Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Anticoagulant therapy for atrial fibrillation Joel K. Kahn MD To cite this article: Joel K. Kahn MD (1992) Anticoagulant therapy for atrial fibrillation, Postgraduate Medicine, 92:3, 119-130, DOI: 10.1080/00325481.1992.11701444 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701444
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [Monash University Library]
Date: 10 June 2016, At: 16:58
-@CME credit article
Anticoagulant therapy for atrial fibrillation Recommendations from major studies
Joel K. Kahn, MD
Downloaded by [Monash University Library] at 16:58 10 June 2016
Preview When should anticoagulants be used in patients with atrial fibrillation? Which patients should receive aspirin alone? What risk factors exclude patients from such management? Dr Kahn examines the results of four recent studies and discusses the appropriate application of anticoagulant therapy in clinical practice.
Atrial fibrillation affects 2% of the general population and 5% of persons older than 60 years of age. 1 Two aspects of the disorder demand clinical attention: (1) the rapid ventricular rate in patients with new-onset atrial fibrillation and (2) the long-term risk of thromboembolic events. In patients with new-onset atrial fibrillation, a rapid ventricular rate response may lead to breathlessness, chest discomfon, light-headedness, or even syncope. Early treatment therefore focuses on control of the ventricular rate with agents that slow conduction through the atrioventricular node, such as digoxin (Lanoxicaps, Lanoxin), beta blockers, and calcium blockers. Cardioversion also may be required if hemodynamic instability is caused by the rapid ventricular rate. Reducing the long-term risk of thromboembolic events, predominantly cerebrovascular accidents, is a major challenge to physicians caring for patients with atrial fi-
brillation. Indeed, atrial fibrillation is the most common cardiac disorder predisposing to systemic embolism. 1 Until recently, decisions regarding the use of anticoagulants in patients with atrial fibrillation were largely empirical and limited to those with mitral stenosis. Now, however, several recent studies have provided insight into the use of anticoagulants in a broader range of patients. These are reviewed with an emphasis on practical implications for management in clinical practice.
Chronic atrial fibrillation Over the years, rheumatic valvular disease has often been accompanied by chronic atrial fibrillation. From 40% to 80% of patients who require surgery for symptomatic rheumatic valvular disease have chronic atrial fibrillation. Funhermore, in the Framingham Hean Study, it was found that the risk of stroke in patients with rheumatic hean disease and atrial fibrillation was eighteenfold
higher than the risk in controls. 2 A number of largely retrospective studies of the role of chronic anticoagulation in patients with rheumatic atrial fibrillation collectively demonstrated a reduction in the occurrence of systemic emboli, pulmonary emboli, and death in patients who received anticoagulants. 1 It has become common practice to prescribe warfarin sodium (Coumadin, Panwarfin, Sofarin) in patients with rheumatic valvular disease complicated by atrial fibrillation, although the value of long-term anticoagulant therapy has never been confirmed in a well-designed prospective trial. 1 In patients with an absolute contraindication to warfarin therapy, daily aspirin therapy may serve as an alternative. In the Framingham Hean Study, it was noted that the risk of stroke was sixfold higher in patients with nonrheumatic atrial fibrillation than in controls. Until several recent randomized trials were completed, however, the proper role of anticoagulant therapy in patients who have atrial fibrillation associated with such conditions as hypenension, coronary anery disease, and cardiomyopathy was uncenain. Indeed, a consensus panel reviewing the world literature in 1989 concluded that the data were inconclu-
continued
VOL 92/NO 3/SEPTEMBER 1. 1992/POSTGRADUATE MEDICINE • ATRIAL I'IBRILLAnGN
119
Downloaded by [Monash University Library] at 16:58 10 June 2016
Investigators in the AFASAK Study concluded that 75 mg of aspirin daily was ineffective in reducing the incidence of thromboembolic events in patients with atrial fibrillation.
sive regarding the routine use of anticoagulants in patients with nonrheumatic atrial fibrillation. 1 Fortunately, the results of four recent, large randomized trials investigating the role of long-term anticoagulant therapy in nonrheumatic chronic atrial fibrillation have been published and they provide a basis on which to make clinical recommendations. The studies include the Copenhagen Atrial Fibrillation, Aspirin, Anticoagulation (AFASAK) Study, Stroke Prevention in Atrial Fibrillation (SPAF) Study, Boston Area Anticoagulation Trial for Atrial Fibrillation (BMTAF), and Canadian Atrial Fibrillation Anticoagulation (CAFA) Study (see box on page 122).
Study results with warfarin The AFASAK Study was stopped prematurely because of a significant reduction in the incidence of thromboembolic events in patients treated with warfarin. During the study, 4 cerebral infarctions and 1 intracerebral hemorrhage occurred in the warfarin group (2% a year) compared with 21 events in the control group (5% a year). Only 1 Joel K. Kahn, MD Dr Kahn is a consulting cardiologist to the Michigan Heart and Vascular Institute, St Joseph Mercy Hospital, Ann Arbor.
