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

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

3. Meta-analysis of 4 major NOAC trials: Result for Stroke or SEE
Risk Ratio (95% CI)
RE-LY
0.66 ( )
[150 mg]
ROCKET AF
0.88 ( )
ARISTOTLE
0.80 ( )
ENGAGE AF-TIMI 48
0.88 ( )
[60 mg]
Combined
0.81 ( )
[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]

4. 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

5. 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

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

7. 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DAPT regime was either aspirin + clopidogrel or ticlopidine (outdated DAPT)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

8. 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

9. 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)

10. 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

11. PIONEER Study

12. PIONEER Study

13. 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

14. Re-DUAL STUDY

15. Re-DUAL STUDY

16. Re-DUAL STUDY

17. 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

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

19. Guidelines ESC 2017

20. 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