Transcript New York State Council of Health

Challenges with
Current Antiplatelet
& Anticoagulant
Therapies
CAROLYN HEMPEL, PHARMD, BCPS
CLINICAL ASSISTANT PROFESSOR
UNIVERSITY AT BUFFALO SCHOOL OF PHARMACY
Disclosures

No financial conflicts of interests to disclose.
Objectives

Assess the advantages and disadvantages of the
different antiplatelet and oral anticoagulants (OACs)
agents

Review the evidence regarding oral antiplatelets and
NOACs

Evaluate the literature surrounding the use of “triple
therapy” (aspirin, antiplatelet, and OAC)

Recommend antiplatelet or anticoagulant regimens for
a specific patient case
AJ is a 65yo M who arrives to the ER with substernal 10/10
chest pain.
HPI: AJ describes his CP as pressure like pain that lasts for 5
minutes and gets worse with exertion. This pain has been
getting worse over the last few days until today he had the
worst pain yet. He then called 911, his EKG revealed STelevations and he was emergently brought to the cath lab. 1
DES was placed in his mid-LAD.
PMH of HTN, ischemic stroke (2 years ago), hyperlipidemia,
GERD.
Vitals: BP 138/70 HR 80 PE: No significant findings
Home medications:
Aspirin 81mg Oral Daily
Omeprazole 20mg Oral Daily
Lisinopril 20mg Oral Daily
Atorvastatin 40mg Oral Daily
What antiplatelet regimen would
you recommend for this patient?

Aspirin 81mg Oral Daily

Aspirin 81mg Oral Daily + Clopidogrel 75mg Oral Daily

Aspirin 81mg Oral Daily + Prasugrel 10mg Oral Daily

Aspirin 81mg Oral Daily + Ticagrelor 90mg Oral BID
AJ is a 65yo M who arrives to the ER with substernal 10/10
chest pain.
HPI: AJ describes his CP as pressure like pain that lasts for 5
minutes and gets worse with exertion. This pain has been
getting worse over the last few days until today he had the
worst pain yet. He then called 911, his EKG revealed STelevations and he was emergently brought to the cath lab. 1
DES was placed in his mid-LAD.
PMH of HTN, ischemic stroke (2 years ago), hyperlipidemia,
GERD, atrial fibrillation
Vitals: BP 138/70 HR 80 PE: No significant findings
Home medications:
Aspirin 81mg Oral Daily
Pantoprazole 40mg Oral Daily
Lisinopril 20mg Oral Daily
Atorvastatin 40mg Oral Daily
Metoprolol succinate 100mg Oral daily
Warfarin 4mg Oral Daily
What antiplatelet regimen would
you recommend for this patient?

Aspirin 81mg Oral Daily

Aspirin 81mg Oral Daily + Clopidogrel 75mg Oral Daily

Aspirin 81mg Oral Daily + Prasugrel 10mg Oral Daily

Aspirin 81mg Oral Daily + Ticagrelor 90mg Oral BID
What would you recommend for AJ’s
anticoagulation regimen?

Discontinue warfarin until antiplatelet regimen is discontinued,
then restart warfarin

Discontinue warfarin and begin rivaroxaban 20mg oral daily

Continue warfarin and P2Y12 inhibitor, discontinue aspirin

Discontinue warfarin and begin rivaroxaban 20mg oral daily,
discontinue aspirin

Continue warfarin, P2Y12 inhibitor, and aspirin for 6 months,
then discontinue aspirin
Acute Coronary Syndromes

Standard of Care: Dual Anti Platelet Therapy (DAPT)

Aspirin + P2Y12 Inhibitor

Goal of Treatment: Reduce recurrent ischemic
events or reinfarction and improve survival

Goal of Treatment for Stents:

Bare Metal Stent (BMS) reduce stent restenosis

Drug Eluting Stents (DES) reduce in-stent thrombosis
2013 ACC/AHA STEMI Guidelines
Antiplatelet Recommendations for Primary PCI
O’Gara PT et al JACC 2013; 61:e78-140
2014 AHA/ACC NSTE-ACS Guidelines
Antiplatelet Recommendations for Primary PCI
Amsterdam EZ et al Circulation 2014
Seems easy enough, what
are the challenges??
Challenges with current
antiplatelet therapies


New available agents

Different efficacy and safety data

Lack of education

Lack of long-term data
Drugs come with adverse effects

High bleeding risk

Cost

Optimal Duration??
Antiplatelet Agents


P2Y12 Inhibitors

Clopidogrel (Plavix®)

