NOAC in patients with Atrial

Fibrillation and Acute

Coronary Syndromes

Department of Cardiology,

Arcispedale S. Anna

University of Ferrara

Matteo Bertini, MD, PhD

Among ACS patients undergoing PCI, approximately 5% to 21% of patients have concomitant AF.

Despite overlap in the occurence of these syndromes, the pharmacotherapies used to manage AF and ACS differ

Atrial fibrillation and PCI

Rubboli et al., J Interv Cardiol 2009

The management of AF patients who

undergo stent placement for an ACS is

challenging

VKA + antiplatelets

Thrombotic riskHaemorragic risk

-AF-related ischaemic stroke-Bleeding associated with

antithrombotic therapy-Stent thrombosis

Ischaemic stroke associated with warfarin, aspirin and clopidogrel in patients with AF

Hansen et al. Arch Int Med 2010; 170: 1433-1441

n = 82854

Bleeding associated with warfarin, aspirin and clopidogrel in patients with AF

n = 82854

Hansen et al. Arch Int Med 2010; 170: 1433-1441

TRIPLE THERAPY: clinical evidences

WOEST Trial

Primary outcome: any bleeding episode within 1 year of PCI

ISAR-TRIPLE

• 600 pts

• Indication to VKA+DES (ACS or elective)

• 9-month follow-up

• Composite endpoint : death, MI, stroke, ST, TIMI-bleeding

NOACS in association with DAPT (aspirin+clopidogrel) ?

In all NOACS trials ( RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) patients wereexcluded from enrollment if receiving newP2Y12

And conversely, AF patients requiring OAC were systematically excluded from recent ACS trials.

Some data are available in non AF patients

97% patients were taking aspirin81% patients were taking aspirin plus a P2Y12-receptor inhibitor (predominantly clopidogrel)

Primary OutcomeCV Death, MI, Ischemic Stroke

Apixaban 279 (7.5%)

Placebo 293 (7.9%)

HR 0.95; 95% CI 0.80-1.11; p=0.509

APPRAISE-2

TIMI Major BleedingApixaban 48 (1.3%)

Placebo 18 (0.5%)

HR 2.59; 95% CI 1.50–4.46; p=0.001

APPRAISE-2

ATLAS ACS 2 TIMI 51

Rivaroxaban

2.5 mg bid

n=4825

Placebo

n=4821

Rivaroxaban

5 mg bid

n=4827

Event-driven study – 1002 events

Stratum 2: ASA +

thienopyridine (93%)

Rivaroxaban

2.5 mg bid

n=349

Placebo

n=355

Rivaroxaban

5 mg bid

n=349

Physician's decision to add thienopyridine or not

N=15,526*

ASA dose =

75–100 mg/day

Stratum 1: ASA

alone (7%)

Mega et al, 2011

Primary efficacy endpoint (CV death/MI/stroke)Both rivaroxaban doses, both strata

Number at risk

Placebo 5113 4307 3470 2664 1831 1079 421

Rivaroxaban 10,229 8502 6753 5137 3554 2084 831

Months after randomization

HR=0.84

(0.74–0.96)

ARR=1.7%

mITT p=0.008ITT p=0.002

NNT=56

10.7%

8.9%

2-year Kaplan–Meier estimate

Estim

ate

d c

um

ula

tive r

ate

(%

)

Rivaroxaban

Placebo

12

00 16

10

8

6

4

2

201284 24

Mega et al, 2011 ATLAS ACS 2 TIMI 51

Rivaroxaban

2.5 mg bid

(n=5115)

Rivaroxaban

5 mg bid

(n=5110)

Placebo

(n=5125)

Non-CABG TIMI major bleed

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 0.04 0.005

Fatal bleeding

K–M estimate at 2 years 0.1% 0.4% 0.2%

p value versus placebo 0.45 0.20

Fatal ICH

K–M estimate at 2 years 0.1% 0.2% 0.1%

p value versus placebo – –

Mega et al, 2011ATLAS ACS 2 TIMI 51

Safety endpoint

AF + NOAC + DAPT

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…

However….

1. Personalize antithrombotic therapy according to:

- Stroke risk (CHA2DS2 VASC)- Bleeding risk (HAS BLED)- Clinical setting (ACS vs elective)- Stent type (DES vs BMS)- Time from PCI/ACS

In practice… what to do?

2. Prefer:

- 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

In practice… what to do?

Thanks!

Thanks!

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)

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 theprimary 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 meaningfullyassess major efficacy outcomes such as stent thrombosis or death