hypertension
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Hypertension Linked to Disability in Older Adults

Reuters Health Information 2007. © 2007 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.

NEW YORK (Reuters Health) Dec 25 - Uncontrolled hypertension is associated with an increased risk of disability in older adults, according to a report in the December issue of Hypertension.

"Considering that 65% of the elderly population has hypertension and that 71% of them have uncontrolled hypertension, it is contributing significantly to disability and to healthcare expenditure in the US," lead author Dr. Ihab Hajjar and colleagues note.

Dr. Hajjar, from Harvard Medical School in Boston, and associates analyzed data from 999 stroke-free subjects who were enrolled in the Charleston Heart Study from 1960 to 1993. The average patient age was 68.5 years and 57% of subjects were female and 39% were African American.

Systolic and diastolic blood pressures were measured at multiple points throughout the study period. A variety of standard tests, such as the Rosow-Breslaw Scale, and Katz' Activities of Daily Living Scale, were used to assess function and disability during follow-up.

Increases in systolic, but not diastolic, blood pressure during the study were associated with reduced function on all of the tests.

The presence of hypertension (140/90 mm Hg or greater or the use of antihypertensive agents) raised the risk of new disability between 28% and 30%, depending on the test.

Uncontrolled hypertension (140/90 mmHg or greater while using antihypertensive agents) increased the risk by 29% to 35%.

With controlled hypertension, the risk for disability ranged from 16% to 25%, but this was not statistically significant.

"Identification of another risk factor for disability, in this case, hypertension, may be considered bad news," Drs. Merrill F. Elias and Penelope K. Elias, from the University of Maine in Orono, comment in a related editorial. "However, the study by Hajjar et al also offers good news. A successfully treated cohort of study participants for whom blood pressure was reduced to normal levels on antihypertensive drugs did not show decline in functional abilities compared with normotensive subjects."

Hypertension 2007;1006-1008,1026-1032.

vervolg Aablation (AF)
Catheter Ablation of Atrial Fibrillation: Do We Know What We are Doing?

Demosthenes G. Katritsis; A. John Camm

Europace. 2007;9(11):1002-1005. ©2007 Oxford University Press
Posted 12/17/2007
Introduction

Although atrial fibrillation (AF) represents the most common arrhythmia that is seen in every day cardiology practice,[1-3] the surgeons, and not the cardiologists, were the first to take the initiative for its radical cure. Cox and colleagues[4,5] developed the Maze procedure and its modifications in the 80s followed by the pioneering attempt of Swartz et al.[6] to ablate the arrhythmia in the electrophysiology laboratory in 1994. Now, catheter ablation is an established therapeutic option for certain patients with AF. Several ablation strategies have emerged which, although extremely diverse, report similar success rates, in the range of 60-80%, with 30-40% of patients followed for a year or two having had two procedures, however, different endpoints and methodology of assessment of AF recurrence make interpretation of success rather difficult.[7] It is of interest that despite the considerable clinical experience and accumulated evidence from experimental data, the exact mechanism of eliminating AF by catheter ablation techniques is still unknown.
Pulmonary Vein Isolation, Substrate Modification, or Both?

Since the seminal studies by Haissaguerre's group,[8] the effectiveness of segmental ablation at the ostia of the pulmonary veins (PV) has been demonstrated in several reports. There is substantial evidence that isolation of the PV, either by ostial or circumferential radiofrequency lesions, removes a potential source of arrhythmia that initiates and perpetuates AF. Although re-emergence of AF following PV disconnection procedures is usually due to recurrence of PV conduction,[9-11] complete electrical isolation of the PVs may not be necessary for a successful outcome.[10,12-16] Recurrence of PV conduction following complete PV isolation may occur in up to 98% of PVs and may not indicate a propensity to arrhythmia.[16] Thus, recurrence of AF following ablation indicates recurrence of PV conduction, but the opposite is not always true. Anatomically guided circumferential PV ablation even when performed with a clear endpoint of delivering coalescent lesions that produce a voltage reduction to <0.1 mV and delayed local conduction (>30 ms) between contiguous points across the line cannot achieve complete electrical isolation of PVs in 25-45% of patients.[11,17,18] When such clear endpoints are not necessarily achieved, complete isolation of all PVs is present in <20% of patients[14,19] and does not predict freedom from AF in the long-term.[19] Complete transmural lesions are difficult to obtain with percutaneous ablation techniques,[15,20-23] and achievement and verification of complete lines of block may be cumbersome. Nevertheless, the presence of anatomic gaps within linear ablation lesions does not necessarily preclude therapeutic effects.[21,24]