120
withdrew from therapy. of the cerebral infarctions in the The CAFA Study was termiwarfarin group occurred during adequate anticoagulation. Also, nated prematurely. At the point of termination, an intention-toduring the study period, 38% of treat analysis identified 11 pripatients assigned to the warfarin group discontinued therapy. Half mary events in the control group (4.6% a year) compared with of these patients refused to con8 in the warfarin group (3.4% a tinue; side effects and noncomyear). During the study, 26% of pliance were additional common patients on warfarin withdrew reasons for withdrawal. from treatment. In the SPAF Study, randomMajor complications due to ization to the placebo arm was chronic anticoagulation were also terminated prematurely. At the time of termination, 6 strokes tracked in all four of the major had occurred in the warfarin trials (table 1). Because of careful monitoring of warfarin therapy group (2% a year) compared with 18 events (17 strokes, 1 sysand the low doses used, major temic embolism) in the control and fatal bleeding complications group (7% a year). In only 2 of were infrequent. Mi?or bleeding the 6 patients who had a stroke was more common m groups asin the warfarin group was antisigned to warfarin, despite strincogulation adequate at the time gent selection criteria. of the stroke. During the trial, 11% of warfarin patients withStudy results with aspirin drew from therapy. This was In two of the trials, AFASAK and most commonly due to poor SPAF, patients were randomized compliance, secondary events, or to either aspirin or placebo. In exclusion criteria such as angiothe AFASAK Study, 21 primary plasty, bypass surgery, or venous events were identified in placebothrombosis. treated patients and 20 events in BMTAF was completed with aspirin-treated patients, and the 212 patients in the warfarin investigators therefore concluded group and 208 in the control that 75 mg of aspirin daily was group. At completion, there had ineffective in reducing the incibeen 2 strokes in the warfarin dence of thromboembolic events. group (0.4% a year) compared In contrast, during the SPAF with 13 in the placebo group Study, 46 primary events oc(3% a year). During the study, curred in the placebo arm (6% a only 10% of warfarin patients year) compared with 26 events in
ATRIAL FIBRILLATION • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRAOUATE MEDICINE
Downloaded by [Monash University Library] at 16:58 10 June 2016
Systemic embolism is the most serious potential complication of cardioversion in patients with atrial fibrillation.
the aspirin group (4% a year), a significant reduction. A subgroup analysis indicated that all of the benefits from aspirin occurred in patients younger than 75. In patients older than 75, the yearly rate of stroke was identical in the aspirin and placebo groups (7.4% a year), whereas in patients 75 or younger the rate was 6.2% a year in the placebo arm compared with 2.2% a year in the aspirin arm. 3 Patients in BAATAF were not randomized to aspirin therapy, but the number of patients in the placebo group who took aspirin was logged. Of the 13 strokes in the control group, 8 occurred in patients taking aspirin; thus there appeared to be no reduction in the incidence of stroke among control patients taking aspirin.
Acute-onset atrial fibrillation In the four trials reviewed here, the role of long-term anticoagulation in patients with predominantly chronic atrial fibrillation (and, less frequently, recurrent paroxysmal atrial fibrillation) was examined. Not reviewed was the role of immediate intravenous anticoagulation with heparin in patients presenting to the hospital or office with new-onset atrial fibrillation. The most often repeated clinical teaching has been that anticoagulation is unnecessary in patients who have acute
atrial fibrillation of less than 1 week's duration, even if cardiaversion is performed. 4 An alternative premise has been that patients with acute atrial fibrillation ofless than 3 days' duration do not require anticoagulation even if cardioversion is performed. 5 A recent consensus panel indicated that antithrombotic therapy is not necessary for atrial fibrillation of less than 2 days' duration, but the panel also acknowledged the lack of controlled data to guide therapy in such cases.' At present, there are no data to indicate that intravenous anticoagulants need to be initiated for new-onset atrial fibrillation on the day of admission. Prospective studies, however, are needed to determine whether the costs and bleeding risk accompanying routine early intravenous anticoagulation in patients presenting with newonset atrial fibrillation is justified by a reduction in clinical thromboembolic events. Although it is usually possible to estimate the duration of newly diagnosed atrial fibrillation by a carefully taken history that determines the time of onset of dyspnea, chest pain, or palpitations, occasionally the time cannot be definitely ascertained. In such instances, it is probably most appropriate to assume that the
arrhythmia is chronic and to institute anticoagulation with warfarin, if possible.
Elective cardioversion Management of patients with atrial fibrillation often involves attempts at restoring sinus rhythm through pharmacologic or electrical cardioversion. Systemic embolism is the most serious potential complication of cardioversion. There is not a single randomized prospective study of the role of anticoagulant therapy in reducing embolic events due to cardioversion. This issue has been examined in numerous retrospective clinical reports, however, and recommendations have been made regarding the use of anticoagulants in patients scheduled for cardioversion.'·6 It is generally recommended that patients with chronic atrial fibrillation be given warfarin for 3 to 4 weeks before scheduled cardioversion and for 3 to 4 weeks after the attempt if it is successful. No data suggest that pharmacologic cardioversion is any less likely than electrical cardioversion to cause systemic embolism, and several weeks of anticoagulation should probably precede pharmacologic cardioversion attempts, even when agents such as quinidine and procainamide hydrochloride (Pronestyl)
continued
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • ATRIAL FIBRILLAnGN
121
Downloaded by [Monash University Library] at 16:58 10 June 2016
Four major trials have consistently demonstrated a statistically and clinically important reduction in the incidence of strokes and systemic emboli in patients treated with low-dose warfarin therapy.