Prasugrel (Effient®)

Ticagrelor (Brilinta®)
PAR-1 Antagonists

Vorapaxar (Zontivity®)
Challenges with Clopidogrel


Variability in platelet inhibition

Drug-Drug interactions

Up to 30% Non responders

Genetic polymorphisms in metabolism

Prodrug that must undergo two CYP450 enzymes
conversion steps (CYP 2C19)

Heterozygous vs. homozygous

Connection of clinical outcomes debated
Role of platelet function tests or genetic testing?
Prasugrel
TRITON-TIMI
Ticagrelor
PLATO
Age
61
62
STEMI
26%
38%
PCI
99%
61%
MACE
Superior
Superior
Death
No difference
Superior
Major
Bleeding
Increased
No difference
Fatal
Increased
No difference
Similar
Similar (increased fatal)
Demographic
Results
ICH
Wallentin L et al.NEJM 2009;361:1045-57
Wiviott S et al. NEJM 2007; 357:2001-15
Clopidogrel
Prasugrel
Ticagrelor
Vorapaxar
Class
Thienopyridine
Thienopyridine
Triazolopyrimidine
PAR-1 antagonist
“Reversibility”
Irreversible
Irreversible
Reversible
Reversible
Activation
Prodrug-limited by
metabolism
Prodrug-not limited by
metabolism
Active drug
Active drug
Onset of Effect
2-4hours
30min
30min
30min
Duration of Effect
3-10 days
5-10 days
2-4 days
5-13days
600 mg loading dose
(not FDA approved)
provides faster,
greater, and more
reliable platelet
inhibition
Contraindicated in
patients with hx
CVA/TIA
Concomitant ASA
dose should be <100
mg
Contraindicated in
pts with history of
stroke, TIA or
intracranial
hemorrhage
Contraindications/
Caveats
CYP2C19 *2 or *3
alleles are poor
metabolizers and
have reduced
antiplatelet effects
Generally not
recommended in
patients age >75
years (bleeding risk)
Increased bleeding
risk if body weight <60
kg
Contraindicated if
severe hepatic
impairment
Avoid use with strong
CYP3A inhibitors* or
CYP3A inducers**
BBW Increase risk of
fatal bleeding
Has only been studied
on background
antiplatelet therapies
Clopidogrel Package Insert. Bristol-Meyers Squib 2015
Prasugrel Package Insert. Eli Lilly and Company 2015
Ticagrelor Package Insert. Astra Zeneca 2015
Vorapaxar Pakcage Insert. Merck. 2015
What is the optimal duration of
DAPT?
Capodanno D, et al. Circulation 2013;238:2785-2798.
Atrial Fibrillation

Treatment for stroke prevention is therapeutic
anticoagulation with a vitamin K antagonist or nonvitamin K antagonist

Multiple new therapies available
Dabigatran
(Pradaxa®)
Rivaroxaban
(Xarelto®)
Apixaban
(Eliquis®)
Edoxaban
(Savaysa®)
MOA
Factor IIa inhibitor
Factor Xa inhibitor
Factor Xa inhibitor
Factor Xa inhibitor
FDA
approval
stroke
prevention
2010
2011
2012
2015
FDA
approval
VTE
2014
2012
2014
2015
2014 AHA/ACC/HRS Recommendations
CHA2DS2-VASc
≥2
1
0
Recommended
antithrombotic
therapy
OAC (2B)
No therapy OR
OAC OR aspirin
(2B)
No AT therapy
(2B)
RECOMMENDATIONS FOR NON-VALVULAR ATRIAL FIBRILLATION
OAC: Oral Anticoagulant including warfarin, dabigatran, rivaroxaban,
apixaban)
Warfarin: Target INR (2—3)
Aspirin: 75mg—325mg
January CT, et al. J Am Coll Cardiol 2014;64:e1-76.
January CT, et al. J Am Coll Cardiol 2014;64:e1-76.
Challenges with Vitamin K
Antagonists

Bleeding risk

Narrow therapeutic window

Routine monitoring

Slow onset/slow offset

Drug-Drug/Drug-Food Interactions
NOACs
Pros
Cons

Wide therapeutic window

No specific antidote (yet)