It seems that not only focal activity within the PVs may act as potential trigger of AF, but anisotropic conduction properties at the PV-left atrial junction may also promote reentry.[25] PV antral ablation, therefore, may be effective by modifying conduction properties of the PV-left atrial junction without achieving permanent PV isolation. Furthermore, nonencircling left atrial lesions created by catheter ablation have been found equally effective with circumferential ablation in eliminating permanent AF.[26] Intraoperative radiofrequency ablation noncircling lesions in the LA have been reported to have a success rate of 90% in the IRAAF study,[27] and surgical ablation of the left posterior atrial wall at the base of the left atrial appendage and at the orifice of the left inferior PV can terminate chronic AF.[28,29] High success rates have also been reported with tailored catheter approaches that target triggers and drivers of AF through spectral analysis and electrogram-guided ablation during AF or sinus rhythm[30-32] in the true atrium or the appendage, but the mechanism of eliminating AF appears to be different than that of circumferential ablation,[33] and success rates with electrogram-guided ablation have not always been so favourable.[34] Approaches aiming at non-inducibility of the arrhythmia may also produce favourable long-term results with[35,36] or without[36,37] verification of PV isolation. It seems, therefore, that conduction delay or substrate modification created by even incomplete ablation lines around the PV ostia may also prevent induction and/or maintenance of AF.
Aetiology of Atrial Fibrillation

These rather conflicting findings can be interpreted within the context of the multi-factorial aetiology of AF.[38] There is substantial evidence that, apart from PV firing, additional mechanisms may initiate and perpetuate AF. Other cardiac veins[39-41] and certain areas of the posterior left atrial wall[42-44] may have a profibrillatory role. Multiple re-entrant wavelets[45] and anisotropic reentry leading to rotors with a high dominant frequency[46,47] have been proposed as potential mechanisms of AF. Elimination of these rotors and AF nests may be one of the mechanisms for the efficacy of real-time frequency analysis or complex fractionated electrogram-guided ablation.[31,48]

Areas rich in sympathetic innervation may be the source of activity that triggers AF.[49,50] Ablation of the adjacent area of the ligament of Marshall has yielded moderate success in eliminating episodes of PAF.[51,52] Vagal reflexes from ganglionated plexi that can be identified by high-frequency stimulation at sites around the circumference of the left atrial-PV junction may also induce and perpetuate AF through spatial heterogeneity of refractoriness.[53,54] Damage to ganglionated plexi that are usually located 1-2 cm outside the PV ostia[55] has been proposed as a potential mechanism of antral PV ablation.[56,57] Partial vagal denervation by catheter ablation has been found efficacious in several studies,[54,58,59] and it seems that sympathetic stimulation may be much less effective than vagal stimulation in promoting AF. Parasympathetic denervation through epicardial fat pad ablation has also been reported to have a temporary only effect[60] or even to increase vulnerability of vagally mediated AF.[61] Of course, since both sympathetic and parasympathetic elements reside in all four major left atrial ganglionated plexi,[62,63] denervation lesions may unavoidably affect both components of the autonomic nervous system. Furthermore, nerve sprouting and sympathetic hyperinnervation may also occur early after catheter ablation.[64,65]