Study design and patient recruitment for recent studies on anticoagulant therapy for nonrheurnatic atrial fibrillation
Copenhagen Atrial Fibrillation, Aspirin, Anticoagulation (AFASAK) Study This was the first randomized, prospective evaluation of antithrombotic therapy for nonrheumatic atrial fibrillation. 1 It took place between 1985 and 1988 in a single center and had an enrollment of 1,007 patients with chronic atrial fibrillation. There was no upper age limit. Patients with thyroid disease constituted 5% of the group. Patients were randomized to receive either warfarin sodium, 75 mg of aspirin daily, or placebo. Warfarin was given openly, but aspirin and placebo were given in a double-blind manner. The warfarin dosage was adjusted for a prothrombin time {PT) ratio of 1.5 to 2.0 compared with control. The primary end point was a thromboembolic complication (transient ischemic attack, stroke, or embolism to the viscera or extremities). The secondary end point was death. Bleeding complications were classified as minor, major {requiring medical therapy), or fatal. The analysis was based on actual therapy received. Initial plans called for enrollment of 2,000 patients who were to be observed for 2 years, but the trial was terminated when an interim analysis identified a trend favoring the warfarin arm.
patients were excluded from consideration for the trial, most often because of inability to give informed consent, the presence of prosthetic heart valves, life expectancy that was less than 24 months, or transient, self-limited atrial fibrillation. There were 1,330 eligible and consenting patients. A subgroup of 627 patients were considered suitable for anticoagulant therapy with warfarin and were randomly assigned to either warfarin, 325 mg of aspirin daily, or placebo. The 703 eligible patients who were not candidates for anticoagulant therapy were randomized separately to aspirin or placebo. Patients younger than age 50 with lone atrial fibrillation were not randomized to warfarin therapy because the risk of stroke in this subgroup was believed to be too low to justify it. APT ratio of 1.3 to 1.8 was targeted for patients treated with warfarin. Intermittent atrial fibrillation was present in 34% of patients. Patients with thyroid disease and severe heart failure and mitral regurgitation were excluded. Primary end points assessed were ischemic strokes and systemic embolic events. Secondary end points were death, myocardial infarction, transient ischemic attacks, and unstable angina pectoris. The study design called for 1,644 patients to be observed for 3 years, but the study was stopped after the 1,330 patients were enrolled for a mean of 1.3 years of follow-up because a monitoring committee identified advantages in the antithrombotic arms. An intention-to-treat analysis was used.
Stroke Prevention in Atrial Fibrillation (SPAF) Study This trial took place between 1987 and 1989 in 15 centers across the United States. 2 A total of 17,046
Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) This randomized trial assessed the efficacy of lowdose warfarin therapy for nonrheumatic atrial fibril-
The following four major studies, now completed, were designed to investigate the role oflong-term anticoagulant therapy in patients who have nonrheumatic atrial fibrillation.
122
ATRIAL FIBRILLAnON • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE
Downloaded by [Monash University Library] at 16:58 10 June 2016
BAATAF was interrupted prematurely because of strong evidence favoring use of warfarin for anticoagulation therapy in patients with nonrheumatic atrial fibrillation.
!arion. It rook place between 1987 and 1990 in 32 centers in the northeastern United Srares. 3 Patients with chronic and intermittent atrial fibrillation were included; 17% of study patients had intermittent atrial fibrillation. Patients with severe congestive heart failure and hyperthyroidism were excluded. The number of patients screened for enrollment was nor reported. Patients were assigned to receive either warfarin therapy or placebo. Neither the patients nor their physicians were blinded to the assigned therapy. To give the study an 80% power to detect a reduction in the yearly rare of stroke from 5 per 100 patientyears to 1 per 100 patient-years, 400 patients were recruited to be followed for an average of 4.1 years. An intention-to-treat analysis was used. The warfarin group had dosages adjusted to PT ratios of 1.2 to 1. 5, the lowest of the four trials described here. Patients randomly assigned to the placebo group were permitted to take aspirin, and 46% of all patient-years in the placebo group represented participants taking aspirin. The primary end points were ischemic stroke and peripheral systemic thromboembolism. Major bleeding was defined as intracranial bleeding, fatal bleeding, or bleeding requiring transfusion of 4 or more units of blood within 48 hours. The study was interrupted prematurely by the monitoring committee after evidence favoring use of warfarin was judged strong enough to end the trial.
Canadian Atrial Fibrillation Anticoagulation (CAFA) Study This randomized, double-blind, placebo-controlled trial rook place between 1985 and 1989 in 11 Canadian centers.• Recruitment of 630 patients was
originally planned, bur the study was stopped when positive results of rhe AFASAK and SPAF studies were published.1.2 The mean follow-up of the 383 patients enrolled at that point was IS months. Patients with paroxysmal or chronic atrial fibrillation were included. Patients with hyperthyroidism were excluded bur those with severe congestive heart failure were randomized to therapy. During 8 months of the trial, derailed records indicated that only 6% of patients screened for the trial were randomized. Assignment to warfarin therapy to achieve a PT ratio of 1.3 to 1.6 was blinded from the patient and investigators by providing sham PT results for placebo patients. The primary end points were ischemic stroke, other systemic emboli, and intracranial or fatal hemorrhage. Secondary end points were myocardial infarction, death, major bleeding, minor bleeding, or transient ischemic attacks. An efficacy analysis that excluded events occurring more than 28 days after discontinuation of therapy was the primary analysis; an intention-to-treat analysis was secondary. References 1. Petersen P, Boysen G, Godtfred.sen J, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAKstudy. Lancet 1989;1{8631):175-9 2. Stroke Prevention in Atrial Fibrillation Investigators. Stroke Prevention in Atrial Fibrillation Study: final results. Circulation 1991; 84(2):527-39 3. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Eng! J Med 1990; 323(22): 1505-11 4. Connolly SJ, Laupacis A, Gent M, et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. JAm Coil Cardiol1991;18(2): 349-55
VOL 92/NO 3/SEPTEMBER 1. 1992/POSTGRADUATE MEDICINE • ATRIAL FIBRILLAnON
123
Downloaded by [Monash University Library] at 16:58 10 June 2016
Many patients with nonrheumatic atrial fibrillation are not eligible for long-term warfarin therapy.
