NOACS: Emerging data in ACS/IHD John McDonald Royal Blackburn Hospital GP Update meeting June 2018

AF and ACS/Ischaemic heart disease NOACS BACKGROUND WOEST study ATLAS ACS TIMI 51 PIONEER study REDUAL PCI study CONCLUSIONS

Meta-analysis of 4 major NOAC trials: Result for Stroke or SEE Risk Ratio (95% CI) RE-LY 0.66 (0.53 - 0.82) [150 mg] ROCKET AF 0.88 (0.75 - 1.03) ARISTOTLE 0.80 (0.67 - 0.95) ENGAGE AF-TIMI 48 0.88 (0.75 - 1.02) [60 mg] Combined 0.81 (0.73 - 0.91) [Random Effects Model] p=<0.0001 N=58,541 0.5 Favors NOAC 1 Favors Warfarin 2 Heterogeneity p=0.13 Ruff CT, et al. Lancet 2013 [in-press]

AF and ACS NOACs have transformed care for NVAF patient Very unusual now for new patient with NVAF to be given warfarin Dabigatran, Apixaban, Rivaroxaban and Edoxaban all proven non-inferior to warfarin with lower bleeding complications Choice of NOAC dependent on other co-morbidities and bleeding risk Big overlap between AF and underlying ischaemic heart disease ACS/IHD is a significant comorbidity affecting nearly 20-40% 5-10% of patients attending for PCI will have concurrent AF DAPT alone with no anticoagulant offers inferior stroke prevention than patients on anticaogulation Oral anticoagulation with no DAPT not been tested in post PCI but there would be concerns of increased stent thrombosis Previous guidance was complicated and suggested period of triple therapy for 6-12 months dependent on whether PCI was done for chronic stable symptoms or acute coronary syndrome symptoms Certain stent types more suited to more abbreviated DAPT regimes such as Biofreedom or Synergy stents

WOEST study 573 patients recently undergone PCI with AF Previous studies showed bleeding related to GI bleeding and access site bleeding perhaps implicating aspirin Compared triple therapy of Warfarin +DAPT vs double therapy of Warfarin + clopidogrel Warfarin + clopidogrel better than triple therapy in terms of bleeding 1o outcomes Study powered to look mainly at differences in bleeding Bleeding event rate was higher than expected

WOEST trial Underpowered study Lower mortality rate with Double therapy Warfarin + clopidogrel so less bleeding but no less protection from ischaemic events

ATLAS ACS 2 TIMI 51 trial Patients with recent ACS (no history of AF) were randomised to Rivaroxaban 2.5mg and 5mg bd or placebo Large study population 15,526 DAPT regime was either aspirin + clopidogrel or ticlopidine (outdated DAPT) Licence obtained for lower dose 2.5mg bd but uptake was poor

ATLAS ACS 2 TIMI 51 trial Less fatal bleeding or intra-cranial bleeding with lower dose of 2.5 vs 5mg bd More bleeding overall compared with placebo but lower mortality with low dose 2.5mg bd Licence obtained for lower dose 2.5mg bd but uptake was poor concerns re additional bleeding

Pioneer study 2124 participants with NVAF who had undergone PCI with stenting to receive, in a 1:1:1 ratio, low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1), very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months (group 2), or standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 months (group 3). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to Thrombolysis in Myocardial Infarction [TIMI] criteria or bleeding requiring medical attention). Secondary endpoint Major Adverse cardiac event (CV death/ MI/Stroke)

PIONEER Study Primary endpoint: Less bleeding with very low or low dose regime of rivaroxaban compared to Warfarin + DAPT Secondary endpoint: No difference in MACE event rate

PIONEER Study

PIONEER Study

PIONEER study conclusion Reasonable and safer to use Rivaroxaban at 15mg with clopidogrel for 1 year post PCI Give aspirin on day of PCI only Less risk of bleeding and ischaemic events when compared to warfarin and DAPT Complicated study but simple regime to follow Major drawback No data with ticagrelor/prasugrel

Re-DUAL STUDY

Re-DUAL STUDY

Re-DUAL STUDY

Redual study conclusion Benefit shown over warfarin with either dose of dabigatran 110mg or 150 mg bd Use of ticagrelor (12%) included 1-6 month worth of aspirin used dependent on type of stent used Can preferentially use synergy/ biofreedom stent to abbreviate aspirin use

Comparison of PIONEER vs RE-dual vs woest No real comparison of warfarin + clopidogrel vs NOAC + clopidogrel

Guidelines ESC 2017

conclusion Studies in progress AUGUSTUS with Apixaban ENTRUST AF PCI with edoxaban Both comparing studies NOAC + aspirin vs warfarin + aspirin Ensure adequate dose of NOAC to obtain reduction in stroke Dynamic field Single antiplatelet therapy post PCI- GLOBAL LEADERS result awaited Synergy/ Biofreedom/ abbreviated DAPT Confusing regimes NEED CLEAR GUIDANCE FROM CARDIOLOGISTS DOING PCI