General Overview and Highlights of the North American Consensus Document on Anticoagulation in the Atrial Fibrillation Patients with ACS or PCI Dominick J. Angiolillo, MD, PhD Professor of Medicine Medical Director - Cardiovascular Research Program Director – Interventional Cardiology Fellowship University of Florida College of Medicine - Jacksonville

Presenter Disclosure Information Name: Dominick J Angiolillo Within the past 12 months, the presenter or their spouse/partner have had a financial interest/arrangement or affiliation with the organization listed below. Received payment as an individual for: a) Consulting fee or honorarium from Amgen, Bayer, Chiesi, Sanofi, Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Merck, Abbott Vascular, Pfizer, and PLx Pharma; b) Honorarium for participation in review activities (DSMB member) from CeloNova, Johnson & Johnson, St. Jude, and Sunovion. c) Honorarium from the American Board of Internal Medicine (Interventional Cardiology Subspecialty Exam Writing Committee Member) Institutional payments for: a) Grant support industry: from Amgen, Glaxo-Smith-Kline, Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Janssen Pharmaceuticals, Inc., Osprey Medical, Inc., Novartis, CSL Behring, and Gilead. b) Grant in gift: Spartan; Scott R. MacKenzie Foundation c) Federal agency: NIH

AF + PCI: Dimension of the Problem AF is the most common cardiac arrhythmia occurring in 1- 2% of the general population, with a prevalence that increases with age. Among AF patients at moderate-to-high risk for cardioembolic events, the use of chronic OAC is the mainstay of stroke prevention. The prevalence of CAD also increases with age and coexists in 20- 30% of AF patients; ~ 5–7% of PCI patients, who are routinely treated with DAPT, also have AF or other indications for OAC. These estimates are expected to increase as the global burden of AF increases, driven in large part to the aging population. These observations raise an important clinical problem regarding the optimal antithrombotic management of patients undergoing PCI who also have AF. Currently, there are limited evidenced-based data on the optimal antithrombotic treatment regimen of PCI patients who also require OAC due to AF, and Guidelines provide limited insights on the management of these high-risk patients.

The 2011 North American Perspective Faxon DP et al. Circ Cardiovasc Interv. 2011;4:522-534

AF + PCI: A North American Perspective – 2016 Update Dominick J. Angiolillo, MD, PhD; Shaun G. Goodman, MD; Deepak L. Bhatt, MD, MPH; John W. Eikelboom, MD; Matthew J. Price, MD; David J. Moliterno, MD; Christopher P. Cannon, MD; Jean-Francois Tanguay, MD; Christopher B. Granger, MD; Laura Mauri, MD; David R. Holmes, MD; C. Michael Gibson, MD; David P. Faxon, MD

AF + PCI: A North American Perspective – 2016 Update The Challenge: Discerning the choice of antithrombotic therapy Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Consensus Document Objectives Provide current views on: embolic/stroke risk ischemic/thrombotic cardiac risk bleeding risk Describe the recent advances in antithrombotic (antiplatelets and anticoagulants) pharmacology, stent designs, and clinical trials relevant to the field. Provide expert consensus derived recommendations, using a pragmatic approach, on the management of patients with AF undergoing PCI. Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Defining the need for chronic OAC CHA2DS2-VASc Score CHF/LV dysfunction (LVEF ≤40%) 1 Stroke/TIA/TE 2 Hypertension 1 Vascular disease (prior MI, PAD, or aortic) 1 Age ≥75 years 2 Age 65–74 years 1 Diabetes mellitus 1 Sex category (ie, female sex) 1 Low risk (no antithrombotic therapy) defined as CHA2DS2-VASc of 0 in males (“age <65 and lone AF”) CHA2DS2-VASc of 1 in females (“age <65 and lone AF”) Lip GY, et al. Chest. 2010;137:263–272

The North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI

AF + PCI: A North American Perspective – 2016 Update Pre-procedural Considerations 1. Define “Appropriateness” for PCI. - Consider Appropriateness Criteria for PCI - Nothing wrong with trying medical therapy first - Once stent is implanted: point of no return! A U I Patel M et al JACC 2009

AF + PCI: A North American Perspective – 2016 Update Pre-procedural Considerations 2. Ischemic/thrombotic & bleeding risk stratification Levine G et al. Circulation 2016

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI

The North American Perspective – 2016 Update Procedural Considerations 1. Vascular Access: Radial Consistently shown to be associated with less bleeding Mortality benefit 2. Stent choice: New generation DES - New generation DES: better safety even compared with BMS; typically AF patients also have more complex CAD - BMS: if considered, should only be for simple lesions (short length/ large diameter) - BVS: high early ST rates which increase with lesion complexity (some advocate more potent antithrombotic therapy) - Other new stent platforms (e.g., DCS): not available in the US

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI Whenever possible (i.e., elective / non-emergent procedures), a brief period of wash- out from the anticoagulant effect of OAC is preferable. For patients on a VKA: INR to be preferably ≤2.0 when using a radial approach (recommended) and ≤ 1.5 if femoral approach is used. Patients on a NOAC: withhold therapy for 24 hours (or 48 hours for patients with impaired renal function with dabigatran) irrespective of vascular access site. Although patients with stable CAD can forgo bridging with parenteral anticoagulation, this should be considered for patients presenting with an ACS.

