Atrial Fibrillation

I am not a huge fan of interventions in AF like surgery and blood thinners, as I don't see the kind of results I'd like. There may be less intensive helpful interventions.


Am J Cardiol. 2011 May 3. [Epub ahead of print]

Non-Pharmacologic Management of Atrial Fibrillation.

Brenyo AJ, Aktas MK.

SourceUniversity of Rochester Medical Center, Strong Memorial Hospital, Department of Cardiovascular Diseases, Rochester, New York.


Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice today. Contemporary medical treatment options include atrioventricular nodal blocking agents to control heart rates during AF, antiarrhythmic drugs aimed at maintaining normal sinus rhythm, and anticoagulation therapies to reduce stroke risk. Invasive treatment of AF has emerged because of the toxicities and lack of long-term efficacy of available antiarrhythmic medications along with the lack of improvement in symptoms for rate-controlled patients. The investigators review the evolution of the current catheter-delivered AF procedures, starting with surgical maze up to and including left atrial appendage occlusion devices. Individual catheter ablation targets, anatomic and electrophysiologic, are discussed, with a particular focus on the use of an incremental ablation target strategy dependent on the type of AF being treated. In conclusion, the history of invasive AF therapy provides a basic understanding of contemporary ablation strategies and a backdrop for the cutting-edge rhythm and stroke prevention therapies of today.

Copyright © 2011 Elsevier Inc. All rights reserved.


J Cardiovasc Electrophysiol. 2011 Mar 15. doi: 10.1111/j.1540-8167.2011.02035.x. [Epub ahead of print]

Patients Treated with Catheter Ablation for Atrial Fibrillation Have Long-Term Rates of Death, Stroke, and Dementia Similar to Patients Without Atrial Fibrillation.

Bunch TJ, Crandall BG, Weiss JP, May HT, Bair TL, Osborn JS, Anderson JL, Muhlestein JB, Horne BD, Lappe DL, Day JD.

SourceIntermountain Heart Rhythm Specialists Department of Cardiology, Intermountain Medical Center, Murray, Utah, USA.


Outcomes in Patients With AF. Introduction: Atrial fibrillation (AF) adversely impacts mortality, stroke, heart failure, and dementia. AF ablation eliminates AF in most patients. We evaluated the long-term impact of AF ablation on mortality, heart failure (HF), stroke, and dementia in a large system-wide patient population. Methods: A total of 4,212 consecutive patients who underwent AF ablation were compared (1:4) to 16,848 age/gender matched controls with AF (no ablation) and 16,848 age/gender matched controls without AF. Patients were enrolled from the large ongoing prospective Intermountain AF study and were followed for at least 3 years. Results: Of the 37,908 patients, mean age 65.0 ± 13 years, 5,667 (14.9%) died, 1,296 (3.4%) had a stroke, and 1,096 (2.9%) were hospitalized for HF over >3 years of follow-up. AF ablation patients were less likely to have diabetes, but were more likely to have hypertension, HF, and significant valvular heart disease. AF ablation patients had a lower risk of death and stroke in comparison to AF patients without ablation. Alzheimer's dementia occurred in 0.2% of the AF ablation patients compared to 0.9% of the AF no ablation patients and 0.5% of the no AF patients (P < 0.0001). Other forms of dementia were also reduced significantly in those treated with ablation. Compared to patients with no AF, AF ablation patients had similar long-term rates of death, dementia, and stroke. Conclusions: AF ablation patients have a significantly lower risk of death, stroke, and dementia in comparison to AF patients without ablation. AF ablation may eliminate the increased risk of death and stroke associated with AF. (J Cardiovasc Electrophysiol, Vol. pp. 1-7).

© 2011 Wiley Periodicals, Inc.



Am J Cardiol. 2011 Apr 28. [Epub ahead of print]

Meta-Analysis of Obstructive Sleep Apnea as Predictor of Atrial Fibrillation Recurrence After Catheter Ablation.

Ng CY, Liu T, Shehata M, Stevens S, Chugh SS, Wang X.

SourceCedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.


The association between obstructive sleep apnea (OSA) and atrial fibrillation (AF) is strong and is now well established. However, studies on the role of OSA on AF recurrence after catheter ablation have yielded conflicting results. The aim of the present study was to investigate the role of OSA on AF recurrence after catheter-based pulmonary vein isolation. We performed a data search on the PubMed, Web of Science, and the Cochrane databases for studies published by August 2010. In addition, we manually searched the conference proceedings of the European Society of Cardiology, American College of Cardiology, and American Heart Association for related abstracts. After the initial search returned 402 reports, we identified 6 studies with a total of 3,995 patients that met our inclusion criteria. Overall, patients with OSA have a 25% greater risk of AF recurrence after catheter ablation than those without OSA (risk ratio 1.25, 95% confidence interval 1.08 to 1.45, p = 0.003). Subgroup analysis showed that OSA diagnosed using polysomnography is a strong predictor of AF recurrence (risk ratio 1.40, 95% confidence interval 1.16 to 1.68, p = 0.0004) but not when OSA was diagnosed using the Berlin questionnaire (risk ratio 1.07, 95% confidence interval 0.91 to 1.27, p = 0.39). In conclusion, patients with OSA have significantly greater AF recurrence rates after pulmonary vein isolation. In addition to other factors, a diagnosis of OSA merits special consideration when evaluating patients for catheter-based AF ablation.

Copyright © 2010 Elsevier Inc. All rights reserved.



Health Technol Assess. 2008 Nov;12(34):iii-iv, xi-xiii, 1-198.

Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation.

Rodgers M, McKenna C, Palmer S, Chambers D, Van Hout S, Golder S, Pepper C, Todd D, Woolacott N.

SourceCentre for Reviews and Dissemination, University of York, UK.


OBJECTIVES: To determine the safety, clinical effectiveness and cost-effectiveness of radio frequency catheter ablation (RCFA) for the curative treatment of atrial fibrillation (AF) and typical atrial flutter.

DATA SOURCES: For the systematic reviews of clinical studies 25 bibliographic databases and internet sources were searched in July 2006, with subsequent update searches for controlled trials conducted in April 2007. For the review of cost-effectiveness a broad range of studies was considered, including economic evaluations conducted alongside trials, modelling studies and analyses of administrative databases.

REVIEW METHODS: Systematic reviews of clinical studies and economic evaluations of catheter ablation for AF and typical atrial flutter were conducted. The quality of the included studies was assessed using standard methods. A decision model was developed to evaluate a strategy of RFCA compared with long-term antiarrhythmic drug (AAD) treatment alone in adults with paroxysmal AF. This was used to estimate the cost-effectiveness of RFCA in terms of cost per quality-adjusted life-year (QALY) under a range of assumptions. Decision uncertainty associated with this analysis was presented and used to inform future research priorities using the value of information analysis.

