Annals of Emergency Medicine
Volume 41, Issue 1 , Pages 141-143, January 2003

Anticoagulation or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter

Division of Emergency Medicine, University of Alberta, Edmonton, Alberta, Canada

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Abstract 

[Ann Emerg Med . 2003;41:141-143.]

 

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Systematic review source 

This is a systematic review abstract, a regular feature of the Annals ’ Evidence-Based Emergency Medicine (EBEM) series. Each features an abstract of a systematic review from the Cochrane Database of Systematic Reviews and a commentary by an emergency physician knowledgeable in the subject area.

The source for this systematic review abstract is: Seagal JB, McNamara RL, Miller MR, et al. Anticoagulation or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford, United Kingdom: Update Software; 2002.

The Annals ’ EBEM editors prepared the abstract of this Cochrane systematic review as well as the Evidence-Based Medicine Teaching Points.

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Objective 

To evaluate the efficacy and safety of anticoagulants and antiplatelet agents in the prevention of thromboembolic events and death in adults with nonpostoperative and nonrheumatic atrial fibrillation.

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Data sources 

The primary source was the Central database of the Cochrane Collaboration. A broad search of both MEDLINE, EMBASE, and the “related articles” feature of PubMed was conducted (until December 1999). The tables of contents of Annals of Internal Medicine, Archives of Internal Medicine, Circulation, and American Journal of Cardiology were also searched.

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Study selection 

Randomized controlled trials enrolling adults being managed for atrial fibrillation and/or flutter. Studies of postoperative patients and those with rheumatic valvular disease were excluded. Studies were included if they examined the use of anticoagulants or antiplatelet agents (eg, warfarin, acetylsalicylic acid, combination of low-dose warfarin and acetylsalicylic acid, low molecular weight heparin) for the prevention of stroke. The primary outcome was stroke; the secondary outcomes were major bleed (including cerebral hemorrhage) and death.

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Data extraction 

Two reviewers independently assessed studies for inclusion and quality. One reviewer abstracted quantitative data that were checked for accuracy by a second reviewer. The quality forms had 6 categories with 22 questions that were adopted from previous meta-analyses. Data were reported as odds ratios (ORs); a fixed-effects or random-effects model was used, based on the study's heterogeneity.

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Main results 

From a total of 39 abstracts, 14 articles were selected for inclusion in this review. The included studies involved several important different comparisons: (1) warfarin versus placebo; (2) acetylsalicylic acid versus placebo; and (3) warfarin versus acetylsalicylic acid. Warfarin was more effective than placebo for the prevention of primary stroke (OR 0.30; 95% confidence interval [CI] 0.19 to 0.48) without an increase in major bleeding (OR 1.90; 95% CI 0.89 to 4.04). Clinically, this translates into the prevention of 30 strokes at the expense of 6 additional major bleeds using warfarin, assuming a baseline stroke risk of 45 per 1,000. For primary prevention of stroke, acetylsalicylic acid produced no clear stroke reduction (OR 0.68; 95% CI 0.29 to 1.57) and no increase in major bleeding (OR 0.81; 95% CI 0.37 to 1.78). In comparing warfarin to aspirin, there were fewer strokes in patients treated with warfarin (OR 0.64; 95% CI 0.43 to 0.96) and no increase in major bleeding (OR 1.58; 95% CI 0.76 to 3.27). Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarin.

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Conclusions 

The authors of this review strongly support the use of warfarin in patients with atrial fibrillation who have an average or greater risk of stroke, unless there is a specific risk factor for hemorrhage. The risk of hemorrhage is outweighed by the prevention of stroke in most patients. Acetylsalicylic acid may be useful in preventing stroke in a subgroup of low-risk patients with less risk of hemorrhage than with warfarin.

Cochrane Systematic Review Author Contact 

Jodi B. Seagal, MD General Internal Medicine John Hopkins University Baltimore, MD E-mail jsegal@welch.jhu.edu

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Commentary: Clinical implication 

Atrial fibrillation is the most common serious chronic cardiac rhythm disturbance, with its prevalence doubling with each decade of age from 0.55% at age 50 to 59 to 9% at age 80 to 89 years.1 The incidence of acute atrial fibrillation also doubles with advancing age, independent of any changes in the prevalence of the predisposing conditions. The annual incidence in men increases from approximately 5 per 1,000 at age 50 to 54 to 45 per 1,000 at ages 85 to 94 years. In women, the incidence increases from 2.5 to 30 per 1,000 at these ages.1 The most important complication of atrial fibrillation is cerebral thromboembolism, increasing the risk of a stroke four- to fivefold. Approximately 15% of all ischemic strokes are attributable to atrial fibrillation, and at ages 80 to 89 years, approximately 24% of strokes are induced by atrial fibrillation. Survival is also seriously reduced, with mortality rates doubled across a wide age range.2 There is a consensus that addressing stroke prevention is of paramount importance in the treatment approach to acute and chronic atrial fibrillation.

