Stroke. 2008;39:1399-1400
Published online before print March 6, 2008,
doi: 10.1161/STROKEAHA.107.500363
(Stroke. 2008;39:1399.)
© 2008 American Heart Association, Inc.
Oral Anticoagulants Versus Antiplatelet Therapy for Preventing Stroke in Patients With Nonvalvular Atrial Fibrillation and No History of Stroke or Transient Ischemic Attacks
Maria I. Aguilar, MD
Robert Hart, MD
From the Mayo Clinic Arizona (M.I.A.), Phoenix, Ariz; University of Texas Health Science Center (R.G.H.), San Antonio, Tex.
Correspondence to Maria I. Aguilar, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ, US 85054. E-mail aguilar.maria{at}mayo.edu
Graeme J. Hankey MD, FRCP Section Editor:
Key Words: anticoagulant • antiplatelet • aspirin • atrial fibrillation • stroke • warfarin
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Introduction
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Nonvalvular atrial fibrillation (AF) is a common cardiac arrhythmia,
affecting about 0.7% of the general population.
1,2 Its prevalence
increases with age; about 5% of people over age 65 years and
10% of people over the age of 80 years experience AF.
1
Nonvalvular AF carries an increased risk of stroke mediated by embolism of stasis-precipitated thrombi originating in the left atrial appendage. Both oral anticoagulants and antiplatelet agents have proven effective for stroke prevention in many patients at high risk for vascular events (ie, for secondary prevention), but primary stroke prevention in patients with nonvalvular AF potentially merits separate consideration because of the suspected cardioembolic mechanism of most strokes in AF patients.
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Objectives
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We set out to characterize the relative effect of long-term
oral anticoagulant treatment compared with antiplatelet therapy
on major vascular events in patients with nonvalvular AF and
no history of stroke or transient ischemic attack (TIA).
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Search Strategy
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We searched the Cochrane Stroke Group Trials Register (June
2006). We also searched the Cochrane Central Register of Controlled
Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE
(1966 to June 2006) and EMBASE (1980 to June 2006). We contacted
the Atrial Fibrillation Collaboration and experts working in
the field to identify unpublished and ongoing trials.
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Selection Criteria
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All unconfounded, randomized trials in which long-term (>12
weeks) adjusted-dose oral anticoagulant treatment was compared
with antiplatelet therapy in patients with chronic nonvalvular
AF.
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Data Collection and Analysis
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Two physician authors independently assessed trials for inclusion,
recorded quality parameters, and extracted data. The Peto method
was used for combining odds ratios after assessing for heterogeneity.
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Main Results
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Eight randomized trials, including 9598 patients, tested adjusted-dose
warfarin versus aspirin (in dosages ranging from 75 to 325 mg/d;
6 trials, 2178 patients), aspirin plus clopidogrel (1 trial,
6706 patients), or trifusal (1 trial, 479 patients) in AF patients
without prior stroke or TIA. The mean overall follow-up was
1.9 years/participant. Oral anticoagulants were associated with
lower risk of all stroke (odds ratio [OR] 0.68, 95% CI 0.54
to 0.85), ischemic stroke (OR 0.53, 95% CI 0.41 to 0.68) and
systemic emboli (OR 0.48, 95% CI 0.25 to 0.90). All disabling
or fatal strokes (OR 0.71, 95% CI 0.59 to 1.04) and myocardial
infarction (OR 0.69, 95% CI 0.47 to 1.01) were substantially,
but not statistically significantly, reduced by oral anticoagulants.
Vascular death (OR 0.93, 95% CI 0.75 to 1.15) and all-cause
mortality (OR 0.99, 95% CI 0.83 to 1.18), were similar with
these treatments. Intracranial hemorrhages (OR 1.98, 95% CI
1.20 to 3.28) were increased by oral anticoagulation relative
to antiplatelet therapy.
The Figure shows the effect of anticoagulation versus antiplatelet therapy on ischemic stroke (fatal and nonfatal).
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Reviewers’ Conclusions
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Adjusted-dose warfarin and related oral vitamin K antagonists
reduce stroke, disabling stroke and other major vascular events
for those with nonvalvular AF by about one third when compared
with antiplatelet therapy. Based on meta-analysis of other trials,
antiplatelet agents reduce stroke by about 20% in AF patients
compared with no therapy, offering a less efficacious therapeutic
option for those deemed not eligible for anticoagulation therapy.
Considering the results from all available relevant randomized
trials, oral anticoagulants reduce stroke in AF patients more
effectively than antiplatelet agents, reducing ischemic strokes
by half and doubling the less frequent hemorrhagic strokes for
an overall net reduction. The threshold of absolute benefit
that warrants anticoagulation instead of antiplatelet therapy
remains controversial and depends on patient’s preferences
and availability of optimal anticoagulation monitoring.
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Implications for Practice
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Adjusted-dose warfarin and related oral anticoagulants reduce
stroke and other major ischemic vascular events for those with
nonvalvular AF, and the effect is still significant (about 40%)
when compared with the effect of aspirin (which reduces stroke
by about 20% in AF patients). Adjusted-dose warfarin offers
larger, more predictable reductions in stroke for AF patients
who can safely receive it.
3 Most guidelines recommend adjusted-dose
warfarin for AF patients at high risk for stroke and aspirin
for those deemed at low risk or for those who cannot safely
receive adjusted-dose warfarin. Stroke risk stratification schemes
have been developed and validated for AF patients that allow
reliable classification of risk.
4–6
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Implications for Research
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Antithrombotic agents that are more efficacious than aspirin
and that are safer and easier to use than adjusted-dose warfarin
are needed for the growing population of elderly patients with
nonvalvular AF. A substantial unmet need remains for those who
are unable to receive oral anticoagulants, yet whose stroke
risk remains unacceptably high with antiplatelet therapy.
Note: For full review please refer to Issue 3, 2007 of The Cochrane Library.7
The Chinese ATAFS8, the WASPO9, and the BAFTA10 trials were not available at the time of completion of this systematic review.
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Acknowledgments
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Disclosures
R.H. has served as a consultant to Astellas Pharmaceuticals and to Sanofi-Aventis/Bristol-Myers Squibb for design of clinical trials involving patients with atrial fibrillation.
Received July 30, 2007;
accepted August 9, 2007.
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References
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- Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995; 155: 469–473.[Abstract]
- Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001; 285: 2370–2375.[Abstract/Free Full Text]
- van Walraven C, Hart RG, Singer DE, Laupacis A, Connolly S, Petersen P, Koudstaal PJ, Chang Y, Hellemons B. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA. 2002; 288: 2441–2448.[Abstract/Free Full Text]
- Gage BF, van Walraven C, Pearce L, Hart RG, Koudstaal PJ, Boode BS, Petersen P. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. [see comment]. Circulation. 2004; 110: 2287–2292.[Abstract/Free Full Text]
- Go AS, Hylek EM, Chang Y, Phillips KA, Henault LE, Capra AM, Jensvold NG, Selby JV, Singer DE. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? JAMA. 2003; 290: 2685–2692.[Abstract/Free Full Text]
- Hart RG, Halperin JL, Pearce LA, Anderson DC, Kronmal RA, McBride R, Nasco E, Sherman DG, Talbert RL, Marler JR; Stroke Prevention in Atrial Fibrillation Investigators. Lessons from the Stroke Prevention in Atrial Fibrillation trials. Ann Intern Med. 2003; 138: 831–838.[Abstract/Free Full Text]
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- Antithrombotic Therapy in Atrial Fibrillation Study Group. [The randomized study of efficacy and safetry of antithrombotic therapy in non valvular atrial fibrillation: warfarin compared with aspirin. Zhonghua Xin Xue Guan Bing Za Zhi. 2006; 34: 295–298.[Medline]
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- Rash A, Downes T, Portner R, Yeo WW, Morgan N, Channer KS. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). [see comment]. Age & Ageing. 2007; 36: 151–156.[Abstract/Free Full Text]
- Mant J, Hobbs FD, Fletcher K, et al; on behalf of the BAFTA investigators and the Midland Research Practices Network. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged study, BAFTA): a randomized controlled trial. Lancet. 2007; 370: 493–503.[CrossRef][Medline]
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Introduction
Objectives