Triple Therapy in ACS: Recent Evidences discusses studies evaluating different antithrombotic regimens for patients with atrial fibrillation who undergo percutaneous coronary intervention. The WOEST study found that dual therapy with a vitamin K antagonist (VKA) and clopidogrel reduced bleeding compared to triple therapy with VKA, aspirin, and clopidogrel, with no increase in thrombotic risk. The ISAR-TRIPLE trial found no difference in outcomes for 6 weeks versus 6 months of triple therapy following stent implantation. PIONEER AF-PCI found that dual therapy with rivaroxaban was associated with less bleeding than triple therapy with VKA, aspirin, and a

1. Triple Therapy in ACS: Recent
Evidences
Dr Amit Kumar Singh

3. Antithrombotic Therapy in Patients with AF and ACS
• Why is there any particular concern with regard to this co-morbidity?
• Patients with AF and an ACS (or stable CHD) may require PCI with
stenting.
• Need for OAC treatment to prevent stroke, and
• Need for DAPT to prevent stent thrombosis.
• Must be balanced against the increased risk of bleeding with dual or triple
antithrombotic therapy.

7. oac+pci….. ALWAYS DAPT??

8. What is the Optimal antiplatElet and
anticoagulant therapy in patients
with oral anticoagulation and
coronary StenTing (WOEST)
www.thelancet.com Published online February 13, 2013
http://dx.doi.org/10.1016/S0140-6736(12)62177-1

9. WOEST: First study with less intensive antiplatelet therapy in
combination with an anticoagulant
WOEST study:
Patients (n=573) with an indication
for OAC (≥1 year) and undergoing
PCI received:
• VKA + clopidogrel, or
• VKA + clopidogrel +ASA
One-year follow-up:
• Any/TIMI major + minor
bleeding significantly reduced in
the VKA + clopidogrel arm.
0
10
20
30
40
50
Any TIMI major
bleeding
TIMI major
+ minor
.
Dewilde et al. Lancet 2013;381:1107–1115.
Primary endpoint: bleeding events
VKA + clopidogrel
VKA + clopidogrel +ASA
Cumulativeincidence(%)
*
*
*p<0.0001
44.4%
19.4%
HR 0.36 (95% CI
0.26–0.50)

10. WOEST: significant mortality benefit reported with
dual vs triple therapy
Dewilde et al. Lancet 2013;381:1107–1115.
Cumulativeincidence(%)
0 30 60 90 120
0
2.5
5.0
7.5
6.3%
2.5%
HR=0.39 95%CI[0.16-0.93]
p=0.027
NNT = 26
VKA+
clopidogrel +ASA
VKA + clopidogrel
180 270 365
Days
All-cause mortality
• WOEST findings are hypothesis-generating – large-scale studies
are needed.

11. HOW LONG DAPT??

12. Duration of triple therapy in patients requiring
oral anticoagulation after drug-eluting stent
implantation
(ISAR-TRIPLE Trial)
Katrin A. Fiedler, Michael Maeng, Julinda Mehilli, Stefanie Schulz, Robert A. Byrne, Dirk
Sibbing, Petra Hoppmann, Simon Schneider, Massimiliano Fusaro, Ilka Ott, Steen D.
Kristensen, Tareq Ibrahim, Steffen Massberg, Heribert Schunkert, Karl-Ludwig
Laugwitz, Adnan Kastrati and Nikolaus Sarafoff
Deutsches Herzzentrum, Technische Universität, Munich, Germany; Aarhus University
Hospital, Aarhus, Denmark; Klinikum der Ludwig Maximilians Universität, Munich,
Germany; Klinikum rechts der Isar, Technische Universität, Munich, Germany
JOURNAL OF T H E AMERICAN COL LE GE OF CARD IOLOGY VOL. 65, NO. 16, 2015

13. ISAR-TRIPLE: Study Organization
DESIGN:
Prospective
Randomized
Open-label trial
September 2008 - December 2013
INCLUSION CRITERIA:
DES implantation and indication for
oral anticoagulation (AF/AFL ,
Mechanical valve , venous
thromboembolism).
MAJOR EXCLUSION CRITERIA:
Previous stent thrombosis.
DES in left main coronary artery.
614 patients with DES implantation
3 European centers
(September 2008 – December 2013)
6-week
Clopidogrel
(n=307)
6-month
Clopidogrel
(n=307)
Clinical follow up at 9 months in
606 patients (98.7%)
Aspirin and VKA
ISAR-TRIPLE