Predictable anticoagulant
response

No routine monitoring

Non compliance

No coagulation assay
available

Cost

No food interactions

Less drug interactions

Rapid onset

Shorter half lives
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
Tmax
1.25—3hrs
2—4hrs
1—3hrs
1—2 hours
T1/2
12—14 hrs
5—9 hrs
8—15 hrs
10—14 hours
Pro-drug
Yes
No
No
No
Metabolism
Conjugation
Oxidation &
hydrolysis
Oxidation
and
conjugation
Conjugation
and
Oxidation
Elimination
80% Renal
excretion
66% renal
excretion
25% renal
excretion
50% renal
excretion
Protein
Binding
35%
>90%
87%
~55%
Drug
Interactions
Pgp
substrate
CYP3A4
CYP3A4
CYP 3A4
substrate
substrate
substrate
Pgp substrate Pgp substrate (minimal) Pgp
substrate
Dabigatran
RE-LY
Rivaroxaban
ROCKET-AF
Apixaban
ARISTOTLE
Edoxaban
ENGAGE-AF
Demographic Data
Age
71
73
70
72
CHADS2
2.1
3.5
2.1
2.8
Mean TTR
64%
55%
62%
68%
Superior
Non-inferior
Superior
Non-inferior
Similar
Similar
Decreased
Decreased
GI Bleeding
Increased
Increased
Similar
Increased
ICH
Decreased
Decreased
Decreased
Decreased
Trial Result Data
Stroke and SE
Major
Bleeding
Connolley S et al. NEJM. 2010; 361:1139-51
Patel MR et al. NEJM. 2011; 365:883-91
Granger CB et al. NEJM. 2011; 365:981-92
Giugliano RP et al. NEJM. 2013; 369: 2093-104
SAME-TT2R2 Scoring System
Risk Factor

Risk Scoring System to
predict which patients will
have good TTR on warfarin

TTR >70%

0-2: Predicted to do well on
warfarin (i.e. maintain good
TTR)

≥ 3: Predicted to not do well
on warfarin (i.e. maintain
poor TTR)
Points
Sex category (Female)
1
Age <60 years
1
Medical history (≥2 of
following: HTN, DM, CAD/MI,
PAD, HF, previous stroke,
pulmonary/hepatic/renal
disease
1
Treatment with interacting
drugs (e.g. amiodarone)
1
Tobacco use (within 2
years)
2
Race (i.e. non-Caucasian)
2
Poli D, et al. Intern Emerg Med. 2014; 9:443-7
What do we do with those
patients with atrial
fibrillation & ACS (or CAD
with PCI)?
“Triple therapy”
Acute
Coronary
Syndrome
Atrial
Fibrillation
2-21% of ACS patients
Optimal Management of Atrial
Fibrillation and ACS Differ

Why not use DAPT
for stroke
prevention in
atrial fibrillation?

ACTIVE W
ACTIVE W Investigators Lancet 2006; 367:1903-12
Optimal Management of Atrial
Fibrillation and ACS Differ

Why not use OAC
therapy for
treatment of ACS in
patients with stents?

STARS trial
Leon MB NEJM 1998; 339: 1665-71
Possible Combinations

Approximately 3,000 combinations of dual or triple
therapy with differing durations
Antiplatelet +Therapy
ASA + warfarin
Clopidogrel + warfarin
Prasugrel + warfarin
Ticagrelor + warfarin
ASA + NOAC
Clopidogrel + NOAC (low dose)
Clopidogrel + NOAC (high dose)
Prasugrel + NOAC
Ticagrelor + NOAC
Triple Therapy
ASA + clodidogrel + warfarin
ASA + prasugrel + warfarin
ASA + Ticagrelor + warfarin
ASA + clopidogrel + NOAC (low
dose)
ASA + clopidogrel + NOAC (high
dose)
ASA + prasugrel + NOAC
ASA + Ttcagrelor + NOAC
Where’s the data?

