Problems and Solutions of Antiplatelet
Therapy in Combination with Oral
Anticoagulants
Marvin H. Eng, MD FSCAI FACC
Assistant Professor of Medicine
Division of Cardiology
University of Texas Health Sciences Center
San Antonio, Texas


Disclosures
• No relevant disclosures



Outcomes Related to Severity of
Bleeding

Eikenbloom JW et al.
Circulation 2006;114:774-82.


Non-Access Bleeding

Ndereppa G et al. Circ Cardiovasc Int. 2013
;6:354-351.


HAS-BLED
Predictive of Bleeding
Hypertension


Age > 75 years

1

DM

1

Stroke or TIA

2

5
0
0

1

2
3
4
CHADS2 score

5

6

Gage B et al. JAMA 2001;285:2864-70.


P=0.005

3

P=0.01
ASA
ASA + Warfarin

2

ASA + Ticlodipine
1
0
1° Endpoint

TLR

Angiographic Recurrent MI
thrombus

Leon MB et al. NEJM 1998;339:1665-71.


ASA+ Warfarin in ACS or MI
Stratified by Bleeding/Thrombotic Risk

Rothberg MB et al.
Annals of Internal Medicine
2005:143:241-250.



1.43 (1.43-1.43)

ASA + VKA

5.1%

1.94 (1.94-1.95)

Clopidogrel + VKA

12.3%

4.68 (4.64-4.74)

Triple therapy (DAPT + VKA)

12.0%

4.57 (4.55-4.61)

Sorensen R et al. Lancet 2009;374:1967-74.


Real World Patients
Rates of Stent Thrombosis

Karjalainen P. et al. EHJ 2007;28:726-732.



12.5 (8.9-17.6)

VKA + clopidogrel

4.4 (4.8-11.8)

4.6 (2.6-8.3)

7.0 (4.4-11.3)

10.3 (7.1-15.0)

VKA +ASA

4.7 (4.2-5.2)

2.3 (2.0- 2.7)

5.2 (4.7-5.8)

7.1 (6.5-7.8)

VKA

4.7 (4.1-5.4)

3.0 (2.5-3.6)

3.9 (3.3-4.6)


13.5 (12.9-14.1)

Lamberts, M et al. Circulation 2014;
129:1577-1585.


ISAR TRIPLE
Composite Endpoint and Bleeding

Fiedler K et al. TCT 2014, Washington D.C.


Triple Anticoagulation with Prasugrel
Significant Hazard for Bleeding

Saraoff, N et al. JACC 2013;61:2060-6.


Novel Anti-coagulants

De Caterina et al. JACC 2012;59:1413-25


Novel Oral Anticoagulants
Dabigatran

Direct thrombin
inhibition
Direct Xa inhibitor
Prodrug

1-4 hr
66%
5-13
66%
Y

N
1-4 hr
50%
8-15
27%
Y

De Caterina et al. JACC 2012;59:1413-25


ATLAS ACS-2 TIMI-51
Rivaroxaban+ DAPT

Mega JL et al. JACC 2013;61:1853-9.


ATLAS ACS-2 TIMI-51
Rivaroxaban+ DAPT

Mega JL et al. JACC 2013;61:1853-9.


ATLAS-ACS TIMI-51
Rivaroxaban in ACS

– Stroke
– Stent thrombosis
• ACS

• Triple therapy
– May be tolerated in good candidates
• More bleeding

– Avoid newer antiplatelet therapies (prasugrel/ticagrelor)

• Dual-therapy better for bleeding risk but thrombotic risk
still unproven.
• Role of Factor Xa and DTI in ACS