14. Months After Randomization
CumulativeIncidence(%)
0
5
10
15
20
0 1 2 3 4 5 6 7 8 9
6-month group
6-week group
Death, myocardial infarction, stent thrombosis,
stroke or TIMI major bleeding at 9 months
HR 1.14 (95%, CI 0.68 – 1.91), p=0.63
Primary Endpoint:
9.8 %
8.8 %
ISAR-TRIPLE

15. Months After Randomization
CumulativeIncidence(%)
0
5
10
15
20
0 1 2 3 4 5 6 7 8 9
Cardiac death, myocardial infarction,
stent thrombosis or ischemic stroke
HR 0.93 (0.43 - 2.05), p=0.87
TIMI major bleeding
Months After Randomization
0
5
10
15
20
0 1 2 3 4 5 6 7 8 9
HR 1.35 (0.64 - 2.84), p=0.44
Secondary Endpoints:
5.3 %
4.0 %
4.3 %
4.0 %
6-month group
6-week group
Stent thrombosis: 0.7% vs. 0%
ISAR-TRIPLE

17. CONCLUSION
• Results suggest that physicians should weigh the trade-off
between ischemic and bleeding risk when choosing the shorter
or longer duration of triple therapy.
ISAR-TRIPLE

18. CAN NOACS BE USED??

19. published on November 14, 2016, at NEJM.org.
PIONEER AF-PCI

20. PIONEER AF-PCI
Key Inclusion and Exclusion Criteria
Key
inclusion
criteria
Key
exclusion
criteria
 Medical history of paroxysmal, persistent or
permanent NVAF.
 Undergone PCI with stent placement for primary
atherosclerotic disease.
 INR ≤2.5 at randomization.
*Including, but not limited to, platelet count <90,000/µl at screening, history of ICH, 12-month history of clinically
significant GI bleeding, non-VKA-induced elevated PT at screening, anaemia of unknown cause with a
haemoglobin level <10 g/dl (<6.21 mmol/l) or significant liver disease or liver function test abnormalities
Janssen Scientific Affairs, LLC. 2016. https://clinicaltrials.gov/ct2/show/NCT01830543 [accessed 14 Oct 2016]
 Contraindication for anticoagulant or antiplatelet therapy or
unacceptable risk of bleeding*.
 History of stroke or TIA.
 CrCl <30 ml/min at screening.

21. PIONEER AF-PCI
*CrCl 30–49 ml/min: 10 mg OD; #first dose 72–96 hours after sheath removal; ‡clopidogrel (75 mg daily)
(alternative use of prasugrel or ticagrelor allowed, but capped at 15%); §ASA (75–100 mg daily) plus clopidogrel (75 mg daily)
(alternative use of prasugrel or ticagrelor allowed, but capped at 15%); ¶first dose 12–72 hours after sheath removal
1.Janssen Scientific Affairs, LLC. 2016. https://clinicaltrials.gov/ct2/show/NCT01830543 [accessed 10 Oct 2016];
2.Gibson CM et al, Am Heart J 2015;169:472–478e5; 3. Gibson CM et al, New Engl J Med 2016; doi: 10.1056/NEJMoa1611594
Design: An open-label, randomized, controlled phase IIIb safety study
Rivaroxaban 15 mg OD*# plus single antiplatelet‡
End of treatment
(12 months)
Rivaroxaban 2.5 mg BID¶
plus DAPT§
VKA (INR 2.0–3.0)¶
plus DAPT§
Rivaroxaban 15 mg OD*
plus low-doseASA
VKA plus low-doseASA
N=2,124
1:1:1
Population:
patients with
paroxysmal,
persistent or
permanent
NVAF
undergoing
PCI (with stent
placement)
R
DAPT
1 m: 15%
6 m: 35%
12 m: 50%
DAPT
1 m: 16%
6 m: 35%
12 m: 49%
Decision
for DAPT
duration:
1, 6 or 12
months
DAPT duration
(1, 6 or 12 months)