RESULTS: A total of 4858 studies were retrieved for the review of clinical effectiveness. Of these, eight controlled studies and 53 case series of AF were included. Two controlled studies and 23 case series of typical atrial flutter were included. For atrial fibrillation, freedom from arrhythmia at 12 months in case series ranged from 28% to 85.3% with a weighted mean of 76%. Three RCTs suggested that RFCA is more effective than long-term AAD therapy in patients with drug-refractory paroxysmal AF. Single RCTs also suggested superiority of RFCA over electrical cardioversion followed by long-term AAD therapy and of RFCA plus AAD therapy over AAD maintenance therapy alone in drug-refractory patients. The available RCTs provided insufficient evidence to determine the effectiveness of RFCA beyond 12 months or in patients with persistent or permanent AF. Adverse events and complications were generally rare. Mortality rates were low in both RCTs and case series. Cardiac tamponade and pulmonary vein stenosis were the most frequently recorded complications. For atrial flutter, freedom from arrhythmia at 12 months in case series ranged from 85% to 92% with a weighted mean of 88%. Neither of the atrial flutter RCTs reported freedom from arrhythmia at 12 months. One RCT found a statistically significant benefit favouring ablation over AADs in terms of freedom from arrhythmia at a mean follow-up of 22 months. A second RCT reported a more modest effect favouring ablation in terms of freedom from atrial flutter at follow-up in older patients (mean age 78 years) after their first episode of flutter. In the atrial flutter case series, mortality was rare and the most frequent complications were atrioventricular block and haematomas. Complications in the RCTs were similar, except for those events likely to have been caused by AAD therapy (e.g. thyroid dysfunction). The review of cost-effectiveness evidence found one relevant study, which from a UK NHS perspective had a number of important limitations. The base-case analysis in the decision model demonstrated that if the quality of life benefits of RFCA are maintained over the remaining lifetime of the patient then the cost-effectiveness of RFCA appears clear. These findings were robust over a wide range of alternative assumptions, being between 7763 and 7910 pounds per additional QALY with very little uncertainty. If the quality of life benefits of RFCA are assumed to be maintained for no more than 5 years, cost-effectiveness of RFCA is dependent on a number of factors. Estimates of cost-effectiveness that explored the influence of these factors ranged from 23,000 to 38,000 pounds per QALY.

CONCLUSIONS: RFCA is a relatively safe and efficacious procedure for the therapeutic treatment of AF and typical atrial flutter. There is some randomised evidence to suggest that RFCA is superior to AADs in patients with drug-refractory paroxysmal AF in terms of freedom from arrhythmia at 12 months. RFCA appears to be cost-effective if the observed quality of life benefits are assumed to continue over a patient's lifetime. However, there remain uncertainties around longer-term effects of the intervention and the extent to which published effectiveness findings can be generalised to 'typical' UK practice. All catheter ablation procedures for the treatment of AF or atrial flutter undertaken in the UK should be recorded prospectively and centrally and measures to increase compliance in recording RFCA procedures may be needed. This would be of particular value in establishing the long-term benefits of RFCA and the true incidence and impact of any complications. Collection of appropriate quality of life data within any such registry would also be of value to future clinical and cost-effectiveness research in this area. Any planned multicentre RCTs comparing RFCA against best medical therapy for the treatment of AF and/or atrial flutter should be conducted among 'non-pioneering' centres using the techniques and equipment typically employed in UK practice and should measure relevant outcomes.


Am Heart J. 2009 Jul;158(1):15-20.

Mortality after catheter ablation for atrial fibrillation compared with antiarrhythmic drug therapy. A meta-analysis of randomized trials.

Dagres N, Varounis C, Flevari P, Piorkowski C, Bode K, Rallidis LS, Tsougos E, Leftheriotis D, Sommer P, Hindricks G, Kremastinos DT.

SourceUniversity of Athens, Second Cardiology Department, Attikon University Hospital, Rimini 1, Haidari, Athens, Greece.


INTRODUCTION: Nonrandomized studies suggest a survival benefit for patients with atrial fibrillation (AF) undergoing catheter ablation compared with antiarrhythmic drug (AAD) therapy. Data from randomized trials are lacking. We performed a meta-analysis on mortality in randomized controlled trials comparing AF ablation with AADs.

METHODS: Pubmed, the Cochrane Central Register of Controlled Trials, and abstracts of major conferences were searched for randomized trials comparing AF catheter ablation with AADs. Eight trials with a total of 930 patients were analyzed. Trial quality was assessed by a modified Jadad scale. Follow-up was 1 year in most trials. We assessed fixed effect risk differences (RDs) with the Mantel-Haenzel method, heterogeneity with I(2) statistic, and publication bias with Begg's funnel plot and with Egger's test.

RESULTS: A total of 7 deaths were reported: 3 in the ablation and 4 in the AAD arm. There was no difference in mortality between AF ablation and AAD therapy. The RD of mortality in all trials between patients randomized to ablation and those randomized to AADs was -0.003 (95% CI -0.018 to 0.013, P = .74) without evidence for heterogeneity (I(2) = 0%, P = .907). No potential publication bias was found. There was also no difference in rates of stroke or transient ischemic attack between ablation and antiarrhythmic therapy for AF (RD = 0.004, 95% CI -0.010 to 0.018, P = .54).

CONCLUSION: This meta-analysis of randomized controlled trials showed similar survival of patients undergoing catheter ablation for AF compared with patients treated with AADs after 12 months of follow-up. There was also no difference in the rates of stroke or transient ischemic attack. These findings can be probably explained by the low-risk young populations who were included in the trials and the relatively short 12-month follow-up.




Am J Cardiol. 2010 Feb 15;105(4):502-10.

Thromboembolism in atrial fibrillation.

Menke J, Lüthje L, Kastrup A, Larsen J.

SourceUniversity Hospital, Göttingen, Germany.


Thromboembolism is a severe complication in atrial fibrillation. This overview presents thromboembolic disease as a single entity, ranging from stroke through mesenteric ischemia to acute limb ischemia. The PubMed, Embase, and Cochrane databases were systematically searched for the terms "atrial fibrillation" and "thromboembolism" in reports published from January 1986 to September 2009. The information of 10 evidence-based practice guideline documents and 61 further sources was systematically extracted. In atrial fibrillation, the average annual stroke risk is increased by 2.3% (lethality 30%). The annual incidence of acute mesenteric ischemia is 0.14% (lethality 70%), and that of acute limb ischemia is 0.4% (lethality 16%). In total, approximately 80% of embolism-related deaths are from stroke and 20% from other systemic thromboembolism. The ischemic symptoms generally have an acute onset but may mimic other diseases, particularly in mesenteric ischemia. Early diagnosis and treatment can limit or even prevent tissue infarction. Guideline-recommended therapy with aspirin or warfarin reduces the thromboembolic risk. Suitable patients may optimize their warfarin therapy by self-monitoring of the international normalized ratio (INR). New oral and parenteral anticoagulants with more stable pharmacokinetics are being developed. In conclusion, atrial fibrillation predisposes to thromboembolism. If ischemic stroke or systemic thromboembolism occurs, early diagnosis and treatment can improve outcomes. The thromboembolic risks are reduced by guideline-adherent antithrombotic therapy with warfarin or aspirin. Future directions may include self-monitoring of the international normalized ratio and novel anticoagulants.

Copyright 2010 Elsevier Inc. All rights reserved.


BMJ. 2001 Feb 10;322(7282):321-6. Related Articles, Links

Erratum in:

BMJ. 2001 Mar 10;322(7286):587.

Comment in:

ACP J Club. 2001 Sep-Oct;135(2):60.

BMJ. 2001 Jul 28;323(7306):233-4; author reply 235-6.

BMJ. 2001 Jul 28;323(7306):233; author reply 235-6.

BMJ. 2001 Jul 28;323(7306):234-5; author reply 235-6.

BMJ. 2001 Jul 28;323(7306):234; author reply 235-6.

BMJ. 2001 Jul 28;323(7306):234; author reply 235-6.

BMJ. 2001 Jul 28;323(7306):234; author reply 235-6.

BMJ. 2001 Jul 28;323(7306):235-6.

Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation.

Taylor FC, Cohen H, Ebrahim S.

Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW.

