Home
Subject Index
Feedback
Health Evidence Bulletins - Wales

Coronoary Heart Disease

5: Atrial Fibrillation

Standard 5:

Everyone diagnosed with Atrial Fibrillation should be offered appropriate evidence based care.

Literature search:  Comprehensive systematic search to July 2002 plus selected update searches to December 2003 as advised by review groups

National Service Framework
i.  National Assembly for Wales.  Tackling coronary heart disease in
Wales: implementing through evidence.  Cardiff: National Assembly for Wales, July 2001

AF affects about 5% of the UK population over 65 years of age, with a prevalence rising to 10% in those over the age of 75.

What is the latest prevalence information for Wales/the UK?

5.1  Prevalence of atrial fibrillation
The Statements   The Evidence
5.1a.  The number of patients in the England and Wales with identified atrial fibrillation is increasing. The prevalence of atrial fibrillation in 1998 was 12.1/1,000 in men and 12.7/1,000 in women. Prevalence increased from less than 1/1,000 in under 35 year olds to over 100/1000 in those aged 85 years and over. There was a 22% increase in the age standardised prevalence of atrial fibrillation in men and a 14% increase in women between 1994 and 1998.  Applying the age and sex specific prevalence and treatment rates to the population gives an estimate of around 650,000 cases of atrial fibrillation in England and Wales. The greatest number of cases occurs in the 75-84 year old age groupi.

No data are available for Wales aloneii.

i.  Majeed A, Moser K, Carroll K. Trends in the prevalence and management of atrial fibrillation in general practice in England and Wales, 1994-1998: analysis of data from the general practice research database. Heart 2001; 86(3):284-288.
(Type IV evidence – retrospective longitudinal analysis of data from the general practice research database in England and Wales - 1.4 million patients, of all ages, registered with 211 general practices)
ii.  Advice from
stats.healthinfo@wales.gsi.gov.uk

top

5.1b.  The population prevalence of atrial fibrillation (AF) in a large middle-aged Scottish cohort was 6.5 cases/1,000 examinations. Prevalence was higher in men and older subjects.  The prevalence rates in subjects aged 50-59 years were 7.2/1,000 in men and 2.9/1,000 in women.  The male and female rates in those aged 60-69 years were 10.2 and 7.4/1,000 respectively.   In those who were re-screened, the four year incidence of AF was 0.54 cases/1,000 person years.   The rate of incident hospitalisation for AF was 1.9 cases/1,000 person yearsi. i.  Stewart S, Hart CL, Hole DJ, McMurray JJV. Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study. Heart 2001; 86(5):516-521.
(Type IV evidence – prevalence/incidence study in the Renfrew/Paisley population cohort of 15,406 men and women aged 45-64 years living in the west of Scotland. This cohort was initially screened between 1972 and 1976 and again between 1977 and 1979. Incident hospitalisations with AF in the 20 year period following initial screening were also studied)
5.1c.  In a Californian study of adults aged 20 years and over, the prevalence of atrial fibrillation was 0.95% (95% CI 0.94%-0.96%).  AF was more common in men than in women (1.1% vs 0.8%, p<0.001).  Prevalence increased from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older.  Among persons aged 50 years or older, prevalence of AF was higher in whites than in blacks (2.2% vs 1.5%, p<0.001)i. i.  Go AS, Hylek EM, Phillips KA et al.  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.  Journal of the American Medical Association  2001; 285(18): 2370-2375
http://www.jr2.ox.ac.uk/bandolier/band88/b88-6.html [accessed 22.12.03])
(Type IV evidence – cross-sectional study of 17,974 adults, aged 20+, enrolled in a large health maintenance organisation in California, who had atrial fibrillation diagnosed between July 1996 and December 1997.  Discussed in Bandolier  2001; 88(6)

top

National Service Framework Extractsi
i.  National Assembly for Wales. 
Tackling coronary heart disease in
Wales: implementing through evidence.  Cardiff: National Assembly for Wales, July 2001

The risk of stroke in patients with atrial fibrillation is about 5% per year and the stroke recurrence rate is 12% per year with an annual risk of death of 5%, depending on other risk factors and age.

What is the latest evidence on stroke risk for patients with atrial fibrillation?

5.2  Morbidity, mortality and stroke risk for patients with atrial fibrillation
The Statements   The Evidence
5.2a.  In subjects from the original cohort of the Framingham Heart Study, atrial fibrillation (AF) was associated with a 1.5- to 1.9-fold mortality risk after adjustment for the preexisting cardiovascular conditions with which AF was related. The decreased survival seen with AF was present in men and women and across a wide range of ages.  By pooled logistic regression, after adjustment for age, hypertension, smoking, diabetes, left ventricular hypertrophy, myocardial infarction, congestive heart failure, valvular heart disease, and stroke or transient ischemic attack, AF was associated with an odds ratio for death of 1.5 (95% CI, 1.2 -1.8) in men and 1.9 (95% CI, 1.5-2.2) in women. The risk of mortality conferred by AF did not significantly vary by age. However, there was a significant AF and sex interaction: AF diminished the female advantage in survivali. i.  Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998; 98(10):946-952.
(Type IV evidence – 40 year follow-up of the original Framingham Heart Study cohort. Of the original 5,209 subjects, 296 men and 325 women [range 55-94 years, mean ages, 74 and 76 years, respectively] developed atrial fibrillation and met eligibility criteria)
5.2b.  Atrial fibrillation is responsible for approximately one in seven strokes in patients of all ages and for one in four strokes in patients aged >80 years.  Although the average annual risk of stroke is approximately 5%, there is substantial risk heterogeneity within the population of patients with atrial fibrillation. Risk stratification on the basis of demographic, clinical, and echocardiographic features identifies populations with annual risk of stroke ranging from >7%, clearly warranting warfarin anticoagulation, to <1%, at which the risks and disutility of antithrombotic therapy offset its benefitsi.

See also section 5.5.

i.  Anderson DC, Koller RL, Asinger RW, Bundlie SR, Pearce LA. Atrial fibrillation and stroke: Epidemiology, pathophysiology, and management. Neurologist 1998; 4(5):235-258.
(Type V evidence – expert review)