22. Both Rivaroxaban Strategies were Associated With
Significantly Improved Safety vs the VKA Strategy
Rivaroxaban 15 mg OD plus single antiplatelet vs VKAplus DAPT: HR=0.59; (95% CI 0.47–0.76); p<0.001
Rivaroxaban 2.5 mg BID plus DAPT vs VKAplus DAPT: HR=0.63 (95% CI 0.50–0.80); p<0.001
30
26.7%
Gibson CM et al, New Engl J Med 2016; doi: 10.1056/NEJMoa1611594
TIMImajor,TIMIminororbleeding
requiringmedicalattention(%)
25
20
15
10
5
0
0 30 60 90 180
Time (days)
270 360
18.0%
16.8%
Group 2 (Rivaroxaban
2.5 mg BID plus DAPT)
Group 1 (Rivaroxaban
15 mg OD plus single
antiplatelet)
Group 3 (VKA plus DAPT)
ARR
8.7%
ARR
9.9%
NNT=
12
NNT=
11

23. Efficacy was Comparable Between All Three Treatment Strategies
Trial not powered to definitively demonstrate either superiority or non-inferiority for efficacy
endpoints Gibson CM et al, New Engl J Med 2016; doi: 10.1056/NEJMoa1611594
CVdeath,MIorstroke(%)
6
4
2
0
0 30 60 90 180
Time (days)
270 360
Group 2 (Rivaroxaban
2.5 mg BID plus DAPT)
Group 1 (Rivaroxaban
15 mg OD plus single
antiplatelet)
Group 3 (VKA plus DAPT)
6.5%
6.0%
5.6%
Rivaroxaban 15 mg OD plus single antiplatelet vs VKA plus DAPT: HR=1.08; (95% CI 0.69–1.68); p=0.75
Rivaroxaban 2.5 mg BID plus DAPT vs VKA plus DAPT: HR=0.93 (95% CI 0.59–1.48); p=0.76
8

24. RE-DUAL PCI

25. Dabigatran (110 or 150 mg)
Warfarin
1 month of ASA (BMS)
3 months of ASA (DES)
*Study drug should be administered 6 hours after sheath removal and no later than ≤120 hrs post-PCI (≤72 hrs is preferable). PROBE, prospective, randomized, open, blindedend-point;
Study Design: Multicenter, randomized,
open-label trial following a PROBE design
R
Randomization
≤120 hours
post-PCI* 6-month minimum treatment duration with visits every 3 months for the first year, then
visits and telephone contact alternating every 3 months and a 1-month post-treatment
visit
Dabigatran 110 mg BID + P2Y12 inhibitor
Warfarin (INR 2.0–3.0) + P2Y12 inhibitor + ASA
Dabigatran 150 mg BID + P2Y12 inhibitor
Mean duration of
follow-up:
~14 months
R, randomization; BMS, bare metal stent; DES, drug-eluting stent. ClinicalTrials.gov: NCT02164864; Cannon et al. Clin Cardiol 2016
Patients
with AF
undergoin
g PCI with
stenting
N=2725

26. Patients were randomized based on age group
and location
Patients aged <80 years
worldwide (<70 years in
Japan), and patients
aged ≥80 years in the USA
Patients aged ≥80 years
outside the USA
(≥70 years in Japan)
Dabigatran 150 mg dual therapy
n=763
Dabigatran 110 mg dual therapy
n=769
Warfarin triple therapy
n=766
Warfarin triple therapy
n=212
n=215
Dabigatran 110 mg dual therapy

27. Inclusion and exclusion criteria
persistent or permanent NVAF
o ACS successfully treated by PCI and
stenting (BMS or DES)
that was successfully treated by elective
PCI and stenting (BMS or DES)
Key inclusion criteria o Key exclusion criteria
o Patients aged ≥18 years with paroxysmal,
o Stable CAD with ≥1 lesion eligible for PCI
• Cardiogenoic shock during hospital.
• Use of fibrinolytics within 24 hrs of
randomization that, in the investigator’s
opinion, Will put patient in high risk of
bleeding.
•Stroke or major bleeding event within
1 month prior to screening visit.
• Severe renal impairment (CrCl<30
ml/min.