30 non-randomized prospective observational trials
or retrospective registry data

1 randomized controlled trial

0 trials of NOACs and antiplatelet therapy in this
population


2 Randomized placebo controlled trials in ACS
population
Ongoing future studies
Triple Therapy Increases
Bleeding

Adjusted risk of nonfatal and fatal bleeding in patients treated
with aspirin, clopidogrel, and/or vitamin K antagonists after first
MI

Compared with aspirin alone, triple therapy is associated with
3-4 fold increased risk of fatal and nonfatal bleeding
Sorensen R Lancet 2009; 374:1967-74
WOEST Trial: What is the optimal antiplatelet and
anticoagulant therapy in patients with OAC and
stenting
Open label, multicenter, randomized trial
Long term OAC + indication for PCI
N=573
Double therapy
Triple therapy
N=279
N=284
Primary Endpoint: Any bleeding episode within 1 year
Secondary Endpoint: Composite endpoint of death, MI, or stroke
Median Duration Follow up = 365 days
Dewilde WM Lancet 2013; 381:1107-1115
WOEST: Primary Endpoint Results

19.4% versus 44.4%
in the double
versus triple
therapy group

Statistically
significant

This was mainly
driven by minor
bleeds (no
difference in
severe or major
bleeds)
Dewilde WM Lancet 2013; 381:1107-1115
WOEST: Secondary Endpoints
Dewilde WM Lancet 2013; 381:1107-1115
WEOST: Limitations

Small study—unable to assess differences in
ischemic events/outcomes

Only 70% percent of patients had AF

85% of patients had a CHADS2 ≥ 2

73% Femoral approach for PCI

65% Patients with drug eluting stent
Dewilde WM Lancet 2013; 381:1107-1115
What about “triple therapy”
using NOACs?
4 Phase II Dose ranging studies in ACS Patients
(dabigatran, rivaroxaban, apixaban, darexaban) lead
to 2 Phase III studies
ATLAST-ACS 2 TIMI 51: Study Design
Randomized, Placebo controlled
ACS with either DM or previous MI
N=15,526
Rivaroxaban
2.5mg BID
Rivaroxaban
5mg BID
N=5174
N=5176
Placebo
N=5176
Primary Efficacy Endpoint: Composite death from CV causes, MI or stroke
Primary Safety Endpoint: Non-CABG TIMI related major bleeding
Median Duration Follow up = 13.1 months
Mega JL. NEJM. 2012; 366:9-19
ATLAS ACS:
Primary Efficacy
Endpoint
Rivaroxaban
significantly reduced
the primary efficacy
end point with rates of
8.9% and 10.7%
(p=0.008)
Cardiovascular death
was significantly
different with no
difference in MI or
stroke
NNT = 56 patients over
2 years
Mega JL. NEJM. 2012; 366:9-19
ATLAST ACS: Primary Safety

Rivaroxaban significantly increased rate of TIMI
major bleeding that was not CABG related

2.1% versus 0.6% (p<0.001)

There was increased TIMI minor bleeding and TIMI
bleeding that required medical attention in both
rivaroxaban groups

Similar rates of fatal bleeding in both rivaroxaban
groups compared to placebo
Mega JL. NEJM. 2012; 366:9-19
APPRAISE-2: Study Design
Randomized, Double blind, placebo controlled
ACS patients with 2 additional risk factors
N=7,392
Apixaban 5mg BID
Placebo
N=3,705
N=3,687
Primary Efficacy Endpoint: Cardiovascular death, MI or stroke
Primary Safety Endpoint: TIMI Major bleeding
Median Duration Follow up = 241 days (terminated early)
Alexander JH. NEJM. 2011; 367:699-708
APPRAISE-2:
Primary Efficacy
Endpoint
A total of 279 patients
(7.5%) assigned to
apixaban
A total of 293 patients
(7.9%) assigned to
placebo group
No statistical
difference (p=0.52)
Alexander JH. NEJM. 2011; 367:699-708
APPRAISE-2:
Primary Safety
Endpoint
A total of 46 patients
(1.3%) in apixaban
group
NNH=125
A total of 18 patients
(0.5%) in apixaban
group
A greater number of
fatal and intracranial
bleeding occurred in
the apixaban group
Alexander JH. NEJM. 2011; 367:699-708
Other Differences:
Full dose versus low dose of therapy
Higher risk population in APPRAISE-2
Which population is more similar to our AF high risk population?
Caterina RD. JACC. 2012; 59:1413-1425
Limitations with current data