Table 1. Hemorrhagic complications of long-term anticoagulation therapy with warfarin for nonrheumatic atrial fibrillation in four major studies Intracerebral hemorrhage Warfarin Control
AFASAK
0
SPAF
0
BMTAF
0
CAFA
0
Major bleeding
Warfarin
3
4
Minor bleeding
Control
Warfarin
0
21
4
4
2
Control 0
38
21
37
28
AFASAK, Copenhagen Atrial Fibrillation, Aspirin, Anticoagulation Study; BAATAF, Boston Area Anticoagulation Trial for Atrial Fibrillation; CAFA, Canadian Atrial Fibrillation Anticoagulation Study; SPAF, Stroke Prevention in Atrial Fibrillation Study.
Table 2. High- and low-risk factors for thromboembolic complications in patients with atrial fibrillation High-risk factors Rheumatic valve disease Advanced age Severe congestive heart failure Ventricular aneurysm Previous emboli Previous myocardial infarction lntracardiac thrombus Low-risk factors Lone atrial fibrillation Paroxysmal atrial fibrillation
124
are used. An exception would be in patients with new-onset atrial fibrillation ofless than 2 to 7 days' duration, as has been discussed.
Discussion The four randomized trials of anticoagulant therapy in patients with nonrheumatic atrial fibrillation collectively clarify recommendations for management of these patients in clinical practice. Even after excluding many groups of patients believed to be at high risk for thromboembolic complications of atrial fibrillation (table 2), the yearly risk of stroke or systemic embolism in patients with nonrheumatic atrial fibrillation
was 5% to 7% a year in the trials. Many of these events were disabling or fatal. The trials were consistent in demonstrating a statistically and clinically imponant reduction in the incidence of strokes and systemic emboli in patients who were treated long-term with low-dose warfarin therapy; this reduction was accomplished in exchange for a small bleeding risk. It has been estimated from the SPAF Study that for 1,000 patients similar to those enrolled in the warfarin study arm, 51 fewer strokes or systemic emboli (26 of which might have been severely disabling or fatal) could be anticipated as a result of longterm anticoagulant therapy in exchange for 4 bleeding events with residua. 7 The risk-benefit ratio is clearly in favor of low-dose warfarin therapy. Therefore, in addition to patients with rheumatic atrial fibrillation and those with prosthetic hean valves associated with atrial fibrillation, patients with nonrheumatic atrial fibrillation should be routinely treated with long-term warfarin therapy if there are no contraindications (table 3). Several additional lessons of clinical imponance can be derived from these recent trials. One is that many patients with nonrheumatic atrial fibrillation continued on page 129
ATRIAL FIBRILLATION • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE
Downloaded by [Monash University Library] at 16:58 10 June 2016
Continued encouragement and reinforcement regarding the importance of anticoagulation therapy are necessary to maintain patient commitment.
are not eligible for long-term warfarin therapy. Over 90% of patients screened for two of the trials were excluded. While many of these exclusions were for administrative reasons or because of a preexisting requirement for antithrombotic therapy, patients believed to be at high risk for bleeding from warfarin therapy were carefully excluded from all of the trials. Reproducing the overall favorable results of the trials in general clinical practice will therefore require similar careful selection of patients. A second lesson from the trials arises from the fact that many patients thought to be at highest risk for thromboembolic complications were excluded from the studies because withholding warfarin was considered inappropriate. Therefore, even though the advantages of warfarin therapy were not examined in patients who had atrial fibrillation with severe congestive heart failure, severe mitral regurgitation, recent embolic episodes, recent myocardial infarction, dilated cardiomyopathies, or prosthetic heart valves, such patients should be given anticoagulant therapy unless a major contraindication exists. Another observation from the studies relevant to clinical practice is that one tenth to one third
of patients withdrew from therapy, most commonly because of the inconvenience of frequent trips for prothrombin time measurements. Continued encouragement and reinforcement regarding the imponance of therapy are necessary to maintain patient commitment. Several questions remain unresolved by these trials. One is the proper role of aspirin in reducing the incidence of thromboembolic events. The conclusions of the AFASAK and SPAF studies were in opposition regarding the efficacy of aspirin, although statistically the findings in these two trials do overlap. 8 One obvious conclusion is that 75 mg of aspirin daily may be inadequate to prevent embolic events; a higher daily dosage of 325 mg (as used in the SPAF Study) should therefore be prescribed in clinical practice. A second conclusion is that aspirin may be less effective in patients over 75 years old, as was observed in the SPAF Study. The mean age of patients in the AFASAK Study (74) was higher than that in the SPAF Study (67), and this may have resulted in less impressive results. There is no direct comparison of aspirin and warfarin therapy available at this writing, although several trials, including a SPAF II study, are in progress and are
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • ATRIAL FIBRILLATION
Table 3. Risk factors for excessive bleeding with longterm anticoagulant therapy
Known bleeding disorder Previous hemorrhage with anticoagulant therapy Active peptic ulcer disease Alcoholism Uncontrolled hypertension Gait disorders or frequent syncope Severe renal or hepatic diseases Recent stroke
comparing the efficacy of these two agents. For now, it would appear that patients with nonrheumatic atrial fibrillation who are ineligible for warfarin therapy should be treated with 325 mg of aspirin daily, if at all possible. Whether this approach also benefits the very elderly needs to be clarified in ongoing studies. Two other patient groups deserve mention. First, patients younger than 50 to 60 years old who have atrial fibrillation and no evidence of structural heart disease (lone atrial fibrillation) are at very low risk for thromboembolic events.9 These patients continued
129
Downloaded by [Monash University Library] at 16:58 10 June 2016
Young patients who have paroxysmal atrial fibrillation without structural heart disease probably should be treated with aspirin alone.