top

5.2c.  A statistically significant multivariable adjusted hazard ratio for ischaemic stroke in a cohort of middle-aged men was 3.90 (95% CI, 2.01-7.58) for the presence of atrial fibrillationi.
Caveat: 
In this young population, at enrollment, only a very small number of participants had atrial fibrillation (0.85%, n=41).
i.  McCarron P, Greenwood R, Elwood P et al. The incidence and aetiology of stroke in the Caerphilly and Speedwell Collaborative Studies II: risk factors for ischaemic stroke. Public Health 2001; 115(1):12-20.
(Type IV evidence -  Data on risk factors collected through validated questionnaires and physical and clinical measurements from representative cohort of 4,861 middle aged men from South Wales and south-west England.  Average age at enrollment = 53.6 years.  Follow up 14-19 years (median 17 years))
5.2d.  In Scotland, the number of first-ever hospitalisations for atrial fibrillation increased two-fold between 1986 and 1995.  Although the age of patients has progressively increased during this period, short and medium case-fatality rates have declined, especially in men.  This may partly reflect better treatment.  However, changing admission thresholds and other factors could also have led to an apparent improvement in prognosis.  Nevertheless, medium-term case fatality remains substantial after a first ever admission to hospital with AF.  Short term (30 day) case-fatality fell from 4.0% to 3.1% in men (p<0.001) and 4.1% to 3.8% in women (p<0.01).  Medium term case-fatality (31-day to 2-year) fell from 25% to 22% in men and 27% to 25% in women (p for both <0.001)i. i.  Stewart S, MacIntyre K, Chalmers JWT et al.   Trends in case-fatality in 22,968 patients admitted for the first time with atrial fibrillation in Scotland, 1986-1995.  International Journal of Cardiology  2002; 82: 229-236
(Type IV evidence – retrospective calculation, using the Scottish Morbidity Record Scheme, of short (30-day) and medium (31 day to 2 years) case-fatality rates for all 22,968 patients admitted to Scottish hospitals for the first time with a principal diagnosis of atrial fibrillation between 1986 and 1995)

top

5.2e.  Atrial fibrillation (AF) is a significant independent predictor of fatal ischaemic stroke in people aged 60 and overi.

The relative risk of stroke in patients with atrial fibrillation was 3.18 (95% CI 2.62-3.85) for ischaemic stroke.  The higher prevalence of left ventricular hypertrophy in older persons with chronic atrial fibrillation contributes to the higher incidence of thromboembolic strokei.

i.  Aronow WS, Ahn C, Kronzon I, Gutstein H . Association of left ventricular hypertrophy and chronic atrial fibrillation with the incidence of new thromboembolic stroke in 2,384 older persons. American Journal of Cardiology 1999; 84(4):468-469.
(Type IV evidence – prospective study of 2,384 persons, mean age 81±9 years (range 60-103).  Mean follow-up, 44±21 months)

National Service Framework Extractsi
i.  National Assembly for Wales. 
Tackling coronary heart disease in
Wales: implementing through evidence.  Cardiff: National Assembly for Wales, July 2001

The optimum assessment of the patient presenting with atrial fibrillation includes a 12 lead ECG and an echocardiogram.

What are the best assessment procedures?

5.3  Screening and assessment of atrial fibrillation
The Statements   The Evidence
5.3a.  Guidelines are available which describe the minimum clinical evaluation criteria in patients with atrial fibrillationi. i.  Fuster V, Ryden LE, Asinger RW et al. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients with Atrial Fibrillation). European Heart Journal 2001; 22(20):1852-1923.
Executive summary available:  http://www.acc.org/clinical/guidelines/
atrial_fib/exec_summ/exec_afindex.htm 
[accessed 22.12.03]
(Evidence-based guidelines -  Authoritative consensus guidelines based on a systematic review of the literature, literature search to June 2000.  May lack multiprofessional and patient input)
Also published in:  Circulation 2001; 104(17):2118-2150, Journal of the American College of Cardiology 2001; 38(4):1266

top

5.3b.  A randomised controlled trial is in progress to examine targeted screening versus systematic population screening for atrial fibrillation in the over 65si.

i.  Randomised controlled trial and cost effectiveness study of targeted screening versus systematic population screening for atrial fibrillation in the over 65s: the SAFE study.  National Research Register 2002 Issue 1: N0484056617.  Lead researcher: University of Birmingham.  End date: 31.05.2003
(Ongoing trial: 24,000 patients aged over 65 from approximately 24 purposefully selected general practices from the West Midlands)

National Service Framework Extractsi
i.  National Assembly for Wales. 
Tackling coronary heart disease in
Wales: implementing through evidence.  Cardiff: National Assembly for Wales, July 2001

The treatment aims are achieving stable sinus rhythm (SR), or where this is not possible the prevention of embolic complications. This may require the use of potentially hazardous medicines and procedures.

Recent onset persistent atrial fibrillation requires immediate assessment and anticoagulation with heparin prior to attempts to restore normal rhythm, which may be either pharmacological or electrical (with the need for sedation or a brief general anaesthetic).

In persistent atrial fibrillation of less than 3 months duration, an attempt to restore normal rhythm by cardioversion (usually electrically) should be made with prior anticoagulation with warfarin for 4 weeks and consideration of medication to maintain normal rhythm.

The best current evidence concerning the electrical/pharmacological conversion of atrial fibrillation and the subsequent maintenance of sinus rhythm?

5.4  Cardioversion (electrical or pharmacological) and the maintenance of sinus rhythm
The Statements   The Evidence
Rate control versus rhythm control
5.4a.  Management of atrial fibrillation with the rhythm-control   strategy offers no survival advantage over the rate-control strategyi,ii,iii.

In the AFFIRM trial, mortality at five years for the rhythm- and rate-control groups was 23.8% and 21.3% respectively (Hazard ratio 1.15,  95% CI 0.99-1.34, p=0.08).  More patients in the rhythm-control group than in the rate control group were hospitalised, and there were more adverse drug effects in the rhythm-control group as well.  Anticoagulation should continue in this group of high-risk patients.  In both groups, the majority of strokes occurred after warfarin had been stoppedi.

In the RACE trial, after a mean of 2.3± 0.6 years, 39% of the 266 patients in the rhythm-control group had sinus rhythm, as compared with 10% of the 256 patients in the rate-control group. The primary end point of death from a variety of cardiovascular causes occurred in 44 patients (17.2%) in the rate-control group and in 60 (22.6%) in the rhythm-control groupii.
Caveat: 
Baseline characteristics were similar although more patients in the rhythm-control than the rate-control group had hypertension.

In the PIAF trial, with respect to self-reported symptomatic improvement of palpitations, dyspnoea and dizziness in patients with atrial fibrillation, the therapeutic strategies of rate versus rhythm control yielded similar clinical results overall.  However, exercise tolerance is better with rhythm control, although hospital admission is more frequent.  Over the observation period of one year, a similar proportion of patients reported improvement in symptoms in both groups (p=0.3).  Amiodarone administration resulted in pharmacological restoration of sinus rhythm in 23% of patients.  Walking distance in a 6 minutes walk test was better in the amiodarone compared to the diltiazem group, but assessement of quality of life showed no differences between groups.  The incidence of hospital admission was higher in the amiodarone group (69% vs 24%, p=0.001).  Adverse drug effects more frequently led to a change of therapy in the amiodarone group (25% vs 14%, p=0.036)i.
Caveats: 
There were some baseline differences between groups but no information was provided to say if these were statistically significant.  Physicians could make substantial changes to treatment within the study.  The trial was small with a large number of exclusion criteria.  There were no data on other important outcomes such as transient ischaemic attack and stroke.

