Concomitant Antiplatelet and OAC Tx:
Real-World Practice
• In the US, ~800,000 AF patients are on concomitant
OAC and antiplatelet tx1
• Patients on chronic OAC with CAD are 7x more likely to
receive concomitant antiplatelet tx2
• Addition of single antiplatelet tx to OAC increases risk of
major bleeding by >40%3
• Addition of double antiplatelet tx to OAC increases risk
of major bleeding by ~300%4,5
• Majority of studies evaluated warfarin; novel OACs may
offer theoretical benefits in concomitant antiplatelet
setting5,6
1Douketis
JD. Thromb Res. 2011;127:513-517; 2Johnson SG. Chest. 2007;131:1500-1507; 3Dentali F. Arch
Intern Med. 2007;167:117-124; 4Hansen ML. Arch Intern Med. 2010;170:1433-1441; 5Dans A. Circulation. 2012
Dec 27 [ePub ahead of print]; 6Sinnaeve PR. Circulation 2012 Dec 27 [ePub ahead of print]
RE-LY: Main Results
Warfarin
(n=6022)
Dabigatran 110 mg BID
(n=6015)
Rate
(%/y)
Rate
(%/y)
RR (95% CI)
Stroke/SE
1.7
1.53
Hemorrhagic
stroke
0.38
Major
bleeding
Intracranial
bleeding
Dabigatran 150 mg BID
(n=6076)
vs warfarin
P
Rate
(%/y)
vs warfarin
RR (95% CI)
P
0.91 (0.74–1.11)
.34
1.1
0.66 (0.53–0.82)
<.001†
0.12
0.31 (0.17–0.56)
<.001
0.10
0.26 (0.14–0.49)
<.001
3.4
2.7
0.80 (0.69–0.93)
.003
3.1
0.93 (0.81–1.07)
.31
0.74
0.23
0.31 (0.20–0.47)
<.001
0.30
0.40 (0.27–0.60)
<.001
Study Design: PROBE (N = 18,113)
Primary Efficacy: All stroke or systemic embolism
Primary Safety: Major bleeding
Mean Follow-up: 2 years
Inclusion: NVAF and ≥ 1 risk factor*
Mean CHADS2 Score: 2.1 (CHADS2 ≥3: 33%)Mean TTR: 64%
*Risk factors: prior stroke/TIA; LVEF < 40%; NYHA Class ≥ II; aged ≥ 75 years, or aged 65-74 years with
DM, HTN, or CAD
†for both inferiority and superiority
Connolly SJ, et al. N Engl J Med. 2009;361:1139-1151
Effects of Adding Single or Dual Antiplatelet Tx on Major
Bleeding in RE-LY
• Regardless of OAC-type, addition of antiplatelet tx ↑ bleeding risk
• Single antiplatelet tx added to warfarin ↑ bleeding risk by 60%
• Adding dual antiplatelet tx to warfarin ↑ bleeding risk by 230%
• Dabigatran retained its benefit over warfarin in patients on antiplatelet tx
Major Bleed
2.8
4.6
2.6
2.2
0
1
2
4.3
4
6.3
......HR = 2.22 (95% Cl: 1.49, 3.30)
HR = 1.56 (95% Cl: 1.54, 1.24)
5.5
3.8
3
HR = 1.63 (95% Cl: 1.32, 2.02)
......HR = 2.10 (95% Cl: 1.37, 3.21)
HR = 1.48 (95% Cl: 1.17, 1.87)
5.4
5
......HR = 1.64 (95% Cl: 1.05, 2.56)
6
7
8
Event Rate (%/year)
Patients on Warfarin
No Antiplatelet
Single Antiplatelet
Dual Antiplatelet
Patients on DE 150
No Antiplatelet
Single Antiplatelet
Dual Antiplatelet
Patients on DE 110
No Antiplatelet
Single Antiplatelet
Dual Antiplatelet
Dans A, et al. Circulation. 2012 Dec 27 [ePub ahead of print]; Slide courtesy of Stuart J. Connolly, MD
Recommendations for Concomitant
Antiplatelet + OAC Tx with Stent Placement:
The North American Perspective
Stent
Type
Patients with AF at Moderate/High Stroke Risk (CHADS2 ≥ 1) at:
Low ST and
bleeding risk
High ST and low
bleeding risk
Any ST risk and
high bleeding risk
Triple therapy for ≥6
months, then OAC +
SAPT for 12 months
Triple therapy for ≥1
month, then OAC +
SAPT for 12 months
BMS
Triple therapy for ≥1
month, then OAC +
SAPT for 12 months
DES
Triple therapy for ≥6
Triple therapy for 12
months, then OAC +
months
SAPT for 12 months
Not recommended
After 12 months, OAC should be resumed indefinitely.
(In patients at high risk for atherothrombotic events, including ST, continued SAPT with
OAC should be considered after 12 months)
BMS, bare-metal stent; DES, drug-eluting stent; OAC, oral anticoagulant
(warfarin); SAPT, single antiplatelet therapy (aspirin or clopidogrel); ST,
stent thrombosis; triple therapy (warfarin, aspirin, and clopidogrel)
Faxon DP. Circ Cardiovasc Interv. 2011;4:522-534
Concomitant Antiplatelet and OAC Tx:
Pearls for Practice
• Tx decisions require careful balance of benefits vs
inherent risks
• Keep concomitant durations as short as possible
– Use bare-metal stents, when possible
• Lessen intensity of anticoagulation.
– Target tighter INR for warfarin (target INR 2.0-2.5)
– Lower doses of novel OACs
– Lower doses of antiplatelet(s)
• Consider prophylactic use of proton-pump inhibitors to
reduce GI bleeding
• Avoid concomitant NSAID use
Faxon DP. Circ Cardiovasc Interv. 2011;4:522-534