DAPT after PCI-How long?

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Coronary stenting backgroundCoronary 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 PADCoronary 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 diseaseStone GW & Kirtane AJ. Chapter 13: Bare metal and drug-eluting coronary stents. In: Textbook of Interventional Cardiology 2012 (6th Edition)

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Coronary stenting benefits and risks BenefitsNumerous studies across a range of patient and lesion subsets have demonstrated an advantage of coronary stenting compared with conventional balloon angioplasty alone1Compared with CABG, coronary stenting is minimally invasive, carries lower risk of complications, and associated with shorter recovery time2

RisksStenting carries all of the same risks as angioplasty alone, including restenosis, and bleeding or infection at the site of catheter insertion2Stent 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 ACSStone GW & Kirtane AJ. Chapter 13: Bare metal and drug-eluting coronary stents. In: Textbook of Interventional Cardiology 2012 (6th Edition)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

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Vascular inflammation & repair with DESAlthough 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

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Why DAPT??

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.

Guidelines ACC/AHA (2011)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)Patients receiving DES for a nonACS indication:Clopidogrel 75mg daily should be given for at least 12 months not at high risk of bleeding (Class I, Level of Evidence: B)*

DOES ONE SIZE FIT ALL? *

Overview of clinical trials investigating DAPT duration in patients with CAD OPTIMIZE (NCT01113372)

DAPT (NCT00977938)

GLOBAL LEADERS (NCT01813435)Completion Q2 2016SECURITY (NCT00944333)TALOS-AMI (NCT02018055)CompletionQ4 2016SENIOR (NCT02099617)Completion Q2 2017DAPT-STEMI (NCT01459627)Completion Q4 2017*Primary endpoint reported in 2013 (Feres F et al. JAMA 2013;310:25102522)ISAR-SAFE (NCT00661206)PEGASUS TIMI 54 (NCT00526474)

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Results 12 Vs 3-6 months: no difference in death, major Hge, MI or stent thrombosis18-48 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/yearEvidence of increased overall mortality with prolonged DAPT (although weak)

Conclusion of ERC Systemic Review ReportWith newer generation DES

May be treated with 3-6 months of DAPTExtension beyond 12 months entails a tradeoffInability to predict life threatening bleeding limits appeal of 18-48 months DAPT over 6-12 months

DAPT Trial Prolonged DAPT group (per 1000 pts/year)

20 fewer MI09 more major bleeds05 more overall mortality

Current perspectives

*Clinical and Procedural Factors Associated With Increased Ischemic Risk or Increased Bleeding Risk2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapyin Patients With Coronary Artery DiseaseGlenn N. Levine,

*Factors used to calculate a DAPT score2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapyin Patients With Coronary Artery DiseaseGlenn N. Levine,A score of 2 is associated with a favorable benefit/risk ratio for prolonged DAPT while a score of

Confidential For Internal Use Only AstraZeneca 2014

Confidential For Internal Use Only AstraZeneca 2014

Confidential For Internal Use Only AstraZeneca 2014

Confidential For Internal Use Only AstraZeneca 2014

Confidential For Internal Use Only AstraZeneca 2014

Confidential For Internal Use Only AstraZeneca 2014

*2016 ACC/AHA Guideline- Recommendation of duration of DAPT in patients with SIHD treated with PCI2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapyin Patients With Coronary Artery DiseaseGlenn N. Levine,

2016 ACC/AHA Guideline- Recommendation of duration of DAPT in patients with SIHD treated with PCI2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapyin Patients With Coronary Artery DiseaseGlenn N. Levine,

2016 ACC/AHA Guideline- Recommendation for duration of DAPT in patients with ACS treated with PCI2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapyin Patients With Coronary Artery DiseaseGlenn N. Levine,

Various possibilities of duration of DAPT

Take home messageStent type and patient condition are important considerations in deciding optimal duration of DAPTWhile 1 month DAPT maybe sufficient for BMS, extended DAPT recommended for DES owing to delayed endothelializationAll 3 P2Y12 antagonists have shown efficacy and safety profile for 1 year in respective trialsIn low risk patients, shorter duration of DAPT has been shown non-inferior to longerStudies show benefit of extended DAPT beyond 1 year with high risk MI patients only

*Balancing Safety and RiskThere is a price to pay for greater platelet inhibition and the accompanying reduction in ischemic events

THANK YOU

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