28. Primary Endpoint: Time to first ISTH major
or clinically relevant non-major bleeding event
Probabilityofevent(%)
0
0 90 180 270 360 450
Time to first event (days)
540 630 720
40
35
30
10
5
Warfarin
triple therapy
HR: 0.52 (95% CI: 0.42–0.63)
Non-inferiority P<0.0001
P<0.0001
0 90 180 270 360 450
Time to first event (days)
540 630 720
40
35
30
25 25
20 20
15 Dabigatran 110 mg
dual therapy
15
10
5
0
Dabigatran 150 mg
dual therapy
Full analysis set presented. HRs and Wald CIs from Cox proportional-hazard model. For the dabigatran 110 mg vs warfarin comparison, the model is stratified by age, non-elderly vs elderly
(<70 or ≥70 in Japan and <80 or ≥80 years old elsewhere). For the dabigatran 150 mg vs warfarin comparison, an unstratified model is used, elderly patients outside the USA are excluded. Non-
inferiority P value is one sided (alpha=0.025). Wald two-sided P value from (stratified) Cox proportional-hazardmodel (alpha=0.05)
Warfarin
triple therapy
HR: 0.72 (95% CI: 0.58–0.88)
Non-inferiority P<0.0001
P=0.002
15.4%
26.9%
20.2%
25.7%

31. 13.7%
13.4%

32. Conclusion
•RE-DUAL PCI trial showed that two different regimens of full-dose
anticoagulation therapy with dabigatran (either 110 mg or 150 mg
twice daily) plus a P2Y12 inhibitor (clopidogrel or ticagrelor) resulted
in a risk of major or CRNMB events that was significantly lower than
the risk with triple therapy with warfarin.
•Dual therapy with dabigatran was noninferior to triple therapy with
warfarin with respect to the composite efficacy end point of
thromboembolic events, death, or unplanned revascularization.

34. • Neither trial was designed to assess
whether the lower incidence of
bleeding was due to :
 Use of the standard or reduced
doses of the new oral
anticoagulants or
 To the removal of aspirin
therapy.

35. VKA
(INR 2–3)
Apixaban 5 mg BID
Apixaban 2.5 mg BID in selected patients
Randomize
n=4614
patients
INCLUSION
• >18 years;
• AF (prior, persistent, permanent or
paroxysmal):
–Physician decision for OAC ; &
• ACS or PCI
–Planned P2Y12 inhibitor for ≥6 months
EXCLUSION
• Contraindication to DAPT
• Other reason for VKA
(prosthetic valve, moderate / severe
mitral stenosis)
• Renal insufficinecy, bleeding.
Trial Design
Aspirin for all on the day of ACS or PCI
Aspirin versus placebo after randomization
Open
Label
Aspirin Placebo
Double
Blind Aspirin Placebo
Double
Blind
Lopes RD, et al. Am Heart J. 2018;200:17-23.

37. VITAMIN K
ANTAGONIST
+
ASPRIN
(1123)
APIXABAN
+
ASPRIN
(1145)
VITAMIN K
ANTAGONIST
+
PLACEBO
(1126)
APIXABAN
+
PLACEBO
(1143)
2 X 2 FACTORIAL DESIGN
ASPRIN
PLACEBO
VITAMIN K
ANTAGONIST
APIXABAN

38. Participating
Countries
&
Number of
Patients

39. Primary Outcome
• ISTH major bleeding:
 Results in death.
 Occurs in critical area or organ.
 Results in hemoglobin drop ≥2 g/dL.
 Requires transfusion of ≥2 units of whole blood or packed red blood cells.
Lopes RD, et al. Am Heart J. 2018;200:17-23.
Clinically Relevant Non-major Bleeding(CRNMB):
 Results in hospitalization.
 Requires medical / surgical evaluation or intervention.
 Requires physician-directed change in antithrombotic regimen.

40. Secondary Outcomes
 Death or Hospitalization.
 Death or Ischemic Events:
– Stroke, MI , stent thrombosis (definite or probable),
urgent revascularization.
Lopes RD, et al. Am Heart J. 2018;200:17-23.