No actual studies to assess the risk of stroke in AF patients
post MI with NOACS

The only P2Y12 inhibitor that was studied was clopidogrel

Multiple different algorithms


Drug therapies

Duration

Population included/excluded
Bare metal stents versus Drug eluting stents
Future Studies?
RE-DUAL PCI Evaluation of Dual Therapy with Dabigatran versus
Triple Therapy with Warfarin in patients with AF that undergo PCI with
stenting
Dates
July 2014—July 2017
Study Type
Prospective, randomized, open-label, blinded endpoint
(PROBE) trial
Primary endpoint
Time to death of first thrombotic event (composite)
Time to first TIMI major bleeding
Secondary
endpoint
Time to event for individual outcomes (CV death, all death,
Stroke, stent thrombosis, MI)
Trial Arms
Dabigatran 110mg BID + Clopidogrel/Ticagrelor
Dabigatran 150mg BID + Clopidogrel/Ticagrelor
Warfarin (goal INR 2-3) + Clopidogrel/Ticagrelor + ASA (ASA
discontinued at 1 or 3 months for BMS or DES)
PIONEER AF-PCI Evaluation of Dual Therapy with Rivaroxaban in
patients with AF undergoing PCI
Dates
March 2013—August 2016
Study Type
Open label, randomized, controlled, multicenter trial
Primary
endpoint
Composite of TIMI major, minor, and bleeding requiring medical
attention
Secondary
endpoint
Composite of CV death, MI, stroke, and stent thrombosis
Trial Arms
Rivaroxaban 15mg + P2Y12 inhibitor for 12 months
Rivaroxaban 2.5mg BID + P2Y12 inhibitor + ASA for 1/6/12 months
followed by Rivaroxaban 15mg daily + ASA (low dose)
Warfarin (goal INR 2-3) + P2Y12 inhibitor + ASA for 1,6, or 12 months
then Warfarin (goal INR 2-3) plus ASA (low dose)
2014 AHA ACC NSTE-ACS
Guidelines
Recommendations Regarding “Triple Therapy”


Class I Level of Evidence C

Duration of vitamin K antagonist, aspirin, and P2Y12 inhibitor
should be minimized to the shortest time to limit excessive
bleeding

Proton pump inhibitors should be used in patients with history of
GI bleed
Class IIa Level of Evidence C


Proton pump inhibitors for patients who don’t have a history of
GI bleed
Class IIb Level of Evidence C

It is reasonable to target an INR of 2-2.5
2014 European Consensus
Document
Patients with non-valvular atrial fibrillation
STEP 1
Stroke risk
CHA2DS2-VASc
STEP 2
Bleeding risk
HAS-BLED
STEP 3
Clinical setting
CAD/PCI or ACS
STEP 4
Antithrombotic
therapy
Lip GYH. Eur Heart Journal 2014; 35:3155-3179
CHA2DS2-VASc for estimating risk
of stroke

CHA2DS2-VASc: Maximum 9 points
Score
TE rate

C = CHF/LV dysfunction (1 point)
0
0

H = HTN (1 point)
1
0.6%

A = Age >75 yo (2 points)
2
1.6%

D = Diabetes (1 point)
3
3.9%

S = Stroke/TIA (2 points)
4
1.9%

V = Vascular disease (1 point)
5
3.2%

A = Age 65-74 (1 point)
6
3.6%

S = Sex—female (1 point)
7
8%
8
11%
9
100%
Lip GYH. Chest 2010; 137:263-272
HAS-BLED Score for Estimating
Bleeding

HAS-BLED: Maximum 7 points
Score
Major
bleeding
rate
0
0.9%
1
3.4%
2
4.1%

H = Hypertension (uncontrolled)

A = Abnormal renal/liver function

S = Stroke

B = Bleeding history/predisposition

L = Labile INR (TTR <60%)

E = Elderly >65yo
3
5.8%

D = Drugs/alcohol
4
8.9%
5
9.1%
Lip GYH et al. J Am All Cardiology 2011; 57: 173-80
Pisters et al. Chest 2010; 138(5):1093-100
Lip GYH. Eur Heart Journal 2014; 35:3155-3179
What is the Pharmacists Role?

Question the physician

Educate the patients of bleeding risk

Discuss optimal Duration

Transitions of Care

Ensure these drugs are prescribed by the same
provider

Ensure patient’s are going to the follow up
appointments

Ensure that these patient’s aren’t on lifetime “triple
therapy”
AJ is a 65yo M who arrives to the ER with substernal 10/10
chest pain.
HPI: AJ describes his CP as pressure like pain that lasts for 5
minutes and gets worse with exertion. This pain has been
getting worse over the last few days until today he had the
worst pain yet. He then called 911, his EKG revealed STelevations and he was emergently brought to the cath lab. 1
DES was placed in his mid-LAD.
PMH of HTN, ischemic stroke (2 years ago), hyperlipidemia,
GERD.
Vitals: BP 138/70 HR 80 PE: No significant findings
Home medications:
Aspirin 81mg Oral Daily
Omeprazole 20mg Oral Daily
Lisinopril 20mg Oral Daily
Atorvastatin 40mg Oral Daily
What antiplatelet regimen would
you recommend for this patient?