Atrial fibrillation is also a common emergency department presenting problem. For example, patients present with acute atrial fibrillation and with complications directly related to atrial fibrillation (eg, transient ischemic attack, stroke, congestive heart failure, chest pain). Although most of our attention has been necessarily focused on the treatment of the acute arrhythmia, the selection of antiplatelet and anticoagulant therapy for these patients is an important prevention consideration, even in the ED. This systematic review consolidates a complex and confusing set of studies and provides sound evidence on which to base therapeutic decisions.

The review summarizes a number of comparisons, and space does not permit a full discussion of all of these. The main questions for emergency physicians will be reviewed: What is the evidence for and against warfarin therapy in atrial fibrillation and who should receive antiplatelet therapy? The summary analysis of warfarin versus placebo for stroke prevention clearly favors warfarin. Pooling of 5 studies in this subgroup analysis demonstrates an impressive reduction in stroke (OR 0.30), with only minor increased risk of bleeding; this translates into reducing the rate of thromboembolic event by 30 per 1,000 person-years at the expense of 6 major hemorrhages per 1,000 person-years. Most importantly, the elderly were not at an increased risk of intracranial hemorrhage (0.3% per year),3 and the risk factors associated with increased hemorrhage included male veterans, alcohol abusers, and those with chronic renal insufficiency or previous gastrointestinal bleed.4 For patients who are 65 years or younger without any cardiac risk factors (eg, hypertension, diabetes mellitus, congestive heart failure, prior transient ischemic attack/cerebrovascular accident, rheumatic heart disease), the rate of stroke is the same for warfarin and placebo; consequently, warfarin treatment is not indicated.3 Comparing warfarin with aspirin, there is a 26% reduction in thromboembolic event, with a trend for an increase in major bleeding that was not statistically significant. For the primary prevention of stroke, aspirin alone does not demonstrate a significant stroke reduction, although a trend in favor of acetylsalicylic acid does emerge. Clinically, aspirin would prevent 17 strokes without increasing major bleeding. Physicians need to carefully weigh the risks and benefits of anticoagulant therapy before initiating treatment.

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Take home message 

Warfarin should be considered for patients who are older than 65 years of age and present with chronic or recurrent atrial fibrillation. For patients without risk factors for bleeding, warfarin remains superior to acetylsalicylic acid or placebo for preventing thromboembolic phenomena. Acetylsalicylic acid alone shows a trend in decreasing the risk of thromboembolic phenomena; however, acetylsalicylic acid alone should be reserved for those who have an increased risk of bleeding (eg, alcoholics, renal insufficiency, previous gastrointestinal bleeding, those with high risks for falling) and patients with low risk of embolic event. Coordinated care between the ED and the primary care physician is an important consideration; efforts to improve this coordination need to be evaluated.

EBEM Commentator Contact 

Barry M. Diner, MD, MSc (Candidate) Division of Emergency Medicine University of Alberta Edmonton, Alberta, Canada E-mail dinerdoc@shaw.ca

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Evidence-based medicine teaching points 

QUOROM (Quality of Reporting of Meta-analyses) Statement.5 

In 1996, a large, international, multidisciplinary group of systematic review experts (eg, methodologists, editors, epidemiologists, statisticians) developed evidence-based guides designed to improve the quality of reports of meta-analyses of randomized controlled trials. The resultant guideline, called the QUOROM Statement, contains a checklist and flow diagram that meta-analysis authors and reviewers can follow. It provides readers with information about search strategies, selection criteria, validity assessment, data abstraction, study characteristics, quantitative data synthesis, and review flow. In essence, it is similar to the CONSORT (Consolidated Standards for Reporting of Trials) statement for randomized controlled trial reporting, but focuses on reports of meta-analyses. Many journals have supported the idea of standardized reporting of systematic reviews and have adopted the QUOROM statement. In fact, a randomized controlled trial is being conducted among these journals to determine whether using this guideline improves the quality of systematic review reporting.

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References 

  1. Kannel WB, Abbott RD, Savage DD, et al.  Coronary heart disease and atrial fibrillation: The Framingham Study. Am Heart J. 1983;106:389–396
  2. Kannel WB. Epidemiology of atrial fibrillation: Risk factors and hazards. Presented at: First Virtual Congress of Cardiology; October 1, 1999-March 31, 2000; Argentina.
  3. Atrial Fibrillation Investigators . Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med. 1994;154:1449–1457
  4. McMahan DA, Smith DM, Carey MA, et al.  Risk of major hemorrhage for outpatients treated with warfarin. J Intern Med. 1998;13:311–316
  5. Moher D, Cook DJ, Eastwood S, et al.  Improving the quality of reports of meta-analyses of randomised controlled trials: The QUOROM statement. Lancet. 1999;354:1896–1900

PII: S0196-0644(02)84964-2

doi:10.1067/mem.2003.41

Annals of Emergency Medicine
Volume 41, Issue 1 , Pages 141-143, January 2003

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