OBJECTIVE: To examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indobufen) [corrected] in patients with non-rheumatic atrial fibrillation. METHODS: Meta-analysis of randomised controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle from 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to estimate treatment effects. OUTCOME MEASURES: Fatal and non-fatal cardiovascular events, reductions of which were classified as benefits. Fatal and major non-fatal bleeding events classified as risks. RESULTS: No trials were found from before 1989. There were five randomised controlled trials published between 1989-99. There were no significant differences in mortality between the two treatment options (fixed effects model: odd ratio 0.74 (95% confidence interval 0.39 to 1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a borderline significant difference in non-fatal stroke in favour of anticoagulation (0.68 (0.46 to 0.99)); and 0.75 (0.50 to 1.13) after exclusion of one trial with weak methodological design. A random effects model showed no significant difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)). There were more major bleeding events among patients on anticoagulation than on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped prematurely after a significant difference in favour of anticoagulation was observed. The only trial to show a significant difference in effect (favouring anticoagulation) was methodologically weaker in design than the others. CONCLUSIONS: The heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option.

Publication Types:


PMID: 11159653 [PubMed - indexed for MEDLINE]

Cochrane Database Syst Rev. 2000;(2):CD001927. Related Articles, Links

Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.

Benavente O, Hart R, Koudstaal P, Laupacis A, McBride R.

Division of Neurology, Department of Medicine, University of Texas. Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7883, USA. .

BACKGROUND: Non-valvular atrial fibrillation (AF) is associated with an increased risk of stroke. OBJECTIVES: The objective of this review was to characterize the efficacy and safety of oral anticoagulation (OAC) with vitamin K antagonists for the primary prevention of stroke in patients with chronic AF. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Register of Trials (June 1999), MEDLINE database, and the database of the Antithrombotic Trialists Collaboration, as well as reference lists of relevant articles. SELECTION CRITERIA: All randomized controlled trials comparing the value of OAC versus control in patients with non-valvular chronic atrial fibrillation and no history of transient ischemic attack (TIA) or stroke. DATA COLLECTION AND ANALYSIS: Trials for inclusion were independently selected by two reviewers who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, "intention-to-treat". Since the published results of four trials included 3-8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators. MAIN RESULTS: Of 2313 participants without prior cerebral ischemia from five trials, about half (n = 1154) were randomized to adjusted-dose OAC with an estimated mean INRs ranging between 2.0-2.6 during 1.5 years/participant average follow-up. Participant features and study quality were similar between trials. OAC was associated with large, highly statistically significant reductions in ischemic stroke (OR = 0.34, 95% CI 0.23 - 0.52), all stroke (OR = 0.39, 95% CI 0.26 - 0. 59), all disabling or fatal stroke (OR = 0.47, 95% CI 0.28 - 0.80), and the combined endpoint of all stroke, MI or vascular death (OR = 0.56, 95% CI 0.42 - 0.76). The observed rates of intracranial and extracranial hemorrhage not significantly increased by OAC therapy, but confidence intervals were wide. REVIEWER'S CONCLUSIONS: Adjusted-dose OAC (achieved INRs between 2-3) reduces stroke as well as disabling/fatal stroke for patients with nonvalvular AF, and these benefits were not substantially offset by increased bleeding among participants in randomized clinical trials. Limitations include relatively short follow-up and imprecise estimates of bleeding risks from these selected participants. For primary prevention in AF patients who have an average stroke rate of 4%/year, about 25 strokes and about 12 disabling fatal strokes would be prevented yearly for every 1000 given OAC.

Publication Types:


Review, Academic

PMID: 10796453 [PubMed - indexed for MEDLINE]

Cochrane Database Syst Rev. 2000;(2):CD001925. Related Articles, Links

Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.

Benavente O, Hart R, Koudstaal P, Laupacis A, McBride R.

Division of Neurology, Department of Medicine, University of Texas. Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7883, USA.

BACKGROUND: Atrial fibrillation (AF) carries an increased risk of stroke; antiplatelet agents are proven effective for stroke prevention in other settings. OBJECTIVES: The objective of this review was to determine the efficacy and safety of antiplatelet therapy for prevention of stroke in patients with chronic non-valvular AF. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Register of Trials, MEDLINE database (June 1999), and the database of the Antithrombotic Trialists Collaboration, as well as reference lists of relevant articles. SELECTION CRITERIA: All randomized trials comparing antiplatelet therapies to placebo in patients with non-valvular AF and no history of transient ischemic attack (TIA) or stroke. DATA COLLECTION AND ANALYSIS: Trials for inclusion were independently selected by two reviewers who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, "intention-to-treat". Since the published results of two trials included 3-8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators. MAIN RESULTS: Among 1680 participants without prior stroke/TIA, randomized to aspirin (N = 838) or placebo in two trials, aspirin was associated with nonsignificantly lower risks of ischemic stroke (OR = 0.71, CI 95% 0. 46 - 1.10), all stroke (OR = 0.70, CI 95% 0.45 - 1.08) all disabling/fatal stroke (OR =0.88, CI 95% 0.48 - 1.58) and the constellation of stroke, MI or vascular death (OR = 0.76, CI 95% 0. 54 - 1.05 ). Considering all randomized participants including those with prior stroke or TIA, reductions in these events by aspirin were consistently smaller and marginally statistically significant: ischemic stroke (OR = 0.77, CI 95% 0.60-1.00), all stroke (OR = 0.76, CI 95% 0.61 - 0.93), all disabling/fatal stroke (OR = 0.87, CI 95% 0.64 - 1.19) and the combined outcome (OR = 0.79, CI 95% 0.64 - 0. 99). No increase in major hemorrhage was seen, but the number of hemorrhagic events was small. REVIEWER'S CONCLUSIONS: Considering all randomized data, aspirin modestly (by about 20%) reduces stroke and major vascular events in nonvalvular AF. For primary prevention among AF patients with an average stroke rate of 4.5%/year, about 10 strokes would be prevented yearly for every 1000 given aspirin.

Publication Types:


Review, Academic

PMID: 10796452 [PubMed - indexed for MEDLINE]

Cochrane Database Syst Rev. 2001;(1):CD001938. Related Articles, Links

Anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter.

Segal JB, McNamara RL, Miller MR, Powe NR, Goodman SN, Robinson KA, Bass EB.

Medicine, Johns Hopkins School of Medicine, 1830 E. Monument St. 8th floor, Baltimore, Maryland 21205, USA.

BACKGROUND: Atrial fibrillation (AF) carries a high risk of stroke and other thromboembolic events. Appropriate use of drugs to prevent thromboembolism in patients with AF involves comparing the patient's risk of stroke to the risk of hemorrhage from medication use. OBJECTIVES: To quantify risk of stroke, major hemorrhage and death from using medications that have been rigorously evaluated for prevention of thromboembolism in AF. SEARCH STRATEGY: Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until December 1999. SELECTION CRITERIA: Included Randomized controlled trials of drugs to prevent thromboembolism in adults with non-postoperative AF. Excluded RCTS of patients with rheumatic valvular disease. DATA COLLECTION AND ANALYSIS: Data were abstracted by two reviewers. Odds ratios from all qualitatively similar studies were combined, with weighting by study size, to yield aggregate odds ratios for stroke, major hemorrhage, and death for each drug. MAIN RESULTS: Fourteen articles were included in this review. Warfarin was more efficacious than placebo for primary stroke prevention [aggregate odds ratio (OR) of stroke=0.30 [95% Confidence Interval (C.I.) 0.19,0.48]], with moderate evidence of more major bleeding [ OR= 1.90 [95% C.I. 0.89,4.04].]. Aspirin was inconclusively more efficacious than placebo for stroke prevention [OR=0.68 [95% C.I. 0.29,1.57]], with inconclusive evidence regarding more major bleeds [OR=0.81[95% C.I. 0.37,1.78]]. For primary prevention, assuming a baseline risk of 45 strokes per 1000 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% C.I. 0.43,0.96]], with only suggestive evidence for more major hemorrhage [OR =1.58 [95% C.I. 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 1000 person-years) compared to an older group (15 per 1000 person-years). Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarin. REVIEWER'S CONCLUSIONS: The evidence strongly supports warfarin in AF for patients at average or greater risk of stroke, although clearly there is a risk of hemorrhage. Although not definitively supported by the evidence, aspirin may prove to be useful for stroke prevention in sub-groups with a low risk of stroke, with less risk of hemorrhage than with warfarin. Further studies are needed of low- molecular weight heparin and aspirin in lower risk patients.

Publication Types:


Review, Academic

PMID: 11279741 [PubMed - indexed for MEDLINE]

Ann Intern Med. 2003 Dec 16;139(12):1018-33. Related Articles, Links

Comment in:

Ann Intern Med. 2003 Dec 16;139(12):I32.

Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography.

McNamara RL, Tamariz LJ, Segal JB, Bass EB.

Cardiovascular Section, Yale University School of Medicine, New Haven, Connecticut 06520-8017, USA.

PURPOSE: This review summarizes the available evidence regarding the efficacy of medications used for ventricular rate control, stroke prevention, acute conversion, and maintenance of sinus rhythm, as well as the efficacy of electrical cardioversion and the use of echocardiography in patients with atrial fibrillation. DATA SOURCES: The Cochrane Collaboration's database of controlled clinical trials and MEDLINE. STUDY SELECTION: Primarily randomized, controlled trials of medications. DATA EXTRACTION: Paired reviewers obtained data on efficacy and safety. Strength of evidence was assessed. DATA SYNTHESIS: Recent clinical trial results showed that most patients with atrial fibrillation have similar outcomes with strategies for controlling ventricular rate compared with strategies for restoring sinus rhythm. For efficacy of primary stroke prevention, compared with placebo, evidence was strong for warfarin and suggestive for aspirin. The evidence for an increased risk for major bleeding was suggestive for warfarin and inconclusive for aspirin. For ventricular rate control, verapamil, diltiazem, atenolol, and metoprolol were qualitatively superior to digoxin and placebo, particularly during exercise. For efficacy of acute conversion, compared with placebo, evidence was strong for ibutilide, flecainide, dofetilide, propafenone, amiodarone, and quinidine. For efficacy of maintenance of sinus rhythm after conversion from atrial fibrillation, evidence was strong for amiodarone, propafenone, disopyramide, and sotalol. Echocardiography was found to be useful in estimating risk for thromboembolism and potentially useful in estimating likelihood of successful cardioversion and maintenance. CONCLUSIONS: For several key questions in the pharmacologic management of atrial fibrillation, strong evidence exists to support 1 or more treatment options.

Publication Types:


Review, Academic

PMID: 14678922 [PubMed - indexed for MEDLINE]

Arch Intern Med. 2002 Mar 11;162(5):541-50.

Balancing the risks of stroke and upper gastrointestinal tract bleeding in older patients with atrial fibrillation.

Man-Son-Hing M, Laupacis A.

SourceDepartment of Medicine, University of Ottawa, Geriatric Assessment Unit, Ottawa Research Institute, Ottawa Hospital (Civic Campus), 1053 Carling Ave, Ottawa, Ontario, Canada K1Y 4E9.


OBJECTIVE: To determine how factors that increase the risk of major upper gastrointestinal (GI) tract hemorrhage (recent upper GI tract bleeding or concurrent use of nonsteroidal anti-inflammatory drugs) influence the choice of antithrombotic therapy in older patients (those > or = 65 years) with atrial fibrillation.

METHODS: For older patients with atrial fibrillation and no other contraindications to antithrombotic therapy, a Markov decision-analytic model was used to determine the preferred treatment strategy (no antithrombotic therapy, long-term aspirin use, or long-term warfarin sodium use) based on their risk of major upper GI tract hemorrhage. Input data were obtained by a systematic review of MEDLINE. Outcomes were expressed as quality-adjusted life-years (QALYs).

RESULTS: For 65-year-old patients with average risks of stroke and upper GI tract bleeding, warfarin therapy was associated with 12.1 QALYs per patient; aspirin therapy, 10.8 QALYs; and no antithrombotic therapy, 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; and no treatment, 7.21 QALYs).

CONCLUSIONS: For older patients with atrial fibrillation and factors that place them at a higher than average risk of upper GI tract bleeding, the optimal choice of antithrombotic therapy to prevent stroke can vary according to the magnitude of this risk. Based on the risks of stroke and upper GI tract bleeding, clinicians can use the treatment recommendations of this study to provide rational stroke prevention therapy for older patients with atrial fibrillation.


Cochrane Database Syst Rev. 2002;(1):CD002903. Related Articles, Links

J Manag Care Pharm. 2009 Apr;15(3):244-52.

Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States.

Baker WL, Cios DA, Sander SD, Coleman CI.

SourceUniversity of Connecticut/Hartford Hospital Evidence-Based Practice Center, Hartford, CT 06102, USA.


BACKGROUND: Atrial fibrillation (AF) affects a significant proportion of the American population and increases ischemic stroke risk by 4- to 5-fold. Oral vitamin K antagonists, such as warfarin, can significantly reduce this stroke risk but can be difficult to dose and monitor. Previous research on the effects of setting (e.g., randomized controlled trials, anticoagulation management by specialty clinics, usual care by community physicians) on the proportion of time spent within therapeutic range for the international normalized ratio (INR) has not specifically examined anticoagulation in AF patients.

OBJECTIVES: Use traditional meta-analytic and meta-regressive techniques to evaluate the effect of specialty clinic versus usual care by community physicians on anticoagulation control, measured as the proportion of time spent in therapeutic INR range, for AF patients that received warfarin anticoagulation in the United States.

METHODS: Studies included in a previously published meta-analysis (van Walraven et al., 2006), which systematically searched reports between 1987 and 2005, were also screened for inclusion in our analysis. A subsequent systematic literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Clinical Trials from January 2005 through February 2008 was conducted. Studies were included if they (a) contained at least 1 warfarin-treated group including more than 25 patients for whom INR control was monitored for at least 3 weeks; (b) included patients treated for AF in the United States; (c) used a patient-time approach (patient-year) to report outcomes; and (d) reported data on the proportion of time spent in traditional therapeutic INR ranges (i.e., a lower limit INR between 1.8 and 2.0 and an upper limit INR between 3.0 and 3.5. Studies with INR goals outside this range were excluded). The proportion of time spent within the therapeutic INR range for each study group was expressed as an incidence density using a person-time approach (in years). All studies were pooled using a random effects model and were weighted by the inverse of the variance of proportion of time spent in the therapeutic range. In order to determine how study setting influenced the proportion of time spent within a therapeutic INR range, both subgroup and meta-regression analyses were conducted.

RESULTS: This analysis included 8 studies and a total of 14 unique warfarin- treated groups; 3 of the 8 studies and 4 of the warfarin groups were not included in the previous meta-analysis (van Walraven et al., 2006). Overall, patients spent a mean 55% (95% CI = 51%-58%) of their time in the therapeutic INR range. Meta-regression suggested that AF patients treated in a community usual care setting compared with an anticoagulation clinic spent 11% (95% CI = 2%-20%, n = 6 studies with 9 study groups) less time in range.

CONCLUSIONS: In the United States, AF patients spend only about one-half the time within therapeutic INR. Anticoagulation clinic services are associated with somewhat better INR control compared with standard community care.