i.  The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators.  A comparison of rate control and rhythm control in patients with atrial fibrillation.  New England Journal of Medicine  2002; 347(23): 1825-1833
(Type II evidence – randomised controlled trial of 4,060 patients (mean age 69.7±9.0 years) assigned to treatment with antiarrythmic drugs and/or cardioversion to maintain sinus rhythm or the use of rate-controlling drugs, allowing atrial fibrillation to persist. Mean follow up period = 3.5 years.  The antiarrhythmic drugs included amiodarone, disopyramide, flecainide, moricizine, procainamide, propafenone, quinidine, sotalol, dofetilide and combinations. The rate controlling drugs included beta-blockers, calcium-channel blockers (verapamil and diltiazem), digoxin and combinations)
ii.   Van Gelder IC, Hagens VE, Bosker HA et al; for the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group.  A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. 
New England Journal of Medicine.  2002; 347(23):1834-40
(Type II evidence – randomized controlled trial of 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aimed at rate control or rhythm control. 
Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication. Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs.  The end point was a composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, implantation of a pacemaker, and severe adverse effects of drugs)
iii.  Hohnloser SH, Kuck K-H, Lilienthal J; for the PIAF Investigators.  Rhythm or rate control in atrial fibrillation – Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial.  Lancet  2000; 356: 1789-1794
(Type II evidence – open label randomised trial of 252 patients comparing rate (diltiazem) with rhythm (amiodarone) control.  In the diltiazem group, no attempts were made to terminate atrial fibrillation.  If administration of diltiazem alone did not result in adequate rate control, additional therapy was left to the discretion of the treating physician. In the amiodarone group, patients underwent pharmacological and, if necessary, electrical cardioversion followed by antiarrhythmic therapy)

top

Electrical cardioversion – see also rate versus rhythm control (statement 5.4a)
5.4b.  When electrical cardioversion is carried out, the transesophageal echocardiography guided approach with short-term anticoagulation is considered to be a safe and clinically effective alternative to the conventional approach, and it is advocated in patients in whom earlier cardioversion would be clinically beneficiali. i.  Klein AL, Murray RD, Grimm RA. Role of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation. Journal of the American College of Cardiology 2001; 37(3):691-704
(Type V – expert review)
5.4c.  Patients with atrial fibrillation lasting more than 48 hours or of unknown duration should receive anticoagulation for at least 3 to 4 weeks before and after cardioversioni.

i.  Fuster V, Ryden LE, Asinger RW et al. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients with Atrial Fibrillation). European Heart Journal 2001; 22(20):1852-1923.
(Evidence-based guidelines -  Authoritative consensus guidelines based on a systematic review of the literature, literature search to June 2000.  May lack multiprofessional and patient input)
Also published in:  Circulation 2001; 104(17):2118-2150, Journal of the American College of Cardiology 2001; 38(4):1266
Executive summary available:  http://www.acc.org/clinical/guidelines/
atrial_fib/exec_summ/exec_afindex.htm 
[accessed 22.12.03]

5.4d.  In a multivariate analysis of clinical variables, independent predictors of unsuccessful electrical cardioversion  were a longer duration of AF (odds ratio per longer period of durations=1.64, p=0.0001) and a greater body weight (OR=1.14, p=0.01).  In a multivariable analysis of echocardiographic data, a lower ejection fraction was the only predictor of unsuccessful cardioversion (OR=1.15, p=0.04)i. i.  Elhendy A, Gentile F, Khandheria BK et al.  Predictors of unsuccessful electrical cardioversion in atrial fibrillation.  American Journal of Cardiology  2002; 89: 83-86
(Type IV evidence – case series of 692 patients (459 men (66%) and 233 women (34%), mean age±SD 67±13 years) with atrial fibrillation who had a first elective direct-current cardioversion at Mayo Clinic, Rochester US.  The duration of AF was ≥48 hours in 653 patients (94%) and <48 hours in 39 patients (6%))

top

5.4e.  A trial is ongoing to compare the safety and efficacy of subcutaneous enoxaparin with intravenous heparin/oral phenprocoumon before and after cardioversion (stratified to with or without exclusion of left atrial thrombi by transesophageal echocardiography)i. i.  Stellbrink C, Hanrath P, Nixdorff U et al; on behalf of the ACE Study Group.  Low molecular weight heparin for prevention of thromboembolic complications in cardioversion – rational and design of the ACE study (Anticoagulation in Cardioversion using Enoxaparin).  Z Cardiol.  2002; 91: 249-254
(Type II evidence – ongoing multicentre randomized controlled trial of 500 patients)
Pharmacological cardioversion – see also rate versus rhythm control (statement 5.4a)

5.4f.  Amiodarone is effective for converting atrial fibrillation to sinus rhythm in a wide range of patientsi,ii. Although use of amiodarone is apparently safe, safety data are too scarce for definitive conclusionsi.

The relative risk (RR) for achieving sinus rhythm within a four-week period was 4.33 (95% confidence interval [CI], 2.76-6.77) for trials with mean AF duration of greater than 48 hours and 1.40 (95% CI, 1.25-1.57) for those with AF of 48 hours or less. The risk differences for these two groups were 27% and 26%, respectively, yielding a number needed to treat of four for both groups. The low control event rate among trials with long duration of AF, compared with that of trials with a duration of 48 hours or less, explained the difference in the RR for conversion. Serious adverse events were infrequenti.

i.  Letelier LM.  Udol K.  Ena J.  Weaver B.  Guyatt GH.  Effectiveness of amiodarone for conversion of atrial fibrillation to sinus rhythm: A meta-analysis.  Archives of Internal Medicine. 2003; 163(7): 777-785
(Type I evidence – systematic review, literature search to February 2001 with details of search and appraisal methods; 21 trials and 1,930 patients)

ii.  Hilleman DE, Spinler SA. 
Conversion of recent-onset atrial fibrillation with intravenous amiodarone:  A meta-analysis of randomized controlled trials.  Pharmacotherapy  2002; 22(1): 66-74
(Type I evidence – systematic review, literature search to March 2001of Medline and reference list follow-up only.  18 randomised controlled trials were included and 1,203 patients.)
Caveats:  Data from this review have not been included.  No unpublished trials were sought and publication bias could be an issue.  It is unclear whether any critical appraisal of the included trials was carried out, nor if there was testing for heterogeneity.  A simple “pooled estimate” was used for the meta-analysis.

top

5.4g.  Two older systematic reviews have compared agents for pharmacological cardioversioni,ii.

Conclusions from the first review were that, in recent onset atrial fibrillation of less than seven days, intravenous (IV) procainamide, high dose IV or high-dose combination IV and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to normal sinus rhythmi.

In recent onset AF of less than 90 days, IV ibutilide is more effective than placebo and IV procainamide.  In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapyi.

The authors concluded that for conversion of recent onset AF of less than seven days, procainamide may be considered a preferred IV agent and propafenone a preferred oral agent.  For conversion of recent-onset AF of longer duration (less than 90 days), IV ibutilide may be considered a preferred agenti

The second set of reviewers found that, although multiple antiarrhythmic agents had strong evidence of efficacy compared with control treatment for the maintenance of sinus rhythm, ibutilide/dofetilide and flecainide had particularly strong evidence of efficacy compared with control treatment for AF conversionii.

