NOAC in patients with Atrial Fibrillation and Acute Coronary Syndromes

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1 NOAC in patients with Atrial Fibrillation and Acute Coronary Syndromes Matteo Bertini, MD, PhD Department of Cardiology, Arcispedale S. Anna University of Ferrara

2 Atrial fibrillation and PCI Among ACS patients undergoing PCI, approximately 5% to 21% of patients have concomitant AF. Rubboli et al., J Interv Cardiol 2009 Despite overlap in the occurence of these syndromes, the pharmacotherapies used to manage AF and ACS differ

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4 VKA + antiplatelets The management of AF patients who undergo stent placement for an ACS is challenging -Bleeding associated with antithrombotic therapy -AF-related ischaemic stroke -Stent thrombosis Haemorragic risk Thrombotic risk

5 Ischaemic stroke associated with warfarin, aspirin and clopidogrel in patients with AF n = Hansen et al. Arch Int Med 2010; 170:

6 Bleeding associated with warfarin, aspirin and clopidogrel in patients with AF n = Hansen et al. Arch Int Med 2010; 170:

7 TRIPLE THERAPY: clinical evidences WOEST Trial

8 Primary outcome: any bleeding episode within 1 year of PCI

9 600 pts ISAR-TRIPLE Indication to VKA+DES (ACS or elective) 9-month follow-up Composite endpoint : death, MI, stroke, ST, TIMIbleeding

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11 NOACS in association with DAPT (aspirin+clopidogrel)? In all NOACS trials ( RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) patients were excluded from enrollment if receiving new P2Y12 And conversely, AF patients requiring OAC were systematically excluded from recent ACS trials. Some data are available in non AF patients

12 97% patients were taking aspirin 81% patients were taking aspirin plus a P2Y12-receptor inhibitor (predominantly clopidogrel)

13 Primary Outcome CV Death, MI, Ischemic Stroke APPRAISE-2 Apixaban 279 (7.5%) Placebo 293 (7.9%) HR 0.95; 95% CI ; p=0.509

14 TIMI Major Bleeding APPRAISE-2 Apixaban 48 (1.3%) Placebo 18 (0.5%) HR 2.59; 95% CI ; p=0.001

15 N=15,526* ATLAS ACS 2 TIMI 51 Physician's decision to add thienopyridine or not Stratum 1: ASA alone (7%) ASA dose = mg/day Stratum 2: ASA + thienopyridine (93%) Placebo n=355 Rivaroxaban 2.5 mg bid n=349 Rivaroxaban 5 mg bid n=349 Placebo n=4821 Rivaroxaban 2.5 mg bid n=4825 Rivaroxaban 5 mg bid n=4827 Mega et al, 2011 Event-driven study 1002 events

16 Estimated cumulative rate (%) Primary efficacy endpoint (CV death/mi/stroke) Both rivaroxaban doses, both strata 12 2-year Kaplan Meier estimate 10 8 Placebo 10.7% 8.9% Rivaroxaban Number at risk Months after randomization Placebo Rivaroxaban 10, HR=0.84 ( ) ARR=1.7% mitt p=0.008 ITT p=0.002 NNT=56 Mega et al, 2011 ATLAS ACS 2 TIMI 51

17 Safety endpoint Non-CABG TIMI major bleed Rivaroxaban 2.5 mg bid (n=5115) Rivaroxaban 5 mg bid (n=5110) Placebo (n=5125) K M estimate at 2 years 1.8% 2.4% 0.6% p value versus placebo <0.001 <0.001 ICH K M estimate at 2 years 0.4% 0.7% 0.2% p value versus placebo Fatal bleeding K M estimate at 2 years 0.1% 0.4% 0.2% p value versus placebo Fatal ICH K M estimate at 2 years 0.1% 0.2% 0.1% p value versus placebo Mega et al, 2011 ATLAS ACS 2 TIMI 51

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19 AF + NOAC + DAPT

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21 However. 1. PIONEER AF-PCI is not powered to detect differences in stroke rates 2. it will still remain uncertain if rivaroxaban 2.5 mg b.i.d. would adequately reduce strokes in AF, even when combined with antiplatelet agents

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24 In practice what to do? 1. Personalize antithrombotic therapy according to: - Stroke risk (CHA 2 DS 2 VASC) - Bleeding risk (HAS BLED) - Clinical setting (ACS vs elective) - Stent type (DES vs BMS) - Time from PCI/ACS

25 2. Prefer: In practice what to do? - The lower tested dose for stroke prevention in AF (that is, dabigatran 110 mg b.i.d., rivaroxaban 15 mg o.d. or apixaban 2.5 mg b.i.d.) to minimize the risks of bleeding - Clopidogrel instead of the more potent ticagrelor and prasugrel - New generation DES (or BMS) over first generation DES - Use of the radial approach, thus minimizing the risk of access site bleeding

26 Thanks!

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28 Thanks!

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30 Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), uropean Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS)

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34 WOEST Trial limitations - Only 69% of patients received OAC due to AF - Most of the patients underwent elective PCI (70 75%) -The femoral approach was used in 74%, increasing access site bleeding - The differences between dual and triple therapy for the primary end-point of all bleeding were driven by minor bleeding events - Proton pump inhibitors (PPIs) were not used routinely - Triple therapy was continued for 12 months (and thus, the increased risk of bleeding is unsurprising) - The trial population size was too small to meaningfully assess major efficacy outcomes such as stent thrombosis or death