41. Baseline
Characteristics
Total (N=4614)
Age, median (25th, 75th), years 70.7 (64.2, 77.2)
Female, % 29.0
CHA2DS2-VASc score, mean (SD) 3.9 (1.6)
HAS-BLED score, mean (SD) 2.9 (0.9)
Prior OAC, % 49.0
P2Y12 inhibitor, %
Clopidogrel 92.6
Prasugrel 1.1
Ticagrelor 6.2
Number of days from ACS/PCI to
randomization, mean (SD)
6.6 (4.2)
Qualifying index event, %
ACS and PCI 37.3
ACS and no PCI 23.9
Elective PCI 38.8

42. VKA: 14.7%
Apixaban: 10.5%
Major / CRNM Bleeding
Apixaban vs. VKA
HR 0.69, 95% CI 0.58–0.81
P<0.001 for non-inferiority
P<0.001 for superiority
ARR=4.2%
NNT=24
ARR: absolute risk reduction
NNT: number needed to treat

43. Placebo: 9.0%
Aspirin: 16.1%
Major / CRNM Bleeding
Aspirin vs. Placebo
HR 1.89, 95% CI 1.59–2.24
P<0.001
ARI=7.1%
NNH=14
ARI: absolute risk increase
NNH: number needed to harm

44. VKA + Aspirin (18.7%)
Apixaban + Aspirin (13.8%)
Apixaban + Placebo (7.3%)
VKA + Placebo (10.9%)
Major / CRNM Bleeding
Apixaban + Placebo
vs. VKA + Aspirin:
11.4% absolute risk
reduction (NNT=9)

45. Apixaban: 23.5%
VKA: 27.4%
Death / Hospitalization
Apixaban vs. VKA
HR 0.83, 95% CI 0.74–0.93
P=0.002
ARR=3.9%
NNT=26
ARR: absolute risk reduction
NNT: number needed to treat

46. Aspirin: 26.2%
Placebo: 24.7%
Death / Hospitalization
Aspirin vs. Placebo
HR 1.08, 95% CI 0.96–1.21
P=0.20

47. VKA + Placebo (27.3%)
Apixaban + Placebo (22.0%)
Apixaban + Aspirin (24.9%)
VKA + Aspirin (27.5%)
Death / Hospitalization
Apixaban + Placebo
vs. VKA + Aspirin:
5.5% absolute risk
reduction (NNT=18)

48. Ischemic Outcomes
Apixaban vs. VKA
Endpoint
Apixaban
(N=2306)
VKA
(N=2308)
HR
(95% CI)
Death / Ischemic Events (%) 6.7 7.1
0.93 (0.75–
1.16)
Death (%) 3.3 3.2 1.03 (0.75–1.42)
CV Death (%) 2.5 2.3 1.05 (0.72–1.52)
Stroke (%) 0.6 1.1 0.50 (0.26–0.97)
Myocardial Infarction (%) 3.1 3.5 0.89 (0.65–1.23)
Definite or Probable Stent
Thrombosis (%)
0.6 0.8 0.77 (0.38–1.56)
Urgent Revascularization (%) 1.7 1.9 0.90 (0.59–1.38)
Hospitalization (%) 22.5 26.3 0.83 (0.74–0.93)

49. Ischemic Outcomes
Aspirin vs. Placebo
Endpoint
Aspirin
(N=2307)
Placebo
(N=2307)
HR
(95% CI)
Death / Ischemic Events (%) 6.5 7.3
0.89 (0.71–
1.11)
Death (%) 3.1 3.4 0.91 (0.66–1.26)
CV Death (%) 2.3 2.5 0.92 (0.63–1.33)
Stroke (%) 0.9 0.8 1.06 (0.56–1.98)
Myocardial Infarction (%) 2.9 3.6 0.81 (0.59–1.12)
Definite or Probable Stent
Thrombosis (%)
0.5 0.9 0.52 (0.25–1.08)
Urgent Revascularization (%) 1.6 2.0 0.79 (0.51–1.21)
Hospitalization (%) 25.4 23.4 1.10 (0.98–1.24)