Compared with control treatment (placebo, verapamil, diltiazem, or digoxin), the odds ratio (OR) for conversion was greatest for ibutilide/dofetilide (OR=29.1; 95% confidence interval [CI], 9.8-86.1) and flecainide (OR=24.7; 95% CI 9.0-68.3). Less strong but conclusive evidence existed for propafenone (OR=4.6; 95% CI 2.6-8.2). Quinidine (OR=2.9; 95% CI 1.2-7.0) had moderate evidence of efficacy for conversion. Disopyramide (OR=7.0; 95% CI 0.3-153.0) and amiodarone (OR=5.7; 95% CI 1.0-33.4) had suggestive evidence of efficacy. Sotalol (OR=0.4; 95% CI 0.0-3.0) had suggestive evidence of negative efficacy. For MSR, strong evidence of efficacy existed for quinidine (OR=4.1; 95% CI 2.5-6.7), disopyramide (OR=3.4; CI 1.6-7.1), flecainide (OR=3.1; 95 % CI 1.5-6.2), propafenone (OR=3.7; 95% CI 2.4-5.7), and sotalol (OR=7.1; 95% CI 3.8-13.4). The only amiodarone data, from comparison with disopyramide, provided moderate evidence of efficacy for MSR. No trial evaluated procainamide. Direct agent comparisons and adverse event data were limitedii.
Caveat: 
Ibutilide and dofetilide are not available in the UK

i.  Slavik RS, Tisdale JE, Borzak S.  Pharmacologic conversion of atrial fibrillation:  A systematic review of available evidence.  Progress in Cardiovascular Diseases  2001; 44(2): 121-152
(Type I evidence – narrative systematic review, literature search to May 2001 (English language only), of 88 trials, 34 of which included a placebo group)
ii.  Miller MR, McNamara RL, Segal JB et al. Efficacy of agents for pharmacologic conversion of atrial fibrillation and subsequent maintenance of sinus rhythm: A meta-analysis of clinical trials. Journal of Family Practice 2000; 49(11):1033-1046.
(Type I evidence – systematic review, literature search to May 1998, of 36 randomised controlled trials (25 studied conversion to and 15 studied maintenance of sinus rhythm). The mean age range was 47 to 71 years, and seven trials studied patients with a mean age > 65 years. Follow-up duration for conversion studies was < 24 hours and for maintenance studies, one to 15 months.  Reviewed in: Many drugs are effective for conversion of AF and maintenance of sinus rhythm.  ACP Journal Club  2001; 135(1): 13)

 

 

 

 

 

 

 

 

 

 

 

top

5.4h.  A Cochrane review is in progress to investigate whether pharmacological cardioversion of atrial fibrillation/flutter reduces the annual risk of stroke, peripheral embolism and mortality.  The secondary aims are to evaluate whether pharmacological cardioversion reduces the rate of cognitive decline, improves the quality of life, reduces the use of anticoagulants, improves cardiac function and reduces the rates of re hospitalizationi.

i.  Cordina J, Mead G.  Pharmacological cardioversion for atrial fibrillation/flutter [Protocol].  In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.
(Systematic review in progress)

5.4i.  The addition of drugs to nonpharmacologic therapies can increase the effectiveness of these therapies for the conversion to, and maintenance of, sinus rhythm.  However, these hybrid therapies will remain the subject of conjecture in the absence of controlled clinical trials, which are urgently neededi. i.  Murgatroyd FD.  “Pills and pulses”: Hybrid therapy for atrial fibrillation.  Journal of Cardiovascular Electrophysiology 2002; 13: S40-S46
(Type V evidence – expert opinion & review of recent studies)
Cost-effectiveness studies in cardioversion and maintenance of sinus rhythm
5.4j.  A Markov decision analytic model suggests that cardioversion alone should be the initial management strategy for persistent nonvalvular atrial fibrillation.  On relapse of arrhythmia, repeated cardioversion plus low-dose amiodarone is cost-effective for patients at moderate to high risk for ischemic stroke.  For patients at high risk for ischemic stroke (5.3% per year), cardioversion alone followed by repeated cardioversion plus amiodarone therapy on relapse was most cost-effective ($9,300 per QALY in 1999) compared with cardioversion alone followed by warfarin therapy on relapse.  This strategy was also preferred for the moderate risk cohort (3.6% per year), but the benefit was more expensive ($18,900 per QALY).  In the lowest-risk cohort (1.6% per year), cardioversion alone followed by aspirin therapy on relapse was optimali.

For patients with nonvalvular atrial fibrillation, the two most effective and cost-effective strategies were cardioversion followed by long-term aspirin or warfarin if AF recurred and the same strategy with amiodarone addedii.
Caveat: 
This US study is based on effectiveness data from 1995.

Both the above studies were published before the rate control versus rhythm control trials.  See statement 5.4a.  Further cost-effectiveness analyses are required.

i.  Catherwood E, Fitzpatrick WD, Greenberg ML et al. Cost-effectiveness of cardioversion and antiarrhythmic therapy in nonvalvular atrial fibrillation.  Annals of Internal Medicine  1999; 130(8): 625-36
(Type IV evidence – Markov decision analytic model to compare the cost-effectiveness of cardioversion, with or without antiarrhythmic agents, with that of rate control plus warfarin or aspirin for a hypothetical cohort of 70-year old patients with different baseline risks for stroke)

ii.
  Eckman MH, Falk RH, Pauker SG.  Cost-effectiveness of therapies for patients with nonvalvular atrial fibrillation.  Archives of Internal Medicine 1998; 158: 1669-1677
 (Type IV evidence – cost-effectiveness analysis with a Markov state-transition model.  Reviewed in:  Cardioversion followed by aspirin alone or with amiodarone was cost-effective for nonvalvular atrial fibrillation. ACP Journal Club 1999; 130: 24)

top

National Service Framework Extractsi
i.  National Assembly for Wales. 
Tackling coronary heart disease in
Wales: implementing through evidence.  Cardiff: National Assembly for Wales, July 2001

The optimal management of atrial fibrillation is complex and requires close collaboration between the primary and secondary health care team.

The embolic risk in people with atrial fibrillation is variable, related mainly to their underlying cardiac condition, as is the potential for complications with anticoagulation. (Complications may vary due to “non cardiac” factors.) Thus individualised decisions need to be made on the relative risks and benefits – there are validated stratification protocols available.

Which validated risk stratification protocols assess embolic risk? 

What are the recommendations for anticoagulation management?

What are the recommendations for service provision (primary/secondary care)?

All patients with AF must have their need for long term anticoagulation assessed using nationally agreed and validated risk stratification/ assessment of any contraindications and this must be done in a way which explains to them the process and the recommended treatment. The anticoagulation programme must be quality assured and audited.

What is the evidence concerning risk stratification/assessment?  Best methods of quality assurance and audit?

top

5.5  The stratification of embolic risk in patients with atrial fibrillation and appropriate management strategies
The Statements   The Evidence
Embolic risk assessment in atrial fibrillation
5.5a.  When tested in a large cohort of patients with atrial fibrillation who were treated with aspirin, available risk-stratification schemes successfully identified patients with low rates of ischemic stroke, but less consistently identified high-risk patientsi.

