a price to pay for greater platelet inhibition and the accompanying reduction
in ischemic events

32. THANK YOU