Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Review: Anticoagulants may be better than antiplatelet agents for nonfatal stroke but not other vascular or fatal events in nonrheumatic AF

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ACP J Club. 2001 Sep-Oct;135:60. doi:10.7326/ACPJC-2001-135-2-060

Related Content in this Issue
• Letter: Review: Anticoagulants may be better than antiplatelet agents for nonfatal stroke but not other vascular or fatal events in nonrheumatic AF


Source Citation

Taylor FC, Cohen H, Ebrahim S. Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation. BMJ. 2001 Feb 10;322:321-6. [PubMed ID: 11159653] (All 2001 articles were reviewed for relevancy, and abstracts were last revised in 2007.)


Abstract

Question

In patients with nonrheumatic atrial fibrillation (AF), what are the benefits and risks of long-term anticoagulation with warfarin compared with those of antiplatelet treatment with aspirin or indoprofen?

Data sources

Studies were identified by searching the Cochrane Controlled Trials Register, MEDLINE, EMBASE/Excerpta Medica, CINAHL, and SIGLE up to the end of 1999 with the terms atherosclerosis, atrial fibrillation, myocardial infarction, coronary disease, and anticoagulation and with a filter designed to retrieve randomized controlled trials. Authors were also contacted.

Study selection

Randomized controlled trials were selected if patients had nonrheumatic AF and received either anticoagulation or antiplatelet treatment for > 1 year. Trials that evaluated combined use of anticoagulation with antiplatelet drugs were excluded, as were studies that included patients with AF caused by thyrotoxicosis and mitral valve disease or those with heart-valve replacements.

Data extraction

Data were extracted on study quality; patient characteristics; intervention, including drug, dose, withdrawals, and duration; international normalized ratio (INR); and outcomes of fatal and nonfatal cardiovascular events (stroke, myocardial infarction, and thromboembolism) and adverse effects, including major bleeding events.

Main results

5 RCTs (3298 patients) met the inclusion criteria. Follow-up ranged from 12 to 42 months. The anticoagulation and antiplatelet groups did not differ for any outcomes except for a reduction in nonfatal stroke (Table).

Conclusion

Long-term anticoagulation may be more effective than antiplatelet treatment for preventing nonfatal stroke but not other vascular events in patients with nonrheumatic AF.

Source of funding: North Thames Research and Development Programme.

For correspondence: Dr. F.C. Taylor, Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW England, UK. FAX 44-117-928-3581.


Table. Oral anticoagulation vs antiplatelet treatment for nonrheumatic atrial fibrillation (mean study follow-up for the 5 trials 12 to 42 mo)*

Outcomes Odds ratio (95% CI) RRR (CI) NNT (CI)
Nonfatal stroke 0.68 (0.46 to 0.99) 31% (1 to 53) 78 (46 to 2500)
All vascular events 0.79 (0.61 to 1.02) Not significant Not significant
Fatal stroke 0.74 (0.39 to 1.40) 26% (-39 to 61) Not significant
Fatal vascular events 0.86 (0.63 to 1.17) 13% (-16 to 35) Not significant
All-cause mortality 0.94 (0.72 to 1.21) 5% (-19 to 26) Not significant
RRI (CI) NNH
Major bleeding events 1.45 (0.93 to 2.27) 44% (-7% to 121) Not significant

*Abbreviations defined in Glossary; NNT and its CI calculated from data in article.


Commentary

Taylor and colleagues state that “we would strongly favour antiplatelet drugs in preference to long term anticoagulation.” This recommendation is in marked contrast to other publications that strongly recommend oral anticoagulation for patients with AF, especially those at high risk for stroke (the risk for stroke varies markedly among patients with AF) (1, 2). Why the difference?

Taylor and colleagues did not include a large randomized controlled trial of 455 high-risk patients that found a marked decrease in stroke when oral anticoagulation was compared with aspirin (hazard ratio 0.38, CI 0.23 to 0.64, P < 0.001) (3). Another randomized controlled trial not included compared adjusted-dose warfarin (INR 2.0 to 3.0) with aspirin plus fixed low-dose warfarin in high-risk patients and found a marked benefit of adjusted-dose warfarin (annual stroke rate 1.9% vs 7.9%) (4). Because the addition of low-dose warfarin to aspirin would, if anything, be more efficacious than aspirin alone, this study provides more evidence supporting the considerably greater efficacy of oral anticoagulation. Previous reviews focused on stroke prevention; Taylor and colleagues place more emphasis on a constellation of vascular events, including stroke, myocardial infarction, thromboembolism, and vascular death.

When all studies are considered, I believe that the evidence supporting the greater efficacy of oral anticoagulation over aspirin is compelling and that this benefit is clinically important, particularly in patients with AF who are at high risk for cardioembolic stroke (5). Aspirin is the preferred choice in patients with AF who are at low risk for stroke.

Andreas Laupacis, MD, MSc
Institute for Clinical Evaluative Sciences
Toronto, Ontario, Canada


References

1. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999;131:492-501. [PubMed ID: 10507957]

2. Albers GW, Dalen JE, Laupacis A, et al. Antithrombotic therapy in atrial fibrillation. Chest. 2001;119:194-206S. [PubMed ID: 111576493].

3. EAFT (European Atrial Fibrillation Trial) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet. 1993;342:1255-62. [PubMed ID: 7901582]

4. Stroke Prevention in Atrial Fibrillation Investigators. Adjusted dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Randomized Trial. Lancet. 1996;348:633-8. [PubMed ID: 8782752]

5. Hart RG, Halperin JL. Atrial fibrillation and stroke. Concepts and Controversies. Stroke. 2001;32:803-8.11239205


Authors' Response

Comparison of fatal events provides the most robust evidence of whether anticoagulation is better than aspirin because biased ascertainment is less likely. We feel that clinicians would be misguided to base treatment decisions on a marginally significant finding for nonfatal stroke.