1. Polypharmacy Anticoagulation: AF meets PCI
David J. Moliterno, MD
Professor and Chairman
Department of Internal Medicine
The University of Kentucky
Linda and Jack Gill Heart Institute

2. Conflict of Interest/Disclosure
“Polypharmacy Anticoagulation: AF Meets PCI?”
DSMB: Jannsen Pharmaceuticals (GEMINI Study)
Research Grant: Merck (Steering Committee: TRACER and TRA2P)
Astra Zeneca (Steering Committee: TWILIGHT Study)

3. Optimal Anticoagulation—does it exist?
Bleeding
Thrombosis
intensity x duration

4. Atrial Fibrillation Most common sustained cardiac arrhythmia
Currently affects nearly 2.3 million Americans, or 1% of US population
Prevalence expected to increase 2.5x by 2050
Lifetime risk of developing AF: 1 in 4 for men and women ≥ 40 years of age
Among ACS-PCI patients, ~5% have AF
AF best managed with OAC among those needing antithrombotic therapy

5. Atrial Fibrillation ACTIVE-W: 6706 randomized patients; trial stopped
ACTIVE-A: randomized patients; median follow-up of 3.6 years
P = .01 8
Clopidogrel + ASA
Vitamin K Antagonist
Clopidogrel + ASA
ASA 7
P = .0003 6 6 5 5 4
Outcome/Year (%) 4
P < .001
Outcome/Year (%) 3
P = .001
P = .53 3
P < .001 2 2 1 1
Vascular Event
Stroke
Major Bleeding
Vascular Event
Stroke
Major Bleeding
ACTIVE Investigators. Lancet. 2006;367: N Engl J Med. 2009;360:

6. Leon MB et al. N Engl J Med 1998;339:129-1665-1671
STARS
Successful BMS to mm Vessel
N = 1,653
Aspirin 325 mg QD +
Ticlid 250 mg BID
Aspirin 325 mg QD +
Warfarin INR 2-2.5
Aspirin 325 mg QD
• 30-Day Clinical Events •
Leon MB et al. N Engl J Med 1998;339:

7. Leon MB et al. N Engl J Med 1998;339:129-1665-1671
STARS
30-Day Death, MI, TVR, ST 5% RR
P<0.01 4%
Aspirin
3.6% 3%
Aspirin + Warfarin
2.7% 2% 1%
Aspirin + Ticlopidine
0.5% 5 10 15 20 25 30
Days
Leon MB et al. N Engl J Med 1998;339:

8. Lamberts M et al. Circulation 2012;126:1185-1193
Danish Registry
Danish National Registry
11,480 subjects with AF and new MI or PCI
Categorized as single, double, triple therapies
Reviewed early and late (1 year) hospitalizations for bleeding and ischemic events
Lamberts M et al. Circulation 2012;126:

9. Lamberts M et al. Circulation 2012;126:1185-1193
Danish Registry
Crude Incidence (100 person years)
50%
*Adjusted Cox Model
40%
38.0
HR 1.15*
( )
30%
26.9
26.3
HR 1.41*
( )
20%
19.4
20.1
14.2
10%
9.7
6.9
7.0
7.0
SAPT
OAC
DAPT
OSAP TT
SAPT
OAC
DAPT
OSAP TT
Bleeding Events
Ischemic Events
Lamberts M et al. Circulation 2012;126:

10. Fiedler KA et al. J Am Coll Cardiol 2015:65:1619-1629
ISAR-TRIPLE
Patients receiving OAC undergoing DES
N = 614
OAC + ASA mg daily
Clopidogrel mg,
then 75 mg daily
6 weeks
Clopidogrel mg,
then 75 mg daily
6 months
• 9-Month Death, MI, CVA, ST, TIMI Major Bleeding •
Fiedler KA et al. J Am Coll Cardiol 2015:65:

11. Fiedler KA et al. J Am Coll Cardiol 2015:65:1619-1629
ISAR-TRIPLE
Ischemic Events
BARC ≥2 2% 4% 6% 8%
10% 5%
10%
15%
20%
25%
6 Weeks (n=307)
6 Months (n=307)
P=0.41
21.3
18.4
P=0.07
P=0.87
P=0.13
12.2
4.3
4.0
3.4
7.6
1.4
9 Months
6W to 9M
9 Months
6W to 9M
Fiedler KA et al. J Am Coll Cardiol 2015:65:

12. Dewilde et al. Lancet 2013:381:1107-1115
WOEST
What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing
PCI
OAC required ≥1 year: AF, mechanical valve
N = 573
OAC + clopidogrel 75 mg
+ ASA 81 mg
daily
OAC + clopidogrel 75 mg
daily
• 1-Year Any TIMI Bleeding •
Dewilde et al. Lancet 2013:381:

13. Dewilde et al. Lancet 2013:381:1107-1115
WOEST
Primary Outcome: Any TIMI Bleeding
50%
Triple Therapy
40%
44.4%
30%
Double Therapy
19.4%
20%
10%
HR 0.36
95% CI
P<0.0001 30 60 90
120
150
180
210
240
270
300
330
365
Days
Dewilde et al. Lancet 2013:381:

14. Dewilde et al. Lancet 2013:381:1107-1115
WOEST
Death, MI, CVA, TVR, ST
20%
17.7%
Triple Therapy
15%
10%
Double Therapy
11.3% 5%
HR 0.60
95% CI
P=0.025 30 60 90
120
150
180
210
240
270
300
330
365
Days
Dewilde et al. Lancet 2013:381:

15. Angiolillo et al. Circ Cardiovasc Intv 2016
Algorithm for AF-PCI Considerations
Washout OAC
INR ≤ 2.0 for radial
INR ≤ 1.5 for femoral
Withhold NOAC 24 hours (longer if SRI)
Avoid polypharmacy anticoagulation (GPI)
Low-dose ASA
Lower INR target
Shortened-course DAPT
Lifelong OAC (± SAPT)
Angiolillo et al. Circ Cardiovasc Intv 2016

16. Angiolillo et al. Circ Cardiovasc Intv 2016
Antithrombotic Management
Recommended Algorithm
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 et al. Circ Cardiovasc Intv 2016

17. Angiolillo et al. Circ Cardiovasc Intv 2016
Algorithm for AF-PCI Considerations
More frequent follow-up than AF alone or ACS alone or PCI alone
Specific guidance for patient and PCP
Choice, extent, duration of antithrombotic therapy may change for patient or guidelines
Throughout post-PCI course need to reconsider antiplatelet risk-benefit
Angiolillo et al. Circ Cardiovasc Intv 2016

18. Summary ~5% of ACS patients have pre-existing or soon-to- come AF
Triple therapy is associated with a 40% increased risk of clinically significant bleeding
Small RCT suggest Dual Therapy with OAC and SAPT (clopidogrel) at least as effective and safer
For longer-term care, monotherapy vs “safer” dual
Nanoparticle coated stent trial ongoing
Many ongoing or planned RCT to better understand polypharmacy best practices and how NOACs and newer P2Y12 agents fit in

19. Ongoing Clinical Trials

20. Polypharmacy Anticoagulation: AF meets PCI
David J. Moliterno, MD
Professor and Chairman
Department of Internal Medicine
The University of Kentucky
Linda and Jack Gill Heart Institute