Summary were excluded from the SPAF Study and were infrequent particThe role of antithrombotic ipants in the other studies. Until further information is available, therapy in reducing thromboembolic complications in pathey probably should be treated tients with chronic atrial fibrilwith daily aspirin therapy only. lation has been clarified by the The second group of patients includes those with paroxysmal results of four major randomatrial fibrillation. These patients ized and placebo-controlled were excluded from the AFASAK trials. Patients with rheumatic Study but accounted for about heart disease complicated by 10% to 30% of patients in the atrial fibrillation should receive other three trials. Although the long-term warfarin therapy to trials do not provide any definite reduce the risk of stroke unless guidelines, these patients have an absolute contraindication been found to have a consistently exists. Patients with nonrheulower risk of stroke in studies that matic atrial fibrillation should have compared paroxysmal with also be treated with low-dose chronic atrial fibrillation. 8 Young warfarin therapy, especially if patients who have paroxysmal high-risk features for thromboatrial fibrillation without strucembolism exist. In patients who tural heart disease probably should be treated with aspirin alone, whereas older patients or those with structural heart disease References should be treated with low-dose 1. Dunn M, Alexander J, de Silva R, et al. warfarin, if at all possible. Antithrombotic therapy in atrial fibrillation. Chest 1989;95(2 Suppl):118-27S Because of the short period of 2. Kannel WB, Abbott RD, Savage DD, et observation in the randomized al. Epidemiologic features of chronic atrial fitrials, additional follow-up of the brillation: the Framingham study. N Eng! J Med 1982;306(17):1018-22 participants is necessary to assess 3. Stroke Prevention in Atrial Fibrillation Inthe optimal duration of therapy vestigators. Preliminary report of the Stroke with antithrombotic agents. It Prevention in Atrial Fibrillation Study. N Eng! J Med 1990;322(12):863-8 would seem prudent to continue 4. DeSilva RA, Graboys TB, Podrid PJ, et al. antithrombotic therapy indefiCardioversion and defibrillation. Am Heart J nitely in patients with chronic 1980;100(6 Pt 1):881-95 5. Bjerkelund CJ, Orning OM. The efficacy of atrial fibrillation unless a new anticoagulant therapy in preventing embolism contraindication or a bleeding related to D.C. electrical conversion of atrial ficomplication occurs. brillation. Am J Cartliol 1969;23(2):208-16
130
have contraindications to warfarin therapy and in young patients with lone atrial fibrillation or paroxysmal atrial fibrillation, therapy with 325 mg of aspirin a day is preferred. Ongoing trials directly comparing aspirin and warfarin will provide additional insight into the optimal role of these antithrombotic agents in patients with atrial fibrillation. Rl't'l
-®
Earn credit on this article. See CME Qui,,
Address for correspondence: Joel K Kahn, MD, 5333 McAuley Dr, Suite 3009, Ann Arbor, MI 48106.
6. Stein B, Halperin JL, Fuster V. Should patients with atrial fibrillation be anticoagulated prior to and chronically following cartlioversion? In: Cheiclin MD, ed. Dilemmas in clinical cardiology. Vol21. Philadelphia: FA Davis, 1990: 231-49 7. Cairns JA. Stroke prevention in atrial fibrillation trial. (Etlitorial) Circulation 1991;84(2): 933-5 8. Cairns JA, Connolly SJ. Nonrheumatic atrial fibrillation: risk of stroke and role of antithrombotic therapy. Circulation 1991; 84(2):469-81 9. Kopecky SL, Gersh BJ, McGoon MD, et al. The natural history oflone atrial fibrillation: a population-based study over three decades. N Eng! J Med 1987;317(11):669-74
ATRIAL FIBRILLATION • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Anticoagulant therapy for atrial fibrillation Joel K. Kahn MD To cite this article: Joel K. Kahn MD (1992) Anticoagulant therapy for atrial fibrillation, Postgraduate Medicine, 92:3, 119-130, DOI: 10.1080/00325481.1992.11701444 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701444
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [Monash University Library]
Date: 10 June 2016, At: 16:58
-@CME credit article
Anticoagulant therapy for atrial fibrillation Recommendations from major studies
Joel K. Kahn, MD
Downloaded by [Monash University Library] at 16:58 10 June 2016
Preview When should anticoagulants be used in patients with atrial fibrillation? Which patients should receive aspirin alone? What risk factors exclude patients from such management? Dr Kahn examines the results of four recent studies and discusses the appropriate application of anticoagulant therapy in clinical practice.