It seems that the more extensive the ablation-induced damage, the higher the possibility of intervening with these mechanisms. Pappone et al.[18] have suggested that the extent of left atrial ablation (average 30%) is a marker of success rather than PV isolation, although the addition of linear lesions to circumferential ablation by the same group did not affect recurrence rates of AF.[66] Mere elimination of the left atrial tissue below the critical amount required for reentry[67] may theoretically affect clinical outcomes. However, increased areas of scar with low voltage and slowed conduction in the left atrium following catheter ablation have also been identified as the underlying substrate for AF recurrence,[68] and atrial fibrosis may constitute a vulnerable substrate for AF.[69,70] Even the effect of ablation on left atrial transport function is debatable.[71-73] The increased risk of complications with extensive ablation procedures should be always kept in mind. According to real-life data, catheter ablation for AF is a procedure that carries a very small but not negligible risk for serious complications. In a recent worldwide survey on catheter ablation procedures for AF in clinical practice, the incidence of procedure-related stroke and mortality was 0.05 and 0.28%, respectively,[74] whereas in the recent report by the Hospital Corporation of America's Casemix Database, in-hospital mortality was 0.69%.[75]

It is not surprising, therefore, that for such a multi-factorial disease, no single ablation technique may be universally curative in the long-term. Indeed, true long-term efficacy data for these procedures is limited with most published studies having reported follow-up data for 6-12 months. In the worldwide survey,[74] follow-up varied widely from <6 months (20 centres), 7-12 months (29 centres), and 1-2 years (25 centres). Only 6 centese had follow-up data beyond 2 years. In patients with heart disease, in particular, long-term follow-up data following ablation for AF is virtually lacking.[76,77] However, this particular patient subset is of particular interest, especially after recent evidence suggesting that catheter ablation of AF and restoration of sinus rhythm might eventually result in improvement of left ventricular function.[77]

In conclusion, various ablation techniques are now used for the ablative treatment of AF with a similar long-term success rate. Still, however, the exact mechanism(s) of eliminating AF by catheter ablation techniques is not known. Current ablation techniques appear to target different mechanisms that all contribute to the genesis and perpetuation of AF. PV isolation or modification of PV-left atrial conduction, elimination of rotors and drivers of AF within the left atrial myocardium and autonomic denervation, and, perhaps, elimination of electrically active myocardium beyond a critical threshold appear to constitute potential antiarrhythmic effects of catheter ablation. Further experimental and clinical evidence is certainly needed for the elucidation of these important issues.

How Much Fish Is Enough?

Michael Miller, MD, FACC, FAHA

Medscape Family Medicine. 2007; ©2007 Medscape
Posted 12/19/2007

Question
Can't people get the omega-3 fatty acids they need from a diet rich in fish?

Response from Michael Miller, MD, FACC, FAHA
Associate Professor of Medicine, Epidemiology, and Preventive Medicine; Director, Center for Preventive Cardiology, Division of Cardiology, University of Maryland Medical Center, Baltimore, Maryland

The answer depends on the amount required for the potential cardiovascular benefits attributable to omega-3 fatty acids. Specifically, omega-3 fatty acids have been shown to reduce the risk of sudden cardiac death in patients with preexisting coronary heart disease (CHD)[1] and to lower triglyceride (TG) levels in subjects with hypertriglyceridemia.[2] To achieve the former, the American Heart Association recommends the equivalent of 1 gram of active omega-3 compounds (eicosapentaenoic [EPA] and docosahexaenoic acids [DHA]) ingested daily.[3] This amount can be obtained by consuming a 4-ounce serving of white albacore tuna, 2 to 3 ounces of salmon (pink or red), 2 ounces of herring, and 2 to 3 ounces of sardines daily. Alternatively, significantly higher quantities of shellfish would need to be consumed, including 8 or more ounces of crab, shrimp, and lobster daily.[3] For significant TG-lowering effects (20% reduction and greater), the amount of EPA/DHA required is considerably higher (ie, 2 to 4 grams daily) and exceedingly difficult to obtain unless a person consumes vast quantities of fish every day. Therefore, patients with CHD can get the omega-3 fatty acids needed from a diet rich in oily fish. Similarly, patients with TG levels in the borderline-elevated range (150-199 mg/dL) may reduce TG levels by approximately 10% with consumption of fish equivalent to 1 gram of EPA/DHA. However, with higher TG levels, and especially when levels exceed 500 mg/dL, a diet rich in fish is most likely to be insufficient for reducing TG levels to an acceptable range.