50. No Significant Interactions Between Randomization Factors
Apixaban / VKA vs. Aspirin / Placebo
• Major / CRNM Bleeding: Pinteraction = 0.64
• Death / Hospitalization: Pinteraction = 0.21
• Death / Ischemic Events: Pinteraction = 0.28

51. Statistical Analysis—Hierarchical Testing
Placebo vs. Aspirin:
Major / CRNM
BleedingSup
Death /
HospitalizationSup
Death / Ischemic
EventsSup
Apixaban vs. VKA:
Major / CRNM BleedingNI then
Sup
Death / HospitalizationSup
Death / Ischemic EventsSup
Lopes RD, et al. Am Heart J. 2018;200:17-23.

53. September 3, 2019

54. ENTRUST-AF PCI..
• Randomised.
• Multicentre.
• Open-label.
• Non-inferiority phase 3b trial with masked outcome evaluation.
• Done at 186 sites in 18 countries.
• Feb 24, 2017- May 7, 2018.

55. Inclusion criteria:
• AF requiring OAC.
• Aged at least 18 years.
• Had a successful PCI for
CAD or ACS.
Exclusion criteria:
-AF with mechanical heart
valves, moderate-to-severe
MS.
-ESRD, and other
major comorbidities .

56. Clinical F/U/C
at 3 monthly.

58. BASELINE CHARACTERISTICS

60. OUTCOMES:

64. Discussion
• The ENTRUST-AF PCI trial showed that, among patients with
AF who had successful PCI, a full-dose anticoagulation therapy
with edoxaban 60 mg once daily plus a P2Y12 inhibitor is non-
inferior to a triple therapy with VKA (aspirin given for 1–12
months) regarding the risks of major or CRNM bleeding
events at 12 months.
• The edoxaban dual therapy regimen and the triple VKA
regimen showed similar rates for the main efficacy outcome, a
composite of death from cardiovascular causes, stroke, SEE,
myocardial infarction, or definite stent thrombosis.

66. Recommendations:
What do the guidelines say about
combining OAC and platelet inhibitors?

74. General management considerations

76. Elective or stable CAD

77. NSTE-ACS including unstable angina and NSTEMI

79. Primary PCI

83. AF and elective PCI without high-risk features1
Age < 65 and CHADS2 = 0 Age ≥ 65 or CHADS2 ≥ 1
ASA + Clopidogrel
Duration: at least 1 month for BMS and at
least 3 months for DES
(and up to 12 months)
OAC2 + Clopidogrel
Duration: at least 1 month for BMS
and at least 3 months for DES
(and up to 12 months)
1 A PCI is considered high-risk based on clinical and angiographic features such as: diabetes mellitus, prior ACS, chronic renal dysfunction (creatinine clearance < 60 mL/min), prior stent
thrombosis, current smoker, multi-vessel disease, multiple stents implanted, complex bifurcation lesion, total stent length > 60 mm, chronic total occlusion intervention or bioabsorbable
vascular scaffold (BVS) implantation.
2 OAC regimens evaluated in this context include rivaroxaban 15 mg daily (10 mg in patients with renal dysfunction), dabigatran 110 mg or 150 mg BID and warfarin. If warfarin is to be used,
recommended INR target is 2.0-2.5. All patients should receive a loading dose of ASA 160 mg at the time of PCI (if previously ASA naïve). Thereafter, ASA can be discontinued as early as
the day following PCI.
3 Extended treatment with a P2Y12 inhibitor can be added to ASA if high-risk clinical or angiographic features of ischemic events develop and low risk of bleeding.
4 The dose of OAC beyond the initial period of antithrombotic therapy (up to a year after PCI) should be standard stroke prevention doses as per the CCS Atrial Fibrillation Guidelines.
Single antiplatelet therapy with either ASA or clopidogrel may be added to OAC if high-risk clinical or angiographic features of ischemic events develop and low risk of bleeding.
AF: atrial fibrillation; ASA: acetylsalicylic acid; BMS: bare-metal stent; DES: drug-eluting stent; OAC: oral anticoagulant; PCI: percutaneous coronary intervention; SAPT: single antiplatelet therapy
ASA +/- P2Y12 inhibitor3 OAC4 +/- SAPT

84. In patients with AF undergoing PCI for ACS
or elective PCI with high-risk features:
Practical tip:
• The duration of treatment with DAPT in patients with ACS (or those undergoing high
risk PCI) who also have AF with a low risk of stroke should depend on a balanced
assessment of the risk of coronary thrombotic events and bleeding. Patients at lower
risk of coronary thrombotic events and higher risk of bleeding can be considered for
shorter-duration DAPT and patients at higher risk of coronary thrombotic events and
lower risk of bleeding should be considered for longer duration of DAPT.