Atrial fibrillation affects 2% of the general population and 5% of persons older than 60 years of age. 1 Two aspects of the disorder demand clinical attention: (1) the rapid ventricular rate in patients with new-onset atrial fibrillation and (2) the long-term risk of thromboembolic events. In patients with new-onset atrial fibrillation, a rapid ventricular rate response may lead to breathlessness, chest discomfon, light-headedness, or even syncope. Early treatment therefore focuses on control of the ventricular rate with agents that slow conduction through the atrioventricular node, such as digoxin (Lanoxicaps, Lanoxin), beta blockers, and calcium blockers. Cardioversion also may be required if hemodynamic instability is caused by the rapid ventricular rate. Reducing the long-term risk of thromboembolic events, predominantly cerebrovascular accidents, is a major challenge to physicians caring for patients with atrial fi-
brillation. Indeed, atrial fibrillation is the most common cardiac disorder predisposing to systemic embolism. 1 Until recently, decisions regarding the use of anticoagulants in patients with atrial fibrillation were largely empirical and limited to those with mitral stenosis. Now, however, several recent studies have provided insight into the use of anticoagulants in a broader range of patients. These are reviewed with an emphasis on practical implications for management in clinical practice.
Chronic atrial fibrillation Over the years, rheumatic valvular disease has often been accompanied by chronic atrial fibrillation. From 40% to 80% of patients who require surgery for symptomatic rheumatic valvular disease have chronic atrial fibrillation. Funhermore, in the Framingham Hean Study, it was found that the risk of stroke in patients with rheumatic hean disease and atrial fibrillation was eighteenfold
higher than the risk in controls. 2 A number of largely retrospective studies of the role of chronic anticoagulation in patients with rheumatic atrial fibrillation collectively demonstrated a reduction in the occurrence of systemic emboli, pulmonary emboli, and death in patients who received anticoagulants. 1 It has become common practice to prescribe warfarin sodium (Coumadin, Panwarfin, Sofarin) in patients with rheumatic valvular disease complicated by atrial fibrillation, although the value of long-term anticoagulant therapy has never been confirmed in a well-designed prospective trial. 1 In patients with an absolute contraindication to warfarin therapy, daily aspirin therapy may serve as an alternative. In the Framingham Hean Study, it was noted that the risk of stroke was sixfold higher in patients with nonrheumatic atrial fibrillation than in controls. Until several recent randomized trials were completed, however, the proper role of anticoagulant therapy in patients who have atrial fibrillation associated with such conditions as hypenension, coronary anery disease, and cardiomyopathy was uncenain. Indeed, a consensus panel reviewing the world literature in 1989 concluded that the data were inconclu-
continued
VOL 92/NO 3/SEPTEMBER 1. 1992/POSTGRADUATE MEDICINE • ATRIAL I'IBRILLAnGN
119
Downloaded by [Monash University Library] at 16:58 10 June 2016
Investigators in the AFASAK Study concluded that 75 mg of aspirin daily was ineffective in reducing the incidence of thromboembolic events in patients with atrial fibrillation.
sive regarding the routine use of anticoagulants in patients with nonrheumatic atrial fibrillation. 1 Fortunately, the results of four recent, large randomized trials investigating the role of long-term anticoagulant therapy in nonrheumatic chronic atrial fibrillation have been published and they provide a basis on which to make clinical recommendations. The studies include the Copenhagen Atrial Fibrillation, Aspirin, Anticoagulation (AFASAK) Study, Stroke Prevention in Atrial Fibrillation (SPAF) Study, Boston Area Anticoagulation Trial for Atrial Fibrillation (BMTAF), and Canadian Atrial Fibrillation Anticoagulation (CAFA) Study (see box on page 122).
Study results with warfarin The AFASAK Study was stopped prematurely because of a significant reduction in the incidence of thromboembolic events in patients treated with warfarin. During the study, 4 cerebral infarctions and 1 intracerebral hemorrhage occurred in the warfarin group (2% a year) compared with 21 events in the control group (5% a year). Only 1 Joel K. Kahn, MD Dr Kahn is a consulting cardiologist to the Michigan Heart and Vascular Institute, St Joseph Mercy Hospital, Ann Arbor.
120
withdrew from therapy. of the cerebral infarctions in the The CAFA Study was termiwarfarin group occurred during adequate anticoagulation. Also, nated prematurely. At the point of termination, an intention-toduring the study period, 38% of treat analysis identified 11 pripatients assigned to the warfarin group discontinued therapy. Half mary events in the control group (4.6% a year) compared with of these patients refused to con8 in the warfarin group (3.4% a tinue; side effects and noncomyear). During the study, 26% of pliance were additional common patients on warfarin withdrew reasons for withdrawal. from treatment. In the SPAF Study, randomMajor complications due to ization to the placebo arm was chronic anticoagulation were also terminated prematurely. At the time of termination, 6 strokes tracked in all four of the major had occurred in the warfarin trials (table 1). Because of careful monitoring of warfarin therapy group (2% a year) compared with 18 events (17 strokes, 1 sysand the low doses used, major temic embolism) in the control and fatal bleeding complications group (7% a year). In only 2 of were infrequent. Mi?or bleeding the 6 patients who had a stroke was more common m groups asin the warfarin group was antisigned to warfarin, despite strincogulation adequate at the time gent selection criteria. of the stroke. During the trial, 11% of warfarin patients withStudy results with aspirin drew from therapy. This was In two of the trials, AFASAK and most commonly due to poor SPAF, patients were randomized compliance, secondary events, or to either aspirin or placebo. In exclusion criteria such as angiothe AFASAK Study, 21 primary plasty, bypass surgery, or venous events were identified in placebothrombosis. treated patients and 20 events in BMTAF was completed with aspirin-treated patients, and the 212 patients in the warfarin investigators therefore concluded group and 208 in the control that 75 mg of aspirin daily was group. At completion, there had ineffective in reducing the incibeen 2 strokes in the warfarin dence of thromboembolic events. group (0.4% a year) compared In contrast, during the SPAF with 13 in the placebo group Study, 46 primary events oc(3% a year). During the study, curred in the placebo arm (6% a only 10% of warfarin patients year) compared with 26 events in
ATRIAL FIBRILLATION • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRAOUATE MEDICINE
Downloaded by [Monash University Library] at 16:58 10 June 2016
Systemic embolism is the most serious potential complication of cardioversion in patients with atrial fibrillation.