Each of the three schemes predicted stroke and disabling stroke, and successfully identified patients at low risk (observed stroke rates of 0.3 to 1.1 per 100 person-years), although the fractions of the cohort that were categorized as low risk varied from 14% to 45%. The observed rates of ischemic stroke among patients categorized as high risk ranged from 3.5 to 7.2 per 100 person-years among the stratification schemes. Two schemes considered all patients >75 years old as high risk (observed stroke rate 4.2 per 100 person-years), while the remaining scheme classified one third of patients in this age group as low risk (observed stroke rate 0.6 per 100 person-years)i.

In a study of two of these stroke-risk stratification schemes the difference in stroke risk between those categorized as high versus moderate risk by the AFI/ACCP criteria was small.  Those classified as high risk by the SPAF III criteria were at higher risk than those classified as low or moderate risk (1.75% [95% CI 0.9-3.3] versus 3.7% [95% CI 2.1-5.8] per yearii.

Many people with AF in this population-derived cohort had relatively low rates of strokeii. Further studies to reliably stratify stroke risk in patients with AF are neededii.

A summary of risk stratification schemes is availableiii.

i.  Pearce LA, Hart RG, Halperin JL. Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation. American Journal of Medicine 2000; 109(1):45-51.
(Type IV evidence – criteria from three schemes of risk stratification were applied to a longitudinally observed cohort of 1,073 patients with atrial fibrillation who did not have prior cerebral ischemia and who were treated with aspirin alone or aspirin combined with low, ineffective doses of warfarin in a multicenter clinical trial (SPAF III).  The three schemes tested were the Atrial Fibrillation Investigators 1994, The American College of Chest Physicians Consensus 1998 and the Stroke Prevention in Atrial Fibrillation I & II 1995 studies)
ii.  Feinberg WM, Kronmal RA, Newman AB et al. Stroke risk in an elderly population with atrial fibrillation. Journal of General Internal Medicine 1999; 14(1):56-59.
(Type IV evidence – study of the stroke rate and predictive value of two published schemes for stroke risk stratification (SPAF II and the Atrial Fibrillation Investigators) in a population-derived cohort of 259 elderly people (> 65 years, mean age 74±6) with nonvalvular AF followed for a median of 5.3 years.  Follow-up was >99%)
iii.  Kamath S, Lip GYH. Risk stratification for thromboprophylaxis in atrial fibrillation. Cardiac Electrophysiology Review 2001; 5(2-3):171-176.

(Type V evidence – review of the three schemes included above and Lip Lancet 1999)

 

 

top

5.5b.  Another risk classification scheme (CHADS2) based on the AFI and SPAF III schemes has recently been published that provides a simple clinical way to estimate the risk of stroke in patients with non-rheumatic atrial fibrillation and, thus, assist treatment decisionsi.

The CHADSindex was the most accurate predictor of stroke (c statistic, which estimates the probability of concordance between predicted and observed responses, = 0.82, 95% CI 0.80-0.84) for patients who did, and did not, receive aspirin.  The stroke rate per 100 years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-3.7) for each one-point increase in the CHADSscore.  Aspirin was associated with a hazard rate of 0.80 (95% CI, 0.5-1.3), corresponding to a non-significant 20% relative risk reduction in the risk of strokei.

i.  Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ.  Validation of clinical classification schemes for predicting stroke.  Results from the National Registry of Atrial Fibrillation.  Journal of the American Medical Association  2001; 285 (22): 2864-2870
(Type IV evidence – validation of stroke risk classification schemes in 1,733 Medicare beneficiaries aged 65-95 years who had non rheumatic atrial fibrillation and were not prescribed warfarin at hospital discharge.  Follow up = 365-1,000 days [mean (median) 1.2 (1.0) years])
 

 

Therapy to reduce embolic risk in patients with atrial fibrillation

5.5c.   Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with non-valvular chronic or paroxysmal atrial fibrillation but modestly increases the absolute risk of major bleeding.  The balance of benefits and risks varies by patient subgroupi.  Treating 1,000 patients for one year with oral anticoagulants rather than aspirin would prevent 23 ischaemic strokes while causing nine additional major bleeding episodesi

Results from an older review suggested that, for primary prevention, assuming a baseline risk of 45 strokes per 1,000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was moderate evidence for fewer strokes among patients on warfarin than on aspirin [aggregate OR=0.64 [95% CI 0.43-0.96]], with only suggestive evidence for more major hemorrhage [OR =1.58 [95% CI 0.76-3.27]]. However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared to aspirin was low (5.5 per 1,000 person-years) compared to an older group (15 per 1,000 person-years). Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarinii.

i.  van Walraven C, Hart RG, Singer DE et al.  Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation.  An individual patient meta-analysis.  Journal of the American Medical Association 2002; 288: 2441-2448
(Type II evidence  - pooled analysis of patient-level data from AFASAK I & II, PATAF, EAFT, SPAF 1,/2 and 3;  4,052 patients in all)
Reviewed in:  Anonymous.  Aspirin or anticoagulant in nonvalvular AF.  Commentary in Bandolier  February 2003 108-5.

http://www.jr2.ox.ac.uk/bandolier/band108/b108-5.html 
[accessed 22.12.03]
(Type V evidence – expert commentary on the above review)
ii.  Segal JB, McNamara RL, Miller MR et al. Anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter. (Cochrane Review). In: The Cochrane Library, Issue 1 2003. Oxford: Update Software. (Most recent update 29 November 2000)
http://www.update-software.com/abstracts/ab001938.htm
[accessed 22.12.03]

(Type I evidence – systematic review, literature search to December 1999, of 14 randomised controlled trials.  Reviewed in:  Warfarin prevents stroke in nonrheumatic atrial fibrillation but has a higher risk for hemorrhage than other agents. ACP Journal Club 2001; 135(2): 59)

top

5.5d.  Cochrane reviews are also available that examine, independently, the efficacy of antiplatelet therapyi and oral anticoagulantsii for preventing stroke in patients with atrial fibrillation.
Caveat: 
Neither review has been updated since 1999
i.  Benavente O, Hart R, Koudstaal P, Laupacis A, McBride R.  Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. (Cochrane Review). In: The Cochrane Library, Issue 1 2003. Oxford: Update Software. (Most recent update 31 August 1999)
 
http://www.update-software.com/abstracts/AB001925.htm
[accessed 22.12.03]
(Type I evidence – systematic review and meta-analysis of two trials, 1,680 participants)
ii.  Benavente O, Hart R, Koudstaal P, Laupacis A, McBride R.  Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.
(Cochrane Review). In: The Cochrane Library, Issue 1 2003. Oxford: Update Software. (Most recent update 28 August 1999)

http://www.update-software.com/abstracts/ab001927.htm
[accessed 22.12.03]
(Type I evidence – systematic review and meta-analysis of five trials and 2,313 participants.  Limitations of the trials included relatively short follow-up and imprecise estimates for bleeding risks from selected participants)
5.5e.  A randomised controlled trial is underway to investigate whether patients aged 75 or over with non-rheumatic atrial fibrillation identified in general practice should be treated with aspirin or warfarini.