Supported by an independent educational grant from Reliant Pharmaceuticals

Demosthenes G. Katritsis; A. John Camm

Europace. 2007;9(11):1002-1005. ©2007 Oxford University Press
Posted 12/17/2007
Introduction

Although atrial fibrillation (AF) represents the most common arrhythmia that is seen in every day cardiology practice,[1-3] the surgeons, and not the cardiologists, were the first to take the initiative for its radical cure. Cox and colleagues[4,5] developed the Maze procedure and its modifications in the 80s followed by the pioneering attempt of Swartz et al.[6] to ablate the arrhythmia in the electrophysiology laboratory in 1994. Now, catheter ablation is an established therapeutic option for certain patients with AF. Several ablation strategies have emerged which, although extremely diverse, report similar success rates, in the range of 60-80%, with 30-40% of patients followed for a year or two having had two procedures, however, different endpoints and methodology of assessment of AF recurrence make interpretation of success rather difficult.[7] It is of interest that despite the considerable clinical experience and accumulated evidence from experimental data, the exact mechanism of eliminating AF by catheter ablation techniques is still unknown.
Pulmonary Vein Isolation, Substrate Modification, or Both?

Since the seminal studies by Haissaguerre's group,[8] the effectiveness of segmental ablation at the ostia of the pulmonary veins (PV) has been demonstrated in several reports. There is substantial evidence that isolation of the PV, either by ostial or circumferential radiofrequency lesions, removes a potential source of arrhythmia that initiates and perpetuates AF. Although re-emergence of AF following PV disconnection procedures is usually due to recurrence of PV conduction,[9-11] complete electrical isolation of the PVs may not be necessary for a successful outcome.[10,12-16] Recurrence of PV conduction following complete PV isolation may occur in up to 98% of PVs and may not indicate a propensity to arrhythmia.[16] Thus, recurrence of AF following ablation indicates recurrence of PV conduction, but the opposite is not always true. Anatomically guided circumferential PV ablation even when performed with a clear endpoint of delivering coalescent lesions that produce a voltage reduction to <0.1 mV and delayed local conduction (>30 ms) between contiguous points across the line cannot achieve complete electrical isolation of PVs in 25-45% of patients.[11,17,18] When such clear endpoints are not necessarily achieved, complete isolation of all PVs is present in <20% of patients[14,19] and does not predict freedom from AF in the long-term.[19] Complete transmural lesions are difficult to obtain with percutaneous ablation techniques,[15,20-23] and achievement and verification of complete lines of block may be cumbersome. Nevertheless, the presence of anatomic gaps within linear ablation lesions does not necessarily preclude therapeutic effects.[21,24]