the aspirin group (4% a year), a significant reduction. A subgroup analysis indicated that all of the benefits from aspirin occurred in patients younger than 75. In patients older than 75, the yearly rate of stroke was identical in the aspirin and placebo groups (7.4% a year), whereas in patients 75 or younger the rate was 6.2% a year in the placebo arm compared with 2.2% a year in the aspirin arm. 3 Patients in BAATAF were not randomized to aspirin therapy, but the number of patients in the placebo group who took aspirin was logged. Of the 13 strokes in the control group, 8 occurred in patients taking aspirin; thus there appeared to be no reduction in the incidence of stroke among control patients taking aspirin.
Acute-onset atrial fibrillation In the four trials reviewed here, the role of long-term anticoagulation in patients with predominantly chronic atrial fibrillation (and, less frequently, recurrent paroxysmal atrial fibrillation) was examined. Not reviewed was the role of immediate intravenous anticoagulation with heparin in patients presenting to the hospital or office with new-onset atrial fibrillation. The most often repeated clinical teaching has been that anticoagulation is unnecessary in patients who have acute
atrial fibrillation of less than 1 week's duration, even if cardiaversion is performed. 4 An alternative premise has been that patients with acute atrial fibrillation ofless than 3 days' duration do not require anticoagulation even if cardioversion is performed. 5 A recent consensus panel indicated that antithrombotic therapy is not necessary for atrial fibrillation of less than 2 days' duration, but the panel also acknowledged the lack of controlled data to guide therapy in such cases.' At present, there are no data to indicate that intravenous anticoagulants need to be initiated for new-onset atrial fibrillation on the day of admission. Prospective studies, however, are needed to determine whether the costs and bleeding risk accompanying routine early intravenous anticoagulation in patients presenting with newonset atrial fibrillation is justified by a reduction in clinical thromboembolic events. Although it is usually possible to estimate the duration of newly diagnosed atrial fibrillation by a carefully taken history that determines the time of onset of dyspnea, chest pain, or palpitations, occasionally the time cannot be definitely ascertained. In such instances, it is probably most appropriate to assume that the
arrhythmia is chronic and to institute anticoagulation with warfarin, if possible.
Elective cardioversion Management of patients with atrial fibrillation often involves attempts at restoring sinus rhythm through pharmacologic or electrical cardioversion. Systemic embolism is the most serious potential complication of cardioversion. There is not a single randomized prospective study of the role of anticoagulant therapy in reducing embolic events due to cardioversion. This issue has been examined in numerous retrospective clinical reports, however, and recommendations have been made regarding the use of anticoagulants in patients scheduled for cardioversion.'·6 It is generally recommended that patients with chronic atrial fibrillation be given warfarin for 3 to 4 weeks before scheduled cardioversion and for 3 to 4 weeks after the attempt if it is successful. No data suggest that pharmacologic cardioversion is any less likely than electrical cardioversion to cause systemic embolism, and several weeks of anticoagulation should probably precede pharmacologic cardioversion attempts, even when agents such as quinidine and procainamide hydrochloride (Pronestyl)
continued
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • ATRIAL FIBRILLAnGN
121
Downloaded by [Monash University Library] at 16:58 10 June 2016
Four major trials have consistently demonstrated a statistically and clinically important reduction in the incidence of strokes and systemic emboli in patients treated with low-dose warfarin therapy.
Study design and patient recruitment for recent studies on anticoagulant therapy for nonrheurnatic atrial fibrillation
Copenhagen Atrial Fibrillation, Aspirin, Anticoagulation (AFASAK) Study This was the first randomized, prospective evaluation of antithrombotic therapy for nonrheumatic atrial fibrillation. 1 It took place between 1985 and 1988 in a single center and had an enrollment of 1,007 patients with chronic atrial fibrillation. There was no upper age limit. Patients with thyroid disease constituted 5% of the group. Patients were randomized to receive either warfarin sodium, 75 mg of aspirin daily, or placebo. Warfarin was given openly, but aspirin and placebo were given in a double-blind manner. The warfarin dosage was adjusted for a prothrombin time {PT) ratio of 1.5 to 2.0 compared with control. The primary end point was a thromboembolic complication (transient ischemic attack, stroke, or embolism to the viscera or extremities). The secondary end point was death. Bleeding complications were classified as minor, major {requiring medical therapy), or fatal. The analysis was based on actual therapy received. Initial plans called for enrollment of 2,000 patients who were to be observed for 2 years, but the trial was terminated when an interim analysis identified a trend favoring the warfarin arm.