A smaller study is also underway to determine whether aspirin or warfarin is better in the prevention of strokes in patients aged 80-89 with persistent or permanent atrial fibrillationii.

i.  BAFTA – Birmingham Atrial Fibrillation Treatment of the Aged Study. A randomized controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly (aged > 75) primary care population. National Research Register 2002 Issue 1 Reference Number: N0138055882.  Lead Centre: University of Birmingham.  End date: 28.02.2005.
(Ongoing trial:  1,240 patients from 100-150 practices in the West Midlands)
ii.  A comparison of warfarin and aspirin for stroke prevention in octogenarians in atrial fibrillation study.  National Research Register 2002 Issue 1 Reference Number: N0164097348.  Centre:  Royal Hallamshire Hospital NHS Trust.  End date: 24.04.2003
(Ongoing trial: 200 patients)
5.5f.  A meta-analysis of six randomised controlled trials suggests that aspirin when added to oral anticoagulants (vitamin K antagonists) may increase the risk of intracranial hemorrhage, but the observation requires confirmation. The magnitude of the effect is uncertain, and the clinical importance is likely to be different for different patient populations. Use of aspirin with oral anticoagulants was associated with more than double the frequency of intracranial hemorrhage (relative risk = 2.4, 95% CI = 1.2-4.8, p = 0.02)i. i.  Hart RG. Benavente O. Pearce LA. Increased risk of intracranial hemorrhage when aspirin is combined with warfarin: A meta-analysis and hypothesis.  Cerebrovascular Diseases 1999; 9(4): 215-7
(Type I evidence – systematic review and meta-analysis of six randomised controlled trials in which aspirin was added to oral anticoagulants. Literature search to 1997, 3/6 trials did not report method of randomisation)

top

5.5g.  Patients with atrial fibrillation who have relatively low rates of ischaemic stroke, particularly disabling stroke, during treatment with aspirin can be readily identified.  The rate of primary events (stroke, systemic emboli, or transient ischemic attack) was 2.2% per year (95% CI 1.6%-3.0%), of ischemic stroke was 2.0% per year (95% CI 1.5%-2.8%), and of disabling ischemic strokes was 0.8% per year (95% CI, 0.5%-1.3%).  Those with a history of hypertension had a higher rate of primary events (3.6% per year) than those with no history of hypertension (1.1% per year) (p<0.001).  The rate of disabling ischemic stroke was low in those with and without a history of hypertension (1.4% per year and 0.5% per year, respectively).  The rate of major bleeding during aspirin therapy was 0.5% per yeari i.  The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. Patients with non-valvular atrial fibrillation at low risk of stroke during treatment with aspirin:.  Stroke Prevention in Atrial Fibrillation III Study.  Journal of the American Medical Association 1998; 279(16): 1273-1277
(Type IV evidence – prospective cohort study (mean duration of follow-up 2.0 years) of 892 participants with atrial fibrillation of mean (SD) age 67 (10) years, 78% men.  100% completed follow-up.  Patients were categorized as low risk based on the absence of four prespecified thromboembolic risk factors; recent congestive heart failure or left ventricular fractional shortening of 25% or less, previous thromboembolism, systolic blood pressure greater than 160 mm Hg, or female sex at age older than 75 years.  All participants were given aspirin, 325 mg/day)
5.5h.  Antiplatelet therapy protects against vascular events (if oral anticoagulants are unsuitable) among patients with atrial fibrillation.  Overall there was a proportional reduction of 24% (standard error of mean, 9%) in serious vascular events (or 23% (10%) if one small trial of indobufen versus placebo that also included some patients without atrial fibrillation is excluded).  The available evidence supports a daily dose of aspirin in the range of 75-150 mgi. i.  Antithrombotic Trialists’ Collaboration.  Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.  British Medical Journal  2002; 324(7329): 71-86
http://bmj.bmjjournals.com/
cgi/content/full/324/7329/71
[accessed 22.12.03]
(Type I evidence – systematic review, literature search to September 1997, of four trials including 2,770 patients with atrial fibrillation)

top

5.5i.  A nurse-led clinic in the primary-care setting that included on-site blood tests and a computer decision-support program for patients who were receiving warfarin was at least as effective as a hospital-based clinic. Data on proportion of time spent in the international normalized ratio range showed significant improvement for patients in the intervention group (p=0.008).  The groups did not differ for the proportion of tests in therapeutic range (although both groups improved from baseline levels), all-cause mortality (3 deaths in each group), serious adverse events (3 in each group), or overall adverse eventsi

The costs, per patient per year, in primary care versus hospital care were £170 (95% CI £149-190) versus £69 (£57-81).  Sensitivity analysis demonstrated that the cost in primary care could be reduced to under £100 per patient per year under plausible changes in the variablesii

i.  Fitzmaurice DA, Hobbs FD, Murray ET et al.  Oral anticoagulation management in primary care with the use of computerized decision support and near-patient testing.  A randomized, controlled trial.  Archives of Internal Medicine  2000; 160: 2343-2348
(Type II evidence – Randomised controlled trial, stratified by practice size, with one year follow-up in 12 of 21 potential general practices and 3 hospital clinics in Birmingham, England. Patients: 367 patients were recruited.  122 patients were allocated to nurse-led management in a primary care setting. The nurse met with the patient, measured the INR with on-site equipment, and used the computer program (Anticoagulation Management Support System) to direct dosing decisions.  There were also 102 intrapractice- and 143 interpractice-control patients. Reviewed in: A nurse-led clinic and computer decision-support software for anticoagulation decisions were as effective as a hospital clinic. ACP Journal Club 2001; 134(2):73.)
ii.  Parry D, Fitzmaurice D, Raftery J.  Anticoagulation management in primary care: a trial based economic evaluation.  British Journal of Haematology  2000; 111(2): 530-533
(Type IV evidence – economic evaluation using data from the above trial.  Costs were assessed at 1996-1997 prices.  Costs to the NHS but not to the patient and their family were considered)
5.5j.  In the context of shared decision making, individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation.  Among 97 patients aged 70-85, decision analysis indicated that 59 (61%, 95% CI 50%-71%) would prefer anticoagulation treatment – considerably fewer than those who would be recommended treatment according to guidelines.  There was marked disagreement between the decision analysis and guideline recommendations (kappa=0.25 or less).  Of 38 patients whose decision analysis indicated that they preferred not to be treated with warfarin, 17 (45%) were being prescribed warfarin; on the other hand, 28 (47%) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to bei.

Guidelines for the management of atrial fibrillation should be modified to incorporate patient-preferences in treatment decisions.  Decision analysis as a shared decision making tool, and in particular its impact on patients’ knowledge, satisfaction, and uptake of and adherence to medication, should be evaluated in a randomised controlled triali.