85. AF and PCI for ACS or high-risk1 elective PCI
Age < 65 and CHADS2 = 0 Age ≥ 65 or CHADS2 ≥ 1*
ASA + P2Y12 inhibitor2
(ticagrelor, prasugrel
preferred over clopidogrel for ACS)
Duration after PCI: Up to 12 months
Reduced OAC3 + ASA + clopidogrel
ASA: stop 1 day post PCI or any time up to
6 months4
Followed by: clopidogrel + OAC
Duration after PCI: Up to 12 months
ASA +/- P2Y12 inhibitor5
*If CHADS2 =1 and Age< 65 another option for initial treatment (especially if high-risk for ischemic events) is DAPT alone
using ASA+ticagrelor or ASA+prasugrel, similar to the recommendation for the CHADS2=0 patient
1. A PCI is considered high-risk based on clinical and angiographic features such as: diabetes, prior ACS, chronic renal dysfunction (creatinine clearance < 60 mL/min), prior stent thrombosis,
current smoker, multi-vessel coronary artery disease, multiple stents implanted, complex bifurcation lesion, total stent length > 60 mm, chronic total occlusion intervention or bioabsorbable
vascular scaffold implantation.
2. Ticagrelor and prasugrel are recommended in ACS patients, whereas clopidogrel is recommended for elective PCI.
3. Regimens evaluated in the context of triple therapy include rivaroxaban 2.5 mg BID or warfarin. If warfarin is to be used, recommended INR target is 2.0-2.5. OAC options evaluated in the
context of a dual pathway strategy include rivaroxaban 15 mg daily (plus clopidogrel) or dabigatran 110 mg/150 mg BID (plus clopidogrel).
4. DAPT will have been started as part of ACS management or prior to high risk elective PCI. ASA may be discontinued as early as the day following PCI or it can be continued longer term (eg.
1, 3 or maximum 6 months after PCI). The timing of when to discontinue ASA will vary, depending on the individual patient’s ischemic and bleeding risk.
5. A P2Y12 inhibitor can be added to ASA if high-risk clinical or angiographic features of ischemic events and low risk of bleeding.
6. The dose of OAC beyond 1 year after PCI should be standard stroke prevention doses as per the CCS Atrial Fibrillation Guidelines. Single antiplatelet therapy with either ASA or clopidogrel
may be added to OAC if high-risk clinical or angiographic features of ischemic events and low risk of bleeding.
AF: atrial fibrillation; ACS: acute coronary syndrome; ASA: acetylsalicylic acid; OAC: oral anticoagulant; PCI: percutaneous coronary intervention; DAPT: dual antiplatelet therapy; SAPT: single
antiplatelet therapy
OAC6 +/- SAPT

90. *Or maintain prasugrel or ticagrelor in selected cases based on risk–benefit
considerations. **With NOAC and ASA or clopidogrel. ***With considerations on the
type of stents implanted and complexity of treated and residual coronary artery

93. • Given the current available evidence ,it is believed that an
approach of DT with one of the NOACs and P2Y12 inhibitor
should be the default strategy in the majority of patients with
atrial fibrillation with ACS and/or PCI.
• However, in high-risk patients with stent thrombosis or
complex percutaneous intervention who are deemed to be
high risk for thrombosis and low bleeding risk a regimen of TT
for no longer than 4 weeks followed by dropping the aspirin
after that is a reasonable alternative .
• There is still a need for more large RCTs comparing various
NOACs among each other and to warfarin DT in AF patients
with ACS and/or PCI who are taking anti-platelet agents.