Electrical cardioversion for atrial fibrillation and flutter.

Mead GE, Flapan AD, Elder AT.

Clinical and Surgical Sciences, University of Edinburgh, 21 Chalmers Street, Edinburgh, UK, EH3 9EW.

BACKGROUND: Atrial fibrillation increases the risk of stroke, increases the risk of cognitive impairment, and adversely affects cardiovascular haemodynamics. Electrical cardioversion for atrial fibrillation has been in use since the 1960s; the rationale is that restoration of sinus rhythm improves cardiovascular haemodynamics, reduces the risk of stroke, and obviates the need for long-term anticoagulation. OBJECTIVES: To assess the effects of electrical cardioversion of atrial fibrillation or atrial flutter on the annual risk of thromboembolic events, strokes and mortality (primary outcomes measures), the rate of cognitive decline, quality of life, the use of anticoagulants and the risk of re-hospitalisation (secondary outcome measures) in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and any aetiology. SEARCH STRATEGY: One reviewer searched the Cochrane Controlled Clinical Trials Register (2000 Issue 4), MEDLINE (1966 to December 2000), EMBASE (1980 to December 2000), CINAHL (1982 to November 2000) and proceedings of the American College of Cardiology (published in the Journal of the American College of Cardiology 1983 to 2000). Reference lists of articles were searched. Personal contact was made with experts in the field. A second reviewer handsearched proceedings of the British Cardiac Society (published in British Heart Journal (1980 to 1995) and in Heart (1995 to May 2001); proceedings of the European Congress of Cardiology and meetings of the Joint Working Groups of the European Society of Cardiology (published in European Heart Journal 1983-2000); scientific sessions of the American Heart Association (published in Circulation 1990-2000). SELECTION CRITERIA: Randomised controlled trial or controlled clinical trials of electrical cardioversion plus 'usual care' versus 'usual care' only, where 'usual care' included any combination of the following: anticoagulants, antiplatelet drugs and drugs for 'rate control', in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and any aetiology. DATA COLLECTION AND ANALYSIS: It was planned to extract study data onto data extraction forms. The planned analysis was by the statistical package in RevMan. MAIN RESULTS: No completed randomised trials or controlled clinical trials of electrical cardioversion were found. Two ongoing trials were identified. REVIEWER'S CONCLUSIONS: There were no data from completed randomised controlled trials or controlled clinical trials to either support or refute the use of electrical cardioversion for atrial fibrillation. Randomised trials of electrical cardioversion are required.

Publication Types:


Review, Academic

PMID: 11869642 [PubMed - indexed for MEDLINE]

Am J Geriatr Cardiol. 2003 Jan-Feb;12(1):49-56. Related Articles, Links

Atrial fibrillation in the elderly.

Yadav A, Scheinman M.

Department of Medicine, Division of Cardiology, Cardiac Electrophysiology Section, University of California at San Francisco, San Francisco, CA 94143, USA.

Atrial fibrillation is the most common arrhythmia in the United States, whose incidence is greatest in the elderly population. This rhythm disorder can be paroxysmal or chronic and is associated with a range of clinical conditions from palpitations and dyspnea to stroke and death. In the elderly the mainstay of treatment of atrial fibrillation should utilize drug therapy. The main goals of drug therapy should be effective rate control to avoid tachycardia-induced cardiomyopathy, anticoagulation to reduce the risk of stroke and thromboembolism, and maintenance of sinus rhythm to prevent adverse atrial remodeling. In those patients in whom effective rate control cannot be achieved, catheter ablation of the atrioventricular node and implantation of a permanent pacemaker should be considered. Catheter ablation of atrial fibrillation by targeting pulmonary venous foci or pulmonary venous isolation currently remains investigational and we advocate its use be limited to symptomatic patients who have failed traditional therapy. Copyright 2003 CVRR, Inc.

Publication Types:


Review, Tutorial

PMID: 12502916 [PubMed - indexed for MEDLINE]

Arch Fam Med. 2000 Apr;9(4):389-90. Related Articles, Links

Comment in:

Arch Fam Med. 2000 Jul;9(7):587-8.

Vagally mediated atrial fibrillation in a young man.

Ringdahl EN.

Department of Family and Community Medicine, University of Missouri, Columbia, USA.

Atrial fibrillation may be provoked by either vagal or sympathetic stimulation. Sympathetic effects are common in middle-aged and elderly patients with underlying heart disease. However, in the young, non-diseased heart, vagal influences are more likely to predominate. Recognition of vagally mediated atrial fibrillation in young adults as a unique clinical entity has diagnostic and therapeutic implications.

Publication Types:

Case Reports

PMID: 10776370 [PubMed - indexed for MEDLINE]

Chest. 1982 Apr;81(4):429-32. Related Articles, Links

Spontaneous conversion of long-standing atrial fibrillation.

Gardner JD, Dunn M.

Spontaneous conversion to sinus rhythm after prolonged atrial fibrillation is uncommon, with only 11 recorded cases to our knowledge in the English language literature. We report four cases of spontaneous conversion to an organized atrial rhythm (either sinus rhythm or atrial tachycardia with block) after nine to 16 years of established atrial fibrillation. One case was due to a toxic reaction to digitalis. In the other three cases there was no apparent reason. M-mode and two-dimensional echocardiography in three patients showed an akinetic and noncontractile left atrium in each case. This lends support to an earlier hypothesis that complete fibrosis of the left atrium may be responsible for the conversion from atrial fibrillation.

Publication Types:

Case Reports

PMID: 7067507 [PubMed - indexed for MEDLINE]

Pacing Clin Electrophysiol. 2001 Sep;24(9 Pt 1):1363-8. Related Articles, Links

Response of atrial fibrillatory activity to carotid sinus massage in patients with atrial fibrillation.

Bollmann A, Wodarz K, Esperer HD, Toepffer I, Klein HU.

Department of Cardiology, University Hospital Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.

In some cases carotid sinus massage (CSM) may induce AF, whereas it may terminate AF in others. The purpose of this study was to investigate the influence of CSM on atrial fibrillatory frequency using spectral analysis of the surface ECG. Continuous ECG recordings were made in 19 patients (12 men, 7 women, mean age 61 +/- 11 years) with AF. Unilateral CSM was performed in the standard fashion to one randomized bifurcation of the carotid artery at a time. Ventricular rate and fibrillatory frequency were assessed in 30-second ECG segments at baseline and during CSM. The frequency content of the fibrillatory baseline was quantified using digital signal processing (filtering, subtraction of averaged QRST complexes, and Fourier transformation). CSM resulted in a relative change in fibrillatory frequency of 4.5 +/- 3.9% (range 0%-13%). In 8 (42%) patients an increase in fibrillatory frequency was found (6.4 +/- 0.5 vs 6.8 +/- 0.5 Hz, P = 0.012). In 9 (47%) patients a decrease in fibrillatory frequency occurred (6.5 +/- 0.8 vs 6.1 +/- 0.8 Hz, P = 0.008) without AF termination. The remaining two patients showed no change in fibrillatory frequency. CSM on the contralateral side after 2 minutes produced fibrillatory frequency changes in the same direction in all patients with a good reproducibility in its magnitude (r = 0.59, P = 0.05). Calcium channel blockers were more frequently used (78% vs 25%, P = 0.044) in patients with a decrease in fibrillatory frequency compared to patients with a frequency increase. There were no significant changes in ventricular rate during CSM. In conclusion, two different responses of atrial fibrillatory frequency to CSM were found. This might explain why CSM may facilitate AF induction in some cases and AF termination in others. Calcium channel blocker treatment may prevent an increase in fibrillatory frequency provoked by CSM suggesting a blunted electrical remodeling process.

PMID: 11584458 [PubMed - indexed for MEDLINE]

Int J Clin Pract. 2001 Mar;55(2):108-14. Related Articles, Links

Comment in:

Int J Clin Pract. 2001 Mar;55(2):77-8.

The old but reliable digitalis: persistent concerns and expanded indications.

Abarquez RF Jr.

College of Medicine, University of the Philippines, Manila, Philippines.

Digitalis has been an old but reliable drug for 240 years. Concerns regarding its clinical indications and benefits still exist in the absence of a reduction in all-cause mortality. While intravenous digitalis is used without question in cases of atrial fibrillation, it is still controversial in sinus rhythm, despite the Digitalis Investigation Group (DIG) study showing a significant reduction in death and the need for hospitalisation for congestive heart failure in both diastolic and systolic dysfunction. The influence of digitalis in acute myocardial infarction, coronary artery disease and sudden cardiac death remains speculative. In cases of uncomplicated hypertension, it appears to prevent the onset of left ventricular dysfunction and myocardial infarction. Thus, digitalis can be a cost-effective agent with added benefits.

Publication Types:


Review, Tutorial

PMID: 11321850 [PubMed - indexed for MEDLINE]

Nurs Times. 1994 Sep 21-27;90(38):36-7. Related Articles, Links

The use of massage in restoring cardiac rhythm.

Curtis M.

There is a growing body of research that connects heart rate and massage. These variously associate massage with reduced cardiac rate, lowered blood pressure, decreased anxiety and increases in relaxation and a sense of well-being. Dunbar and Redick looked specifically at back massage following myocardial infarction and Weiss reports a correlation between touch and heart rate during tracheal suctioning. This paper describes how massage was used to restore cardiac rhythm from a state of atrial fibrillation in one patient.

Publication Types:

Case Reports

PMID: 7971330 [PubMed - indexed for MEDLINE]

J Am Coll Cardiol. 1993 Oct;22(4):1123-9. Related Articles, Links

Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation.

Brignole M, Gianfranchi L, Menozzi C, Raviele A, Oddone D, Lolli G, Bottoni N.

Laboratory of Electrophysiology and Pacing, Ospedali Riuniti, Lavagna, Italy.

OBJECTIVES. The purpose of this study was to evaluate the role of autonomic reflexes in the genesis of syncope associated with the onset of paroxysmal atrial fibrillation. BACKGROUND. Syncope associated with paroxysmal atrial fibrillation has been interpreted as an ominous finding predictive of rapid ventricular rates. However, various mechanisms may be involved when heart rate is not particularly high. METHODS. Forty patients (age 60 +/- 14 years, 20 men, 20 women) with syncope and atrial fibrillation were compared with atrial fibrillation without syncope. Carotid sinus massage and head-up tilt testing (at 60 degrees for 60 min at baseline and during isoproterenol infusion) were performed during sinus rhythm. A positive response was defined as the induction of syncope. Atrial fibrillation was also induced on a tilt table at 60 degrees by means of short bursts of atrial pacing. RESULTS. Results of carotid sinus massage were positive in 15 (37%) of 40 patients but in no control subjects (p = 0.002). Head-up tilt test findings were positive in 25 (66%) of 38 patients and in 2 (12%) of 16 control subjects (p = 0.0004). The induction of atrial fibrillation in the upright position elicited syncope in 16 (42%) of 38 patients but in none of 16 control subjects (p = 0.001). At the beginning of atrial fibrillation, systolic blood pressure was lower in patients than in control subjects (88 +/- 32 vs. 127 +/- 32 mm Hg), whereas mean heart rate was similar (142 +/- 35 vs. 134 +/- 25 beats/min). The correlation between heart rate and systolic blood pressure was weak (r = 0.35), and in five patients syncope occurred at a heart rate < or = 130 beats/min. At the time of syncope, heart rate decreased (-12 +/- 21 beats/min) in patients with induced syncope, whereas it remained unchanged in patients without induced syncope (+1 +/- 17 beats/min, p = 0.04) or slightly increased in control subjects (+9 +/- 21 beats/min, p = 0.009). CONCLUSIONS. Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope.

PMID: 8409051 [PubMed - indexed for MEDLINE]

G Ital Cardiol. 1993 Oct;23(10):985-93. Related Articles, Links

[Hypersensitivity and carotid sinus syndrome in patients with chronic atrial fibrillation]

[Article in Italian]

Cicogna R, Mascioli G, Bonomi FG, Turelli A, Morandi F, Curnis A, Visioli O.

Cattedra e Divisione di Cardiologia, Universita Degli Studi e Spedali Civili, Brescia.

BACKGROUND. Carotid sinus hypersensitivity (CSH) has always been described in patients in sinus rhythm; we did not find reports of CSH in patients with chronic atrial fibrillation (AF). After the observation of bilateral CSH in a patient with chronic AF admitted to our Division for syncope, we began to systematically study patients with chronic AF and neurological disturbances to evaluate carotid sinus stimulation effects upon cardiac activity and arterial blood pressure in these subjects. METHODS. We studied 28 subjects with chronic AF (mean age 73.3 yrs.; range 60-89): 16 patients had dizziness, fainting or syncope, and formed the study group (A); 12 asymptomatic patients were considered the control group (B). After a careful clinical and instrumental evaluation, all the patients underwent a 24 hour ambulatory (Holter) ECG analysis and right and left carotid sinus massage (CSM). If the latter manoeuvre induced asystolia longer than 3 seconds, CSM was repeated during ventricular pacing to evaluate the vasal component of the carotid sinus reflex. RESULTS. In group A, 24-hour Holter monitoring showed a greater incidence (81.2%) of ventricular standstill (mean duration 2.67 seconds) in comparison to the control group. In group A we found CSH in 75% of the cases, more frequently right CSH (7 subjects with right, 1 with left and 4 with bilateral CSH) with prolonged ventricular asystolia (mean duration 5.3 +/- 1.9 sec. with right CSM; 7.8 +/- 1.4 sec. with left CSM); during CSM, we reproduced spontaneous symptomatology in 9 patients. In 12 patients in group A, diagnosis of carotid sinus syndrome was established; the cardioinhibitory forms were clearly prevalent (91.7%); only one patient presented a cardioinhibitory-vasodepressor form with a predominant vasodepressor component. CONCLUSIONS. The authors believe that CSH is frequent in patients with chronic AF; the vagal hyperactivity due to CSH can induce prolonged ventricular asystole that may be responsible for neurological disturbances such as dizziness, fainting or syncope, as observed in patients in sinus rhythm with carotid sinus syndrome. Abnormal sensitivity of the carotid sinus could thus be one of the causes of increased morbidity and mortality in patients with chronic AF. The majority of these patients may be expected to benefit from permanent pacemaker therapy.

PMID: 8174866 [PubMed - indexed for MEDLINE]

Biull Eksp Biol Med. 1987 Aug;104(8):151-3. Related Articles, Links

[Prevention of a stress-induced drop in the threshold of cardiac fibrillation using transauricular electroacupuncture]

[Article in Russian]

Radzievskii SA, Vorontsova EIa, Chuvil'skaia LM, Ustinova EE, Meerson FZ.

The effect of electroacupuncture on stress-induced drop in cardiac fibrillation threshold and catecholamine content in the adrenergic terminals of the myocardium was studied in Wistar rats. Transauricular electroacupuncture causing drowsiness in animals was found to prevent a drop in cardiac fibrillation and norepinephrine level in the adrenergic terminals usually observed after long immobilization stress. It is assumed that the preventive effect of acupuncture may be attributable to reflex activation of the inhibitory brain system which restricts stress reaction.

PMID: 3620666 [PubMed - indexed for MEDLINE]

Ugeskr Laeger. 2003 Apr 28;165(18):1868-71. Related Articles, Links

[Effect of Coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial]

[Article in Danish]

Engelsen J, Nielsen JD, Hansen KF.

Klinisk Biokemisk Afdeling, Koagulationslaboratoriet, Amtssygehuset i Gentofte, Niels Andersens Vej 165, DK-2900 Hellerup.

INTRODUCTION: A few case-stories claim that the anti-oxidant Coenzyme Q10 and possibly also Ginkgo biloba interact with warfarin treatment. A decreased response to warfarin in the Coenzyme Q10 cases and an increased response in the Ginkgo biloba case have been described. MATERIAL AND METHODS: Twenty-four outpatients on stable, long-term warfarin treatment were included in a randomised, double blind, placebo-controlled crossover trial. Coenzyme Q10 100 mg daily, Ginkgo-Biloba 100 mg daily and placebo were given in random order over treatment periods of four weeks, each followed by a two week wash out period. The international normalized ratio (INR) INR was kept between 2.0 and 4.0 by appropriate adjustment of the warfarin dosage. RESULTS: Fourteen women and ten men, median ages 64.5 years (33-79) were included. Three patients withdrew from the study for personal reasons. The INR was stable during all treatment periods. The geometric mean dosage of warfarin did not change during the treatment periods: Ginkgo biloba 36.7 mg/week (95% confidence interval: 29.2-46.0); CoQ10 36.5 mg/week (29.1-45.8); placebo 36.0 mg/week (28.6-45.1). CONCLUSION: The study indicated that Coenzyme Q10 and Ginkgo biloba do not influence the clinical effect of warfarin.

Publication Types:

Clinical Trial

Randomized Controlled Trial

PMID: 12772396 [PubMed - indexed for MEDLINE]

Neurol Res. 2000 Jul;22(5):517-21. Related Articles, Links

Protective effect of ginkgo extract on rat brain with transient middle cerebral artery occlusion.

Zhang WR, Hayashi T, Kitagawa H, Sasaki C, Sakai K, Warita H, Wang JM, Shiro Y, Uchida M, Abe K.

Department of Neurology, Okayama University Medical School, Japan.

It has been empirically known that Ginkgo extract is useful for reducing many symptoms associated with cerebral blood flow (CBF) insufficiency, but its mechanisms have been uncertain. In the present study, therefore, we gave Ginkgo extract to rats with per os digestion, and investigated its effect on CBF and ischemic brain damage with middle cerebral artery occlusion (MCAO). The treatment with Ginkgo extract (10 mg 100 g-1 rat) increased CBF in the normal condition, but the degree of increase in CBF was lesser during and after MCAO. TTC staining showed that infarct volume was reduced with Ginkgo treatment. TUNEL and HSP72 immunostaining confirmed the protective effect of Ginkgo treatment reducing numbers of TUNEL and HSP72 positive cells. Immunohistochemical analysis showed that caspase-3 expression was less abundant in Ginkgo treated rats. The present results suggest that Ginkgo extract contains a substance which increases normal CBF and reduces ischemic brain damage.

PMID: 10935227 [PubMed - indexed for MEDLINE]

Neurology. 2003 Nov 11;61(9):1273-5. Related Articles, Links

Dietary antioxidants and the risk of ischemic stroke: the Rotterdam Study.

Voko Z, Hollander M, Hofman A, Koudstaal PJ, Breteler MM.

Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands.

In the Rotterdam Study, the authors investigated whether high intake of antioxidants from food is associated with the risk of stroke. Among 5,197 participants who were followed on average for 6.4 years, 227 ischemic strokes occurred. Higher intake of antioxidants was associated with a lower risk of stroke. The relationship was dose-dependent, significant for vitamin C, and most pronounced in smokers. These results agree with the view that high dietary intake of antioxidants, in particular vitamin C and--in smokers--vitamin E, reduces the risk of stroke.

PMID: 14610137 [PubMed - indexed for MEDLINE] Stroke. 2003 Oct;34(10):2355-60. Epub 2003 Sep 18. Related Articles, Links

Vegetable and fruit intake and stroke mortality in the Hiroshima/Nagasaki Life Span Study.

Sauvaget C, Nagano J, Allen N, Kodama K.

Department of Epidemiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, 732-0815 Hiroshima, Japan.

BACKGROUND AND PURPOSE: Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately. METHODS: A prospective cohort study of 40 349 Japanese men and women was initiated in 1980-1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered. RESULTS: A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction. CONCLUSIONS: Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.

PMID: 14500940 [PubMed - indexed for MEDLINE]

Am J Clin Nutr. 2003 Jul;78(1):57-64. Related Articles, Links

Intake of fruit and vegetables and the risk of ischemic stroke in a cohort of Danish men and women.

Johnsen SP, Overvad K, Stripp C, Tjonneland A, Husted SE, Sorensen HT.

Department of Clinical Epidemiology, Aarhus University Hospital and Aalborg Hospital, Aarhus, Denmark.

BACKGROUND: Previous studies have suggested that a high dietary intake of fruit and vegetables is associated with a reduced risk of ischemic stroke. The magnitude of the effect is uncertain, and only one study reported data on the intake of specific fruit and vegetables and the risk of stroke. OBJECTIVE: We examined whether the intake of fruit and vegetables is associated with a reduced risk of ischemic stroke, with particular attention paid to specific fruit and vegetables and subtypes of ischemic stroke. DESIGN: In a prospective cohort study of 54,506 men and women who were included in the Danish Diet, Cancer, and Health study from 1993 to 1997, estimated total intakes of fruit and vegetables (in g/d) were extracted from a semiquantitative food-frequency questionnaire completed at baseline. Data about subjects hospitalized with ischemic stroke were obtained from the Danish National Registry of Patients and were verified later by record reviews. The follow-up for ischemic stroke ended on the date of a first hospital admission for stroke or transient ischemic attack, the date of death or emigration, or the end of the study, whichever came first. RESULTS: We identified 266 cases of ischemic stroke involving hospitalization during 168,388 person-years of follow-up (median follow-up: 3.09 y; range: 0.02-5.10 y). After adjustment for potential confounders, persons in the top quintile of fruit and vegetable intake (median: 673 g/d) had a risk ratio of ischemic stroke of 0.72 (95% CI: 0.47, 1.12) relative to persons in the bottom quintile of intake (median: 147 g/d) (P for trend = 0.04). When comparing the top quintile with the bottom quintile, an inverse association was most evident for fruit intake (risk ratio: 0.60; 95% CI: 0.38, 0.95; P for trend = 0.02). Similar risk estimates were seen for most types of fruit and vegetables, although the risks were significant only for citrus fruit. CONCLUSION: An increased intake of fruit may reduce the risk of ischemic stroke.

PMID: 12816771 [PubMed - indexed for MEDLINE]

Heart. 2011 Apr 8. [Epub ahead of print]

Prevention of atrial fibrillation with omega-3 fatty acids: a meta-analysis of randomised clinical trials.

Liu T, Korantzopoulos P, Shehata M, Li G, Wang X, Kaul S.

SourceCedars-Sinai Medical Center, Los Angeles, California, USA.


