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Combining Antiplatelet Drugs and Oral
Anticoagulant Therapy in Atrial Fibrillation:
Acute Coronary Syndromes and/or
Percutaneous Coronary Intervention/Stenting
Revisited
To the Editor:
We agree with Gorelick1 that there is little evidence that
combination aspirin and oral anticoagulant (OAC) therapy
among patients with atrial fibrillation (AF) improves stroke
prevention but, instead, increases risk of major bleeding. The
latter should come as little surprise, given the mode of action of
both drugs.
Indeed, the efficacy of OAC compared with aspirin in this
condition is overwhelmingly supported by data from clinical
trials.2 However, AF commonly associates with (cardio)vascular
disease, and frequently AF patients are still prescribed both OAC
and antiplatelet therapies in combination. In the setting of AF and
acute coronary syndromes (ACS) or coronary angioplasty/stents,
it is not infrequent for patients to be prescribed ‘triple therapy’
with OAC, aspirin and clopidogrel.
Gorelick1 provides a critique on the recent article by Flaker et
al,3 but broad similar conclusions were reported from the
FFAACS trial,4 where fluindione (an OAC) plus aspirin was
compared with fluindione alone, and no difference in thrombo-
embolism rate was reported between the 2 arms, although
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combination therapy did significantly increase bleeding rate
(13.1% versus 1.2%, P⫽0.003).
Given the rising prevalence of AF and coexistent vascular
disease, as well as increasing application of percutaneous coro-
nary angioplasty/stenting, the coprescription of OAC and anti-
platelet agents is likely to surge. The ACC/AHA/ESC 2006
Guidelines for the Management of Patients with AF5 suggest that
after angioplasty/stenting, low-dose aspirin (⬍100 mg/d) and/or
clopidogrel (75 mg/d) may be given concurrently with anticoag-
ulation to prevent myocardial ischemic events, but acknowledges
these strategies have not been thoroughly evaluated and are
associated with an increased risk of bleeding. These recommen-
dations do not give a differential management strategy in relation
to an ACS presentation or the perceived bleeding risk.
Given recent concerns over late stent thrombosis with drug
eluting stents, the likelihood of some AF patients at high risk of
stroke being coprescribed OAC plus aspirin plus clopidogrel for
12 months (or more) by some cardiologists is real, with the
associated high bleeding risk.6 Other practical management
guidance for AF patients presenting with ACS and/or need
angioplasty/stenting have tried to relate the approach to stroke
risk, associated ACS presentation, bleeding risk and/or type of
stent used7 (Table). The choice of warfarin plus clopidogrel
long-term5,7 may seem an ‘evidence free’ zone, but given data
demonstrating that the combination of OAC plus aspirin is
inadequate to prevent coronary stent thrombosis,7,8 and that OAC
alone is marginally different from ‘OAC plus aspirin’ in ACS for
reducing coronary events but increases bleeding,7,9 more pro-
spective data are urgently required.
(Stroke. 2007;38:e107-e108.)
© 2007 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
e107
Clearly, a very careful balance is needed between stroke
prevention (especially in a ‘high risk’ AF patient requiring
OAC), recurrent cardiac ischemia (eg, post-ACS and/or stent
use) and bleeding risk attributed to adding antiplatelet therapy to
OAC use.
Disclosures
None.
Timothy Watson, MRCP
Gregory Y.H. Lip, MD, FRCP
University Department of Medicine
City Hospital
Birmingham, UK
1. Gorelick PB. Combining aspirin with oral anticoagulant therapy: is this a
safe and effective practice in patients with atrial fibrillation. Stroke 2007;
38:1652–1654.
2. Lip GYH, Edwards SJ. Stroke prevention with aspirin, warfarin and
xilmelagatran in patients with non-valvular atrial fibrillation: a systematic
review and meta-analysis. Thromb Res. 2006;118:321–333.
3. Flaker GC, Gruber M, Connolly SJ, Goldman S, Chaparro S, Vahanian A,
Halinen MO, Horrow J, Halperin JL; SPORTIF Investigators. Risks and
benefits of combining aspirin with anticoagulant therapy in patients with
atrial fibrillation: an exploratory analysis of stroke prevention using an oral
thrombin inhibitor in atrial fibrillation (SPORTIF) trials. Am Heart J.
2006;152:967–973.
4. Lechat P, Lardoux H, Mallet A, Sanchez P, Derumeaux G, Lecompte T,
Maillard L, Mas JL, Mentre F, Pousset F, Lacomblez L, Pisica G, Solbes-
Latourette S, Raynaud P, Chaumet-Riffaud P; FFAACS (Fluindione,
Fibrillation Auriculaire, Aspirin et Contraste Spontane) Investigators. Anti-
coagulant (fluindione)-aspirin combination in patients with high-risk atrial
fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et
Contraste Spontane; FFAACS). Cerebrovasc Dis. 2001;12:245–252.
5. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA,
Halperin JL, Le Heuzey J-Y, Kay GN, Lowe JE, Olsson SB, Prystowsky
EN, Tamargo JL, Wann S, Smith SC, Jacobs AK, Adams CD, Anderson
JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B,
Priori SG, Blanc J-J, Budaj A, Camm AJ, Dean V, Deckers JW, Despres
C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A,
Zamorano JL. ACC/AHA/ESC 2006 guidelines for the management of
patients with atrial fibrillation: a report of the American College of Car-
diology/American Heart Association Task Force on Practice Guidelines
and the European Society of Cardiology Committee for Practice
Guidelines (Writing Committee to Revise the 2001 Guidelines for the
Management of Patients With Atrial Fibrillation). J Am Coll Cardiol.
2006;48:e149 –246.
6. Khurram Z, Chou E, Minutello R, Bergman G, Parikh M, Naidu S, Wong
SC, Hong MK. Combination therapy with aspirin, clopidogrel and warfarin
following coronary stenting is associated with a significant risk of
bleeding. J Invasive Cardiol. 2006; 18:162–164.
7. Lip GY, Karpha M. Anticoagulant and antiplatelet therapy use in patients
with atrial fibrillation undergoing percutaneous coronary intervention: the
need for consensus and a management guideline. Chest. 2006;130:
1823–1827.
8. Karjalainen PP, Porela P, Ylitalo A, Vikman S, Nyman K, Vaittinen MA,
Airaksinen TJ, Niemela M, Vahlberg T, Airaksinen KE. Safety and
efficacy of combined antiplatelet-warfarin therapy after coronary stenting.
Eur Heart J. 2007; 28:726 –732.
9. Lip GYH, Varma C. Anticoagulation plus aspirin following acute myo-
cardial infarction: Yes or no. and if the latter, why not? Thromb Res.
2006;118:429 – 432.
DOI: 10.1161/STROKEAHA.107.492488
 e108 Letters to the Editor

Table. Suggested Management Strategy for Patients With Nonvalvular Atrial Fibrillation Requiring Anticoagulation, and Percutaneous
Coronary Intervention With Stenting*
Stroke Risk Category ‘Usual’ Strategy Recommended Perceived Potential Bleeding Risk ACS Presentation Post PCI Management
Low Aspirin 䡠䡠䡠 䡠䡠䡠 Bare metal stent—aspirin plus clopidogrel for 4
weeks, then aspirin
DES—aspirin plus clopidogrel for 6–12 months,
then aspirin
High Warfarin Low No Use bare metal stent if possible
Bare metal stent—triple therapy with warfarin,
aspirin plus clopidogrel for 2–4 weeks; then
change to warfarin plus clopidogrel for up to
month 12, then warfarin alone
DES—triple therapy with warfarin, aspirin and
clopidogrel for 3–6 (or more) months, then
warfarin plus clopidogrel for up to month 12,
then warfarin alone
Low Yes Bare metal stent or DES—triple therapy with
warfarin, aspirin and clopidogrel for 3–6 (or
more) months, then warfarin plus clopidogrel
for up to month 12, then warfarin alone
High Warfarin High† No Use bare metal stent if possible
Bare metal stent—triple therapy with warfarin,
aspirin plus clopidogrel for 4 weeks; then
change to warfarin alone
DES—triple therapy with warfarin, aspirin and
clopidogrel for 4 weeks, then warfarin plus
clopidogrel for up to month 12, then
warfarin alone
High† Yes Bare metal stent or DES—triple therapy with
warfarin, aspirin and clopidogrel for 4 weeks,
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then warfarin plus clopidogrel for up to month

12, then warfarin alone
Doses: aspirin 75 mg/day; clopidogrel 75 mg/day. Warfarin dose adjusted to target INR 2.0 –2.5.
DES indicates drug eluting stent; PCI, percutaneous coronary intervention; ACS, acute coronary syndrome.
*From Lip and Karpha,7 with permission.
†Particular attention paid to the following risk factors: (1) patients who are over 75 years of age; (2) those who were taking antiplatelet drugs or nonsteroidal
anti-inflammatory drugs; (3) those who were on multiple other drug treatments (polypharmacy); (4) those with uncontrolled hypertension; (5) those who gave a history
of bleeding (for example, peptic ulcer or cerebral haemorrhage); and (6) those with a history of poorly controlled anticoagulation therapy.