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI Given the current controversies over the net benefits of bivalirudin over other antithrombotic treatment regimens as well as differences in practice patterns among interventionalists, this expert consensus does not recommend a specific parenteral antithrombin agent over another. However, bivalirudin appears to be a reasonable treatment option in patients at higher risk of bleeding, particularly in those presenting with ACS and if a femoral approach is being used.

AF + PCI: A North American Perspective – 2016 Update The choice of OAC (VKA or NOAC) is at the discretion of the treating physician, with patients informed on the risk-benefit profiles of each agent based on available data. Continuing with the same OAC after PCI may be reasonable, particularly if the patient has been compliant and has not experienced complications. If a VKA is chosen, maintain an INR in the 2.0-3.0 range (ideally between 2.0–2.5). A NOAC at lowest therapeutic dose effective for stroke prevention should be preferred over a VKA in patients unable to have their INR routinely monitored or are unable to maintain INR in the therapeutic range. A recommendation on use of doses lower than the full anticoagulant dose of a specific NOAC cannot be provided until further data become available.

The North American Perspective – 2016 Update This expert consensus recommends that the duration of DAPT in AF patients treated with stents also on OAC should not extend to a full 12 months and to consider SAPT starting within the first 6-months (0 to 6 months post-stenting depending on the ischemic/thrombotic and bleeding risk profile) for up to 12 months. This group consensus recommends that dropping aspirin rather than a P2Y12 receptor inhibitor should be considered (favoring the use of clopidogrel and avoiding prasugrel or ticagrelor).

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI Discontinuation of one antiplatelet agent should be considered 1-3 months after PCI, this may occur sooner (including immediately after PCI) or later (but not beyond 6 months) according to the ischemic/thrombotic and bleeding risk profiles of the patient. Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Aspirin might be no longer needed after 12 months in AF patients with stable CAD on VKA Age ad gender adj. HR (95% CI) No difference In CV death/MI/CVA in patients treated with VKA + APT versus patients treated with VKA alone adj. HR: 1.15 95% CI 0.58-2.27 p=0.697 SAT Reference DAPT 1.58 [0.72-3.47] VKA+SAT 7.30 [3.91-13.64] VKA alone 1.69 [0.39-7.30] 0.1 1 100 CORONOR – 4,184 patients on oral anticoagulation with stable (>12 mo) CAD Hamon M, et al. J Am Coll Cardiol 2014;64:1430–6

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI Balanced thrombotic / bleeding risk Shorter (e.g., 1 month) and longer (e.g., 3 months) DAPT duration should be considered in patients treated with BMS and DES, respectively. Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI High bleeding / low thrombotic risk Discontinuation of one antiplatelet agent may be considered immediately after PCI if patients at very-high bleeding risk Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI High thrombotic / low bleeding risk Shorter (e.g., 3 month) and longer (e.g., 6 months) DAPT duration should be considered in patients treated with BMS and DES, respectively. Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Pragmatic algorithm for the management of AF patients requiring OAC undergoing PCI More frequent follow-up visits. Don’t leave in the exclusive care of PCP. Choice/duration of antithrombotic therapy may change over time depending on clinical evolution. At 1-year post-PCI need to evaluate need to continue with any antiplatelet agent based on bleeding/thrombotic risk.

AF + PCI: A North American Perspective – 2016 Update Peri- and post-procedural Considerations Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Ongoing trials of NOACs in AF patients undergoing PCI AHA 2016 NOAC wins ESC 2017 ? Angiolillo DJ et al. Circ Cardiovasc Interv. 2016

AF + PCI: A North American Perspective – 2016 Update Stay tuned for 2017 Update Dominick J. Angiolillo, MD, PhD; Shaun G. Goodman, MD; Deepak L. Bhatt, MD, MPH; John W. Eikelboom, MD; Matthew J. Price, MD; David J. Moliterno, MD; Christopher P. Cannon, MD; Jean-Francois Tanguay, MD; Christopher B. Granger, MD; Laura Mauri, MD; David R. Holmes, MD; C. Michael Gibson, MD; David P. Faxon, MD