It is feasible to develop a decision analysis based computer software package that is acceptable to elderly patients and clinicians, and sensitive to patient preferences, but it requires time and expertise to use.  It is most likely that a tool of this type will best be used by a small number of clinicians who have developed experience of its use and can maintain their skills.  Further research is plannedii.

i.  Protheroe J, Fahey T, Montgomery AA, Peters TJ.  The impact of patients’ preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis.  British Medical Journal  2000; 320: 1380-1384
http://bmj.bmjjournals.com/cgi/
content/full/320/7246/1380
[accessed 22.12.03]
(Type IV evidence – observational study based on interviews of 260 randomly selected patients aged 70-85 years with atrial fibrillation, from eight general practices in Avon.  Of 196 eligible patients, 97 participated in decision making using decision analysis)
ii.  Thomson R, Robinson A, Greenaway J, Lowe P; on behalf of the DARTS team.  Development and description of a decision analysis based decision support tool for stroke prevention in atrial fibrillation.  Quality & Safety in  Health Care  2002; 11: 25-31
(Type IV – iterative development study of a computerized decision support tool)

top

5.5k.  A Markov decision analysis of long-term warfarin therapy assessed the contraindication of an increased risk of upper gastrointestinal tract bleeding to help delineate the magnitude of risk necessary to consider alternatives to warfarin therapy.  For 65 year old patients with average risks of stroke and upper GI tract bleeding, warfarin therapy was associated with 12.1QALYs per patient; aspirin therapy with 10.8 QALYs and no antithrombotic therapy with 10.1 QALYs.  For persons with significantly higher risks of upper GI tract bleeding and/or lower risks of stroke, warfarin was no longer clearly the optimal antithrombotic therapy (eg for 80-year-old persons with a baseline risk of stroke of 4.3% per year who were concurrently taking a conventional nonsteroidal anti-inflammatory drug; warfarin, 7.44 QALYs; aspirin, 7.39 QALYs; no treatment, 7.21 QALYsi. i.  Man-Son-Hing M, Laupacis A.  Balancing the risks for stroke and upper gastrointestinal tract bleeding in older patients with atrial fibrillation.  Archives of Internal Medicine  2002; 162: 541-550
(Type V evidence – expert opinion based on a Markov decision analysis, using data from a systematic literature search to December 2000)

 

5.5l.  An ongoing open, randomized, multicenter study is investigating the benefits and economic efficiency of self-management of oral anticoagulation in patients with atrial fibrillation (SMAAF study) in comparison with a group of patients given conventional care by a general practitioner or specialist.  The numbers of thromboembolic and hemorrhagic complications requiring treatment during the two-year follow-up period will be recorded as the primary end pointi. i.  Völler H, Glatz J, Taborski U et al. [Background and evaluation plan of a study on self-management of anticoagulation in patients with non-valvular atrial fibrillation (SMAAF Study)]. [German]. Z Kardiol 2000; 89(4):284-288
(Ongoing study of two thousand patients suitable for self-management assigned at random to either the self-management group or the control group – 2 year follow-up period)

top

5.5m.  Publication is awaited of the SPORTIF III and V Studies to determine the safety and efficacy of the oral direct thrombin inhibitor ximelagatran as an alternative to warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation i.

A NICE appraisal of ximelagatran for stroke prevention in patients with stroke and other thromboembolic complications associated with atrial fibrillation is expected in February 2006ii.

i.  Halperin JL.  Executive Steering Committee, SPORTIF III and V Study Investigators.  Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: Rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V).  American Heart Journal  2003; 146(3): 431-8
(Ongoing randomised controlled trials)
ii.  National Institute for Clinical Excellence.  Stroke prevention: 
Ximelagatran for stroke prevention in patients with stroke and other thromboembolic complications associated with atrial fibrillation.  NICE Technology Appraisal
http://www.nice.org.uk/cat.asp?c=98352
[accessed 15.01.04]
(Pending technology appraisal.  Final scope will be published September 2004)

5.5n.  In a cohort of atrial fibrillation patients given aspirin, those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors.  Patients with intermittent AF were, on average, younger (66 vs. 70 years, p < 0.001), were more often women (37% vs. 26% p < 0.001) and less often had heart failure (11% vs. 21%, p < 0.001) than those with sustained AF. The annualized rate of ischaemic stroke was similar for those with intermittent (3.2%) and sustained AF (3.3%)i. In patients with intermittent AF, independent predictors of ischaemic stroke were advancing age (relative risk [RR] = 2.1 per decade, p < 0.001), hypertension (RR = 3.4, p = 0.003) and prior stroke (RR = 4.1, p = 0.01). Of those with intermittent AF predicted to be high risk (24%), the observed stroke rate was 7.8% per year (95% CI 4.5-14).  Young patients with lone AF and those with a single documented episode were not included in this trial, which may explain the different results to other studies that suggest intermittent AF carries less stroke risk than sustained AFi.
Caveat: 
No data were available on the frequency or duration of intermittent AF factors which were likely to influence the risk of stroke.  Further studies are required.
i.  Hart RG, Pearce LA, Rothbart RM, McAnulty JH, Asinger RW, Halperin JL; for the Stroke Prevention in Atrial Fibrillation Investigators. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Journal of the American College of Cardiology 2000; 35(1): 183-187.
(Type IV evidence – longitudinal cohort study comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years. Independent risk factors for ischemic stroke were identified by multivariate analysis.  Study also discussed in: Pearce LA, Hart RG. Does pattern of atrial fibrillation affect stroke risk? Cardiology Review 2000; 17(7):13-15)

top

5.5o.  A study carried out in Avon in 1997 found that general practitioners appreciated the importance of antithrombotic therapy in patients who have suffered stroke, but take poor account of increasing age and other independent risk factorsi. i.  Fahey T, Rimmer J, Godfrey P. Risk stratification in the management of atrial fibrillation in the community.  British Journal of General Practice 1999; 49(441): 295-296.
(Type IV evidence – cross-sectional study of 750 patients identified from 14 practices by means of diagnostic READ codes or repeat prescriptions for digoxin from practice computers)
Cost-effectiveness of anticoagulation management decisions
The Statements   The Evidence
5.5p.  On the basis of a decision analysis, for most risk combinations warfarin treatment would have decreased health-care costs and increased quality-of-life years, although the clinical decision was sensitive to patients’ preferences and to the estimate of warfarin’s effectiveness. 97% of women with atrial fibrillation older than 75 years, and 69% aged 65-74 would have been recommended for treatment; for men, the corresponding figures would have been 75% and 53%. Using the upper quartile for the loss of quality of life associated with being on warfarin treatment, the model suggests all but two of the 116 patients without contraindications should be treated, whereas with the lower quartile, only 27 of 116 should be treatedi. i.  Thomson R, Parkin D, Eccles M, Sudlow M, Robinson A. Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Lancet 2000; 355(9208):956-962.
(Type IV evidence – Markov decision analysis to model decision-making with regard to warfarin treatment in patients with atrial fibrillation.  The decision analysis involved a systematic literature review supplemented by patients’ estimates of the quality of life associated with different states of health, secondary analysis of stroke-registry data, and estimation of service costs; it also incorporated a sensitivity analysis)

top

Ethnic differences
5.5q.  In one small UK study, 64% of Indo-Asians, 44% of Afro-Caribbeans and 11% of whites were unaware of their diagnosis of atrial fibrillation. Only 45% of the Group believed that there was some risk associated with warfarin therapy in the form of either “bleeding” or “poisoning”.  Only a minority of the Indo-Asians and Afro-Caribbeans studied felt that their doctor had given them enough information about their warfarin therapy and many from these ethnic groups felt that they were careless about taking their warfarini. i.  Lip GYH, Kamath S, Jafri M, Mohammed A, Bareford D.  Ethnic differences in patient perceptions of atrial fibrillation and anticoagulation therapy.  The West Birmingham Atrial Fibrillation Project.  Stroke  2002; 33: 238-244
(Type IV evidence – cross-sectional survey of 119 patients attending the anticoagulation clinic of a city center teaching hospital.  77 were male; mean age 69±9 years; of these, 39 were Indo-Asian (33%), 27 Afro-Caribbean (23%) and 53 white (44%).  The median duration of atrial fibrillation was 48 months.  The median duration of anticoagulation was 36 months (interquartile range, 12-84 months))
5.5r.  One chart review study suggest that elderly Hispanics exhibit the same increased sensitivity to warfarin as non-Hispanicsi.
Caveats: 
Patients were considered to be of Spanish origin if they had a Spanish surname (but only 54% of patients were male and 10% of the Group were not considered to be Hispanic).  The potentially interacting factors of diet and weight were not considered.
i.  Casner PR, Sandoval E.  Increased sensitivity to warfarin in elderly Hispanics.  Journal of Clinical Pharmacology  2002; 42: 145-150
(Type IV evidence – retrospective chart review of 243 patients (90% Hispanic))

National Service Framework Extractsi
i.  National Assembly for Wales. 
Tackling coronary heart disease in
Wales: implementing through evidence.  Cardiff: National Assembly for Wales, July 2001

… there should be an agreed patient pathway between LHG and the DGH for the care of those with atrial fibrillation based on the model pathway.

Which model pathways for atrial fibrillation exist?  Validation/comparisons?

No published examples found from the literature search carried out during the preparation of this Bulletin. 
(Most recent search – September 2003)

top

5.6  Surgical interventions
5.6a.  The traditional surgical treatment of atrial fibrillation is the Cox-Maze III procedurei,ii,iii.  The procedure, performed as open heart surgery, has a high success rate for sustaining normal heart rhythms, usually without the need for a pacemaker; however, it is the treatment of last resort for patients with atrial fibrillation who are unresponsive to medication therapy, electrical cardioversion, surgical ablation or pacemaker implantationi.

Contemporary and emerging surgical processes which have been developed as alternatives or adjuncts to the traditional Maze procedure include alternate energy sources (radiofrequency, microwave, cryothermy/cryoablation) and simplified left atrial lesion setsii,iii. These operations cure AF in 70% to 80% of patientsiiLaser technology is still in an experimental phase, and the clinical results are forthcomingiii.

i.  Green B.  The Maze III surgical procedure.  AORN Journal  2002; 76(1): 134-146
(Type V evidence – expert review)  
ii.  Gillinov AM.  Blackstone EH.  McCarthy PM.  Atrial fibrillation: current surgical options and their assessment.  Annals of Thoracic Surgery 2002; 74(6): 2210-2217
(Type V evidence – expert review) 

iii.  Viola N. 
Williams MR.  Oz MC.  Ad N.  The technology in use for the surgical ablation of atrial fibrillation.  Seminars in Thoracic & Cardiovascular Surgery  2002; 14(3):198-205
(Type V evidence – expert review) 
5.6b.  The authors of a systematic review concluded that ablation and pacing therapy is beneficial for highly symptomatic medically refractive atrial tachyarrhythmiasi.
Caveat: 
The reviewers for the Database of Abstracts of Reviews of Effectiveness (DARE) note a number of concerns about the quality of this review and do not support the authors’ conclusion.  The reviewers feel that from the strength of the evidence presented there is an overwhelming need to carry out appropriately designed randomised controlled trials to assess the effectiveness of this intervention in all patients regardless of symptoms.
i.  Wood MA, Brown-Mahoney C, Kay GN, Ellenbogen KA.  Clinical outcomes after ablation and pacing therapy for atrial fibrillation: a meta-analysis.  Circulation 2000; 101(10): 1138-1144
(Type I evidence – systematic review of 21 studies, two of which were randomized controlled trials.  Reviewed by DARE (record number 20000672) who note that it’s unclear why it is also stated that 5 RCTs were included.  15 studies (642 patients) were used in the outcome analysis and 16 (1,073 patients) in the mortality analysis)

top

5.6c.  An retrospective observational study suggested that long-term survival is similar for patients with atrial fibrillation, whether they receive drug therapy or (for those patients refractory to drug therapy), radio-frequency ablation of the atrioventricular node and implantation of a permanent pacemakeri i.  Ozcan C, Jahangir A, Friedman PA et al.  Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation.  New England Journal of Medicine  2001; 344(14): 1043-1051
(Type IV evidence – retrospective observational study of 350 patients (mean age 68±11 years) who underwent ablation of the atrioventricular node and implanatation of a permanent pacemaker at the Mayo Clinic between 1990 and 1998 compared to 229 controls (mean age 67±12 years) who received drug therapy.  Mean follow-up 36±26 months)
5.7  Evidence-based guidelines
5.7a.  Combined US/European guidelines for the management of patients with atrial fibrillation are availablei.

A companion paper includes a detailed algorithm for treatmentii.
Caveat: 
It is unclear whether the algorithm has been piloted with potential users.

i.  Fuster V, Ryden LE, Asinger RW et al. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients with Atrial Fibrillation). European Heart Journal 2001; 22(20):1852-1923.
(Evidence-based guidelines -  Authoritative consensus guidelines based on a systematic review of the literature, literature search to June 2000.  May lack multiprofessional and patient input)
Also published in:  Circulation 2001; 104(17):2118-2150, Journal of the American College of Cardiology 2001; 38(4):1266
Executive summary available:  http://www.acc.org/clinical/guidelines/
atrial_fib/exec_summ/exec_afindex.htm 
[accessed 22.12.03]
ii.  Peters NS, Schilling RJ, Kanagaratnam P, Markides V.  Atrial fibrillation: strategies to control, combat, and cure.  Lancet  2002; 359: 593-603
(Evidence Based Guidelines and Algorithm – based on a systematic literature search to November 2001)
5.7b.  Expert consensus guidelines are available for the use of antithrombotic therapy in atrial fibrillationi. i.  Albers GW, Dalen JE, Laupacis A, Manning WJ, Petersen P, Singer DE.  Sixth ACCP Consensus Conference on Antithrombotic Therapy. Antithrombotic therapy in atrial fibrillation.  Chest  2001; 119: 194S-206S
(Type V evidence – consensus guidelines)

 top


Contents Home

Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: mannmk@cf.ac.uk