patients were excluded from consideration for the trial, most often because of inability to give informed consent, the presence of prosthetic heart valves, life expectancy that was less than 24 months, or transient, self-limited atrial fibrillation. There were 1,330 eligible and consenting patients. A subgroup of 627 patients were considered suitable for anticoagulant therapy with warfarin and were randomly assigned to either warfarin, 325 mg of aspirin daily, or placebo. The 703 eligible patients who were not candidates for anticoagulant therapy were randomized separately to aspirin or placebo. Patients younger than age 50 with lone atrial fibrillation were not randomized to warfarin therapy because the risk of stroke in this subgroup was believed to be too low to justify it. APT ratio of 1.3 to 1.8 was targeted for patients treated with warfarin. Intermittent atrial fibrillation was present in 34% of patients. Patients with thyroid disease and severe heart failure and mitral regurgitation were excluded. Primary end points assessed were ischemic strokes and systemic embolic events. Secondary end points were death, myocardial infarction, transient ischemic attacks, and unstable angina pectoris. The study design called for 1,644 patients to be observed for 3 years, but the study was stopped after the 1,330 patients were enrolled for a mean of 1.3 years of follow-up because a monitoring committee identified advantages in the antithrombotic arms. An intention-to-treat analysis was used.
Stroke Prevention in Atrial Fibrillation (SPAF) Study This trial took place between 1987 and 1989 in 15 centers across the United States. 2 A total of 17,046
Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) This randomized trial assessed the efficacy of lowdose warfarin therapy for nonrheumatic atrial fibril-
The following four major studies, now completed, were designed to investigate the role oflong-term anticoagulant therapy in patients who have nonrheumatic atrial fibrillation.
122
ATRIAL FIBRILLAnON • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE
Downloaded by [Monash University Library] at 16:58 10 June 2016
BAATAF was interrupted prematurely because of strong evidence favoring use of warfarin for anticoagulation therapy in patients with nonrheumatic atrial fibrillation.
!arion. It rook place between 1987 and 1990 in 32 centers in the northeastern United Srares. 3 Patients with chronic and intermittent atrial fibrillation were included; 17% of study patients had intermittent atrial fibrillation. Patients with severe congestive heart failure and hyperthyroidism were excluded. The number of patients screened for enrollment was nor reported. Patients were assigned to receive either warfarin therapy or placebo. Neither the patients nor their physicians were blinded to the assigned therapy. To give the study an 80% power to detect a reduction in the yearly rare of stroke from 5 per 100 patientyears to 1 per 100 patient-years, 400 patients were recruited to be followed for an average of 4.1 years. An intention-to-treat analysis was used. The warfarin group had dosages adjusted to PT ratios of 1.2 to 1. 5, the lowest of the four trials described here. Patients randomly assigned to the placebo group were permitted to take aspirin, and 46% of all patient-years in the placebo group represented participants taking aspirin. The primary end points were ischemic stroke and peripheral systemic thromboembolism. Major bleeding was defined as intracranial bleeding, fatal bleeding, or bleeding requiring transfusion of 4 or more units of blood within 48 hours. The study was interrupted prematurely by the monitoring committee after evidence favoring use of warfarin was judged strong enough to end the trial.
Canadian Atrial Fibrillation Anticoagulation (CAFA) Study This randomized, double-blind, placebo-controlled trial rook place between 1985 and 1989 in 11 Canadian centers.• Recruitment of 630 patients was
originally planned, bur the study was stopped when positive results of rhe AFASAK and SPAF studies were published.1.2 The mean follow-up of the 383 patients enrolled at that point was IS months. Patients with paroxysmal or chronic atrial fibrillation were included. Patients with hyperthyroidism were excluded bur those with severe congestive heart failure were randomized to therapy. During 8 months of the trial, derailed records indicated that only 6% of patients screened for the trial were randomized. Assignment to warfarin therapy to achieve a PT ratio of 1.3 to 1.6 was blinded from the patient and investigators by providing sham PT results for placebo patients. The primary end points were ischemic stroke, other systemic emboli, and intracranial or fatal hemorrhage. Secondary end points were myocardial infarction, death, major bleeding, minor bleeding, or transient ischemic attacks. An efficacy analysis that excluded events occurring more than 28 days after discontinuation of therapy was the primary analysis; an intention-to-treat analysis was secondary. References 1. Petersen P, Boysen G, Godtfred.sen J, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAKstudy. Lancet 1989;1{8631):175-9 2. Stroke Prevention in Atrial Fibrillation Investigators. Stroke Prevention in Atrial Fibrillation Study: final results. Circulation 1991; 84(2):527-39 3. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Eng! J Med 1990; 323(22): 1505-11 4. Connolly SJ, Laupacis A, Gent M, et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. JAm Coil Cardiol1991;18(2): 349-55
VOL 92/NO 3/SEPTEMBER 1. 1992/POSTGRADUATE MEDICINE • ATRIAL FIBRILLAnON
123
Downloaded by [Monash University Library] at 16:58 10 June 2016
Many patients with nonrheumatic atrial fibrillation are not eligible for long-term warfarin therapy.
Table 1. Hemorrhagic complications of long-term anticoagulation therapy with warfarin for nonrheumatic atrial fibrillation in four major studies Intracerebral hemorrhage Warfarin Control
AFASAK
0
SPAF
0
BMTAF
0
CAFA
0
Major bleeding
Warfarin
3
4
Minor bleeