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(Stroke. 2008;39:1399.)
© 2008 American Heart Association, Inc.

Cochrane Corner

Oral Anticoagulants Versus Antiplatelet Therapy for Preventing Stroke in Patients With Nonvalvular Atrial Fibrillation and No History of Stroke or Transient Ischemic Attacks

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

	Introduction

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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.

	Objectives

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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).

	Search Strategy

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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.

	Selection Criteria

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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.

	Data Collection and Analysis

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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.

	Main Results

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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).

View larger version (14K): [in this window] [in a new window]   Figure. Effect of anticoagulation versus antiplatelet therapy on ischemic stroke (fatal and nonfatal).

	Reviewers’ Conclusions

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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.

	Implications for Practice

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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

	Implications for Research

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
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.

	Acknowledgments

 
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.

	References

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions Implications for Practice Implications for Research References

 
1. 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/Free Full Text]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. Aguilar MI, Hart RG, Pearce L. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks. In: Cochrane Database of Systematic Reviews. 2007. AN:00075320-100000000-04952.

8. 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] [Order article via Infotrieve]

9. 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]

10. 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] [Order article via Infotrieve]

This Article Extract Full Text (PDF) All Versions of this Article: 39/4/1399    most recent STROKEAHA.107.500363v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Aguilar, M. I. Articles by Hart, R. Search for Related Content PubMed PubMed Citation Articles by Aguilar, M. I. Articles by Hart, R. Related Collections Primary prevention Coumarins Other anticoagulants Platelet function inhibitors Embolic stroke Anticoagulants Antiplatelets