It seems that not only focal activity within the PVs may act as potential trigger of AF, but anisotropic conduction properties at the PV-left atrial junction may also promote reentry.[25] PV antral ablation, therefore, may be effective by modifying conduction properties of the PV-left atrial junction without achieving permanent PV isolation. Furthermore, nonencircling left atrial lesions created by catheter ablation have been found equally effective with circumferential ablation in eliminating permanent AF.[26] Intraoperative radiofrequency ablation noncircling lesions in the LA have been reported to have a success rate of 90% in the IRAAF study,[27] and surgical ablation of the left posterior atrial wall at the base of the left atrial appendage and at the orifice of the left inferior PV can terminate chronic AF.[28,29] High success rates have also been reported with tailored catheter approaches that target triggers and drivers of AF through spectral analysis and electrogram-guided ablation during AF or sinus rhythm[30-32] in the true atrium or the appendage, but the mechanism of eliminating AF appears to be different than that of circumferential ablation,[33] and success rates with electrogram-guided ablation have not always been so favourable.[34] Approaches aiming at non-inducibility of the arrhythmia may also produce favourable long-term results with[35,36] or without[36,37] verification of PV isolation. It seems, therefore, that conduction delay or substrate modification created by even incomplete ablation lines around the PV ostia may also prevent induction and/or maintenance of AF.
Aetiology of Atrial Fibrillation

These rather conflicting findings can be interpreted within the context of the multi-factorial aetiology of AF.[38] There is substantial evidence that, apart from PV firing, additional mechanisms may initiate and perpetuate AF. Other cardiac veins[39-41] and certain areas of the posterior left atrial wall[42-44] may have a profibrillatory role. Multiple re-entrant wavelets[45] and anisotropic reentry leading to rotors with a high dominant frequency[46,47] have been proposed as potential mechanisms of AF. Elimination of these rotors and AF nests may be one of the mechanisms for the efficacy of real-time frequency analysis or complex fractionated electrogram-guided ablation.[31,48]

Areas rich in sympathetic innervation may be the source of activity that triggers AF.[49,50] Ablation of the adjacent area of the ligament of Marshall has yielded moderate success in eliminating episodes of PAF.[51,52] Vagal reflexes from ganglionated plexi that can be identified by high-frequency stimulation at sites around the circumference of the left atrial-PV junction may also induce and perpetuate AF through spatial heterogeneity of refractoriness.[53,54] Damage to ganglionated plexi that are usually located 1-2 cm outside the PV ostia[55] has been proposed as a potential mechanism of antral PV ablation.[56,57] Partial vagal denervation by catheter ablation has been found efficacious in several studies,[54,58,59] and it seems that sympathetic stimulation may be much less effective than vagal stimulation in promoting AF. Parasympathetic denervation through epicardial fat pad ablation has also been reported to have a temporary only effect[60] or even to increase vulnerability of vagally mediated AF.[61] Of course, since both sympathetic and parasympathetic elements reside in all four major left atrial ganglionated plexi,[62,63] denervation lesions may unavoidably affect both components of the autonomic nervous system. Furthermore, nerve sprouting and sympathetic hyperinnervation may also occur early after catheter ablation.[64,65]

It seems that the more extensive the ablation-induced damage, the higher the possibility of intervening with these mechanisms. Pappone et al.[18] have suggested that the extent of left atrial ablation (average 30%) is a marker of success rather than PV isolation, although the addition of linear lesions to circumferential ablation by the same group did not affect recurrence rates of AF.[66] Mere elimination of the left atrial tissue below the critical amount required for reentry[67] may theoretically affect clinical outcomes. However, increased areas of scar with low voltage and slowed conduction in the left atrium following catheter ablation have also been identified as the underlying substrate for AF recurrence,[68] and atrial fibrosis may constitute a vulnerable substrate for AF.[69,70] Even the effect of ablation on left atrial transport function is debatable.[71-73] The increased risk of complications with extensive ablation procedures should be always kept in mind. According to real-life data, catheter ablation for AF is a procedure that carries a very small but not negligible risk for serious complications. In a recent worldwide survey on catheter ablation procedures for AF in clinical practice, the incidence of procedure-related stroke and mortality was 0.05 and 0.28%, respectively,[74] whereas in the recent report by the Hospital Corporation of America's Casemix Database, in-hospital mortality was 0.69%.[75]