Context Previous randomised controlled trials (RCT) regarding n-3 PUFA supplementation for atrial fibrillation (AF) prevention have yielded conflicting results. Objective A systematic review and meta-analysis of RCT was conducted to examine the role of n-3 PUFA in AF prevention. Data Sources MEDLINE, Web of Science and Cochrane clinical trials database were searched until November 2010. Study Selection Of 127 initially identified studies, 10 RCT with 1955 patients were finally analysed. Data Extraction Two blinded reviewers extracted data independently to a predefined form. Disagreements were resolved through discussion and consensus. Results n-3 PUFA had no significant effect on the prevention of AF (OR 0.81, 95% CI 0.57 to 1.15; p=0.24). There was significant heterogeneity among the studies (p=0.002, I(2)=65.0%). Subgroup analysis showed no significant beneficial effect of fish oils in any subset of population. Conclusions No significant effects of n-3 PUFA supplementation on AF prevention were observed in this meta-analysis. A large-scale trial with higher doses and longer follow-up might be required to rule out the possibility of any treatment benefit.


Health Technol Assess. 2008 Jun;12(28):iii-iv, ix-95.

Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery bypass surgery: a systematic review and economic evaluation.

Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D, Price A.

SourceSouthampton Health Technology Assessments Centre, University of Southampton, UK.


OBJECTIVES: To assess the clinical and cost-effectiveness of magnesium sulphate compared with sotalol, and to assess the clinical effectiveness of magnesium sulphate compared with placebo in the prevention of atrial fibrillation (AF) in patients who have had a coronary artery bypass graft (CABG).

DATA SOURCES: Major electronic databases were searched from December 2003 to May 2007.

REVIEW METHODS: Selected studies were assessed, subjected to data extraction using a standard template and quality assessment using published criteria. A simple short-term economic model was developed, informed by a systematic review of economic evaluations and populated with data from a review of costing/resource-use studies and other published studies. The cost-effectiveness of magnesium sulphate as prophylaxis was estimated for a set of base-case assumptions and the robustness of these results was assessed using deterministic and probabilistic sensitivity analysis.

RESULTS: Twenty-two papers met the inclusion criteria reporting 15 trials which all compared magnesium sulphate with placebo or control. They ranged in size from 15 to 176 patients randomised, and were conducted in Europe, the USA and Canada. The standard of reporting was generally poor, with details of key methodological attributes difficult to elucidate. No trials were identified that specifically aimed to compare magnesium sulphate with sotalol. Of 1070 patients in the pooled magnesium group, 230 (21%) developed postoperative AF, compared with 307 of 1031 (30%) patients in the placebo or (control) group. Meta-analysis using a fixed-effects model generated a pooled odds ratio (OR) that was significantly less than 1.0 [OR=0.65, 95% confidence interval (CI) 0.53 to 0.79, test for overall effect p<0.0001], but with statistically significant heterogeneity (I2=63.4%, p=0.0005). Two randomised controlled trials (RCTs) were notable as they had relatively lower ORs in favour of magnesium sulphate. When these were removed from the analyses the pooled OR remained statistically significant, but heterogeneity no longer remained significant. These two studies tended to impart a highly significant reduction in the odds of AF to whichever subgroup they were analysed in. When studies were ordered by total duration of prophylaxis, an apparent relationship between duration and odds of AF was evident, with decreasing odds of AF as duration of prophylaxis increased. This was confirmed by linear regression analysis (R2=0.743, p<0.001). When the data were grouped into three classes according to duration, a statistically significant intervention effect was only present for the longest duration (OR=0.12, 95% CI 0.06 to 0.23, p=0.00001). Statistically significant intervention effects were associated with the initiation of prophylaxis 12 hours or more before surgery (OR 0.26; 95% CI 0.16 to 0.44, test for overall effect p=0.00001, fixed-effects model) and less than 12 hours before surgery or during the surgery itself (OR=0.73, 95% CI 0.56 to 0.97, test for overall effect p = 0.03, fixed-effects model), but not when prophylaxis was initiated at the end of surgery or postsurgery (OR=0.85, 95% CI 0.59 to 1.22, p=0.37, fixed-effects model). When studies were ordered by total dose of intravenous magnesium sulphate (<25 g), the odds of AF were independent of the dose. A notable exception was that for a total dose of 9 g magnesium sulphate; here the odds of AF were significantly reduced relative to the control group, although this may be explained by the fact that these studies had excluded patients who were on antiarrhythmic drugs and so may have been at higher risk of AF. Sixty-three potentially relevant references about cost-effectiveness were identified, but no economic evaluations of intravenous magnesium alone as prophylaxis against AF following CABG, compared with sotalol as prophylaxis or no prophylaxis, were identified. Studies reporting resource use by patients with AF following CABG suggest that while AF significantly increased inpatient stays, by up to 2.3 days in the intensive care unit (ICU) and 3.4 days on the ward, differences in length of stay and costs between patients receiving prophylaxis and those not receiving prophylaxis were not statistically significant. In the base-case analysis, magnesium sulphate prophylaxis resulted in 0.081 fewer cases of AF at an incremental cost of 2.55 pounds sterling. The incremental cost-effectiveness ratio (ICER) was 32 pounds sterling per AF case avoided. The estimated difference in average length of stay between the prophylaxis and no-prophylaxis strategies was only 0.24 days, despite a large assumed difference of 3 days for patients experiencing AF in each group (1 extra day in the ICU and 2 extra days on the ward). In a deterministic sensitivity analysis the greatest variation in ICERs was observed for input parameters relating to the baseline risk of AF following CABG and the effectiveness of prophylaxis, cost of prophylaxis and the resource consequences of postoperative AF. The largest ICER (2092 pounds sterling) in the sensitivity analysis was associated with increasing the length of patients' preoperative stay. In the base case it was assumed that admission routines would be identical under both strategies. However, patients receiving prophylaxis by intravenous infusion may have longer preoperative stays. In a probabilistic analysis the majority of the simulations were associated with improved outcomes (in this case fewer cases of AF), but also higher costs. Prophylaxis was the dominant strategy (better outcome at lower cost) in about 41% of the simulations using the base-case assumptions. Under an alternative scenario where patients receiving prophylaxis are admitted for longer before their operation, to receive their initial infusion, the proportion of simulations where prophylaxis dominates fell to around 5%. The probability of being cost-effective was 99% at a willingness to pay (WTP) threshold of 2000 pounds sterling per AF case avoided and 100% at a WTP threshold of 5000 pounds sterling per AF case avoided under the base-case assumptions. Under the alternative scenario of longer preoperative stays the probability of being cost-effective at these two threshold values fell to 48% and 93%, respectively. It is unclear what the appropriate decision threshold should be, given that this model used intermediate rather than final outcomes.

CONCLUSIONS: No RCTs were identified that specifically aimed to compare intravenous magnesium with sotalol as prophylaxis for AF in patients undergoing CABG. Intravenous magnesium, compared with placebo or control, is effective in preventing postoperative AF, as confirmed by a statistically significant intervention effect based on pooled analysis of 15 RCTs. It was also found that AF was less likely to occur when a longer duration of prophylaxis was used, and the earlier that prophylaxis is started; however, this finding was associated with two RCTs that had more favourable results than the other trials. No clear relationship between dose and AF was observed, although a lower constant dose rate was associated with the lowest odds of AF. Further research should investigate the relationship between dose, dose rate, duration of prophylaxis, timing of initiation of therapy and patient characteristics, such as degree of risk for AF. This will provide stronger evidence for the optimum delivery of intravenous magnesium in patients undergoing CABG. In the base-case analysis in the economic model, magnesium sulphate prophylaxis reduced the number of postoperative AF cases at a modest increase in cost. The results of the economic analysis are highly sensitive to variation in certain key parameters. Prophylaxis is less likely to be a cost-effective option if it requires changes in admission routines that result in longer preoperative stays than would be the case without prophylaxis.