Aspirin 81mg Oral Daily

Aspirin 81mg Oral Daily + Clopidogrel 75mg Oral Daily

Aspirin 81mg Oral Daily + Prasugrel 10mg Oral Daily

Aspirin 81mg Oral Daily + Ticagrelor 90mg Oral BID
AJ is a 65yo M who arrives to the ER with substernal 10/10
chest pain.
HPI: AJ describes his CP as pressure like pain that lasts for 5
minutes and gets worse with exertion. This pain has been
getting worse over the last few days until today he had the
worst pain yet. He then called 911, his EKG revealed STelevations and he was emergently brought to the cath lab. 1
DES was placed in his mid-LAD.
PMH of HTN, ischemic stroke (2 years ago), hyperlipidemia,
GERD, atrial fibrillation
Vitals: BP 138/70 HR 80 PE: No significant findings
Home medications:
Aspirin 81mg Oral Daily
Pantoprazole 40mg Oral Daily
Lisinopril 20mg Oral Daily
Atorvastatin 40mg Oral Daily
Metoprolol succinate 100mg Oral daily
Warfarin 4mg Oral Daily
What antiplatelet regimen would
you recommend for this patient?

Aspirin 81mg Oral Daily

Aspirin 81mg Oral Daily + Clopidogrel 75mg Oral Daily

Aspirin 81mg Oral Daily + Prasugrel 10mg Oral Daily

Aspirin 81mg Oral Daily + Ticagrelor 90mg Oral BID
What would you recommend for AJ’s
anticoagulation regimen?

Discontinue warfarin until antiplatelet regimen is discontinued,
then restart warfarin

Discontinue warfarin and begin rivaroxaban 20mg oral daily

Continue warfarin and P2Y12 inhibitor, discontinue aspirin

Discontinue warfarin and begin rivaroxaban 20mg oral daily,
discontinue aspirin

Continue warfarin, P2Y12 inhibitor, and aspirin for 6 months,
then discontinue aspirin
CHA2DS2-VASc for estimating risk
of stroke

CHA2DS2-VASc: Maximum 9 points
Score
TE rate

C = CHF/LV dysfunction (1 point)
0
0

H = HTN (1 point)
1
0.6%

A = Age >75 yo (2 points)
2
1.6%

D = Diabetes (1 point)
3
3.9%

S = Stroke/TIA (2 points)
4
1.9%

V = Vascular disease (1 point)
5
3.2%

A = Age 65-74 (1 point)
6
3.6%

S = Sex—female (1 point)
7
8%
8
11%
9
100%
Lip GYH. Chest 2010; 137:263-272
HAS-BLED Score for Estimating
Bleeding

HAS-BLED: Maximum 7 points
Score
Major
bleeding
rate
0
0.9%
1
3.4%
2
4.1%

H = Hypertension (uncontrolled)

A = Abnormal renal/liver function

S = Stroke

B = Bleeding history/predisposition

L = Labile INR (TTR <60%)

E = Elderly >65yo
3
5.8%

D = Drugs/alcohol
4
8.9%
5
9.1%
Lip GYH et al. J Am All Cardiology 2011; 57: 173-80
Pisters et al. Chest 2010; 138(5):1093-100
Lip GYH. Eur Heart Journal 2014; 35:3155-3179
What would you recommend for AJ’s
anticoagulation regimen?

Discontinue warfarin until antiplatelet regimen is discontinued,
then restart warfarin

Discontinue warfarin and begin rivaroxaban 20mg oral daily

Continue warfarin and P2Y12 inhibitor, discontinue aspirin

Discontinue warfarin and begin rivaroxaban 20mg oral daily,
discontinue aspirin
Summary

Challenges with or original antiplatelet and anticoagulant
therapies (clopidogrel and warfarin) have led to the
development of new and novel therapies

New therapies have introduced medications with similar
better efficacy results BUT each agent has their own
caveats and specific population tested

The use of “triple therapy” has a lot of conflicting data

Need additional randomized controlled trial data for this AF
+ ACS population

No evidence for “triple therapy” using any antiplatelet
agent besides clopidogrel