It is not surprising, therefore, that for such a multi-factorial disease, no single ablation technique may be universally curative in the long-term. Indeed, true long-term efficacy data for these procedures is limited with most published studies having reported follow-up data for 6-12 months. In the worldwide survey,[74] follow-up varied widely from <6 months (20 centres), 7-12 months (29 centres), and 1-2 years (25 centres). Only 6 centese had follow-up data beyond 2 years. In patients with heart disease, in particular, long-term follow-up data following ablation for AF is virtually lacking.[76,77] However, this particular patient subset is of particular interest, especially after recent evidence suggesting that catheter ablation of AF and restoration of sinus rhythm might eventually result in improvement of left ventricular function.[77]

In conclusion, various ablation techniques are now used for the ablative treatment of AF with a similar long-term success rate. Still, however, the exact mechanism(s) of eliminating AF by catheter ablation techniques is not known. Current ablation techniques appear to target different mechanisms that all contribute to the genesis and perpetuation of AF. PV isolation or modification of PV-left atrial conduction, elimination of rotors and drivers of AF within the left atrial myocardium and autonomic denervation, and, perhaps, elimination of electrically active myocardium beyond a critical threshold appear to constitute potential antiarrhythmic effects of catheter ablation. Further experimental and clinical evidence is certainly needed for the elucidation of these important issues.

J Goossens



Although atrial fibrillation (AF) represents the most common arrhythmia that is seen in every day cardiology practice,[1-3] the surgeons, and not the cardiologists, were the first to take the initiative for its radical cure. Cox and colleagues[4,5] developed the Maze procedure and its modifications in the 80s followed by the pioneering attempt of Swartz et al.[6] to ablate the arrhythmia in the electrophysiology laboratory in 1994. Now, catheter ablation is an established therapeutic option for certain patients with AF. Several ablation strategies have emerged which, although extremely diverse, report similar success rates, in the range of 60-80%, with 30-40% of patients followed for a year or two having had two procedures, however, different endpoints and methodology of assessment of AF recurrence make interpretation of success rather difficult.[7] It is of interest that despite the considerable clinical experience and accumulated evidence from experimental data, the exact mechanism of eliminating AF by catheter ablation techniques is still unknown.
Section 1 of 3
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In This Article
Introduction
References
From Medscape Family Medicine
Best Evidence Review
Warfarin vs Aspirin in Atrial Fibrillation -- New Perspectives: A Best Evidence Review CME/CE
Posted 12/20/2007
Charles P. Vega, MD
Disclosures
Introduction

Stroke is one of the most significant risks associated with atrial fibrillation, yet many patients with an indication for poststroke warfarin therapy do not receive this treatment. In part, this is because of uncertainty regarding the balance of risks and benefits of warfarin therapy, especially in high-risk populations. A recent meta-analysis and randomized trial provide new insights into this issue.
Best Evidence Reference

Oral Anticoagulants Versus Antiplatelet Therapy for Preventing Stroke in Patients With Non-Valvular Atrial Fibrillation and No History of Stroke or Transient Ischemic Attacks
Aguilar MI, Hart R, Pearce LA
Cochrane Database Syst Rev. 2007 Jul 18;3:CD006186
Available at: Abstract Accessed December 11, 2007.

Warfarin Versus Aspirin for Stroke Prevention in an Elderly Community Population With Atrial Fibrillation (The Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): A Randomised Controlled Trial
Mant J, Hobbs R, Fletcher K, et al
Lancet. 2007;370:493-503
Available at: Abstract Accessed December 11, 2007.

These studies were selected from Medscape Best Evidence, which uses the McMaster Online Rating of Evidence System. Of a possible top score of 7, the Cochrane study was ranked as 5 for newsworthiness and 7 for relevance by clinicians who used this system. The BAFTA study was ranked as 7 for newsworthiness and 7 for relevance.
Commentary

Approximately 2.2 million people in the United States have atrial fibrillation. It is a common problem that increases in prevalence as patients grow older -- from 2.3% among adults over age 40 to 5.9% among people older than 65 years, with the median age being 75. There does not appear to be a predilection based on gender, although the absolute number of women older than 75 with atrial fibrillation exceeds the number of men at those ages.[1]

Atrial fibrillation is the most common cause of cardioembolic stroke. The current meta-analysis suggests that the annual risk for stroke among patients with atrial fibrillation and no history of anticoagulation or prior cerebrovascular disease is between 2.5% and 4%.

A recent systematic review found that the risk for stroke in the setting of atrial fibrillation was most significantly elevated by a history of prior stroke or transient ischemic attack.[2] Other factors that increased the risk for stroke in patients with atrial fibrillation were advanced age and a history of hypertension or diabetes mellitus. However, female sex and a history of heart failure or coronary artery disease were not conclusively linked with an increased risk for stroke.

Current guidelines recommend warfarin adjusted to achieve an international normalized ratio (INR) between 2 and 3 to prevent stroke among patients with atrial fibrillation and a history of prior cerebrovascular disease, prosthetic heart valve, or mitral stenosis.[3] Warfarin therapy should also be considered for patients age 75 or over and those with hypertension, diabetes, heart failure, or a documented left ventricular ejection fraction of less than 35%. Other patients with atrial fibrillation may receive aspirin for stroke prevention.

There is evidence that many patients with atrial fibrillation do not receive their recommended treatment. In a study of 405 patients with atrial fibrillation, only 51% were discharged from the hospital with a prescription for warfarin, and fewer than half of patients over age 80 received warfarin.[4] This phenomenon may be in part the result of previous reviews of randomized controlled trials that questioned whether anticoagulation provides a significant clinical benefit compared with antiplatelet therapy for patients with atrial fibrillation. A meta-analysis of 5 studies of patients with nonrheumatic atrial fibrillation found no benefit of anticoagulation with warfarin vs all antiplatelet therapy in terms of overall mortality or death resulting from stroke.[5] The 32% reduction in the risk for nonfatal stroke in the warfarin vs antiplatelet treatment groups was of borderline statistical significance, and this result was not significant when a trial with weak methodology was excluded. Moreover, warfarin was associated with a nonsignificant 45% increase in the risk of major bleeding events vs antiplatelet therapy.

Another review that limited its meta-analysis to treatment with warfarin vs aspirin for patients with atrial fibrillation found a more robust protective effect against stroke with warfarin, which also produced superior results for all cardiovascular outcomes.[6] The difference is that the other meta-analysis examined all antiplatelet therapy, not just aspirin. However, warfarin also increased the risk of major bleeding vs aspirin, meaning that for every 1000 patients with atrial fibrillation treated with warfarin instead of aspirin, 23 additional ischemic strokes would be prevented at the cost of 9 additional cases of major bleeding.

The current meta-analysis of warfarin vs antiplatelet therapy includes data from 8 trials involving a total of 9598 patients with atrial fibrillation. Six trials used aspirin as the antiplatelet agent, and 1 trial used dual antiplatelet therapy with aspirin and clopidogrel. The dose of aspirin ranged between 75 mg and 325 mg daily. The minimal target INR for warfarin therapy was 1.5, and 6 trials reported that at least 50% of their study cohort achieved the target INR.

Treatment with warfarin reduced the risk of all strokes by 32% compared with antiplatelet therapy (P = .0007). This means that 13 additional strokes would be prevented by treating 1000 patients with warfarin instead of antiplatelet agents for 1 year. Warfarin also reduced the risk of ischemic stroke by nearly half compared with antiplatelet therapy.

Warfarin was not superior to antiplatelet therapy in terms of prevention of disabling or fatal strokes or vascular death. Overall rates of mortality were also similar between the 2 treatments. However, warfarin reduced the risk of myocardial infarction by 31% compared with antiplatelet therapy (P = .06). There were 41 intracranial hemorrhages reported during the trials, and warfarin increased the risk of hemorrhage by 98% compared with antiplatelet treatment.

Although older adults bear the greatest risk for stroke in atrial fibrillation, the choice for stroke prevention in this important patient group has not been as scrutinized as it has among younger patients. The authors of the Birmingham Atrial Fibrillation Treatment of the Aged Study (BAFTA) note that the average age in previous studies of stroke prevention among patients with atrial fibrillation is 69 years. Therefore, they compared warfarin and aspirin therapy among patients age 75 or older.

The trial recruited patients from 260 general practices in England and Wales. A total of 973 patients with atrial fibrillation and no risk factors for major bleeding were randomized in an open-label design to receive either aspirin 75 mg daily or warfarin; the target INR range was 2 to 3. The primary study outcome was the combined rate of stroke, intracranial hemorrhage, and clinically significant arterial embolism.

The average age of study subjects was 81.5 years, and 20% of participants were at least 85 years old. There was a history of stroke or transient ischemic attack in 12% of participants, and similar proportions of patients in the 2 treatment groups were receiving aspirin or warfarin at baseline.

The average follow-up time for study outcomes was 2.7 years. One third of patients randomized to receive warfarin stopped taking it, and the remaining patients were in the target INR range two thirds of the time. The use of blood pressure and lipid-lowering medications was similar between treatment groups.

Warfarin reduced the rate of the combined primary outcome by 52% compared with aspirin. Warfarin was as effective in the primary outcome among patients at age 85 or older as it was in younger patients and was also more effective when examining patient subgroups based on gender, previous history of stroke, or baseline risk of stroke. At the same time, warfarin was not more effective than aspirin in the prevention of nonstroke vascular events or overall mortality rates.

A surprising finding was that there was no significant increase in the risk of major hemorrhage with warfarin vs aspirin therapy. However, the confidence intervals in this finding were wide, suggesting that a larger patient cohort or greater adherence to randomized therapy could have demonstrated a significant difference between treatments. The researchers also note that their target INR was lower than in previous studies, which could also account for lower rates of hemorrhage among participants receiving warfarin.

Reducing the risk of stroke is one of the most important aspects of caring for patients with atrial fibrillation, and improvements in therapy beyond anticoagulation or antiplatelet therapy may have lessened the risk for stroke over the last decade. In BAFTA, the annual rate of stroke among patients with at least a moderate baseline risk was 3.3%, which compared favorably with a predicted rate of 9.9% based on previous reports. In addition, a recent trial of clopidogrel plus aspirin vs warfarin for stroke prevention among patients with atrial fibrillation and at least 1 other risk factor for stroke also found a lower than expected rate of vascular events, with an annual rate of stroke of 3.93% in the warfarin arm of the trial.[7] This trial was stopped early because of the apparent superiority of warfarin compared with aspirin plus clopidogrel in vascular outcomes.

Whereas the risk of stroke and vascular events among patients with atrial fibrillation may be decreasing, the risk of mortality among patients with this condition appears to be stagnant. In a study that followed a cohort of patients with atrial fibrillation in a Minnesota community, the risk of mortality was essentially unchanged between 1980 and 2000.[8] During the first 4 months after diagnosis with atrial fibrillation, the mean hazard ratio of overall mortality was 9.62 when comparing patients with atrial fibrillation vs age- and gender-matched control subjects without atrial fibrillation, and this risk fell to 1.66 thereafter.

Could greater adherence to recommendations for warfarin therapy in atrial fibrillation improve the rate of mortality associated with this condition? The current articles do not find a direct mortality benefit of warfarin vs antiplatelet treatment, but it would be reasonable to believe that greater adherence to guidelines among thousands of patients could reduce not only the rate of stroke in atrial fibrillation, but also the death rate. Physicians should consider this possibility when evaluating patients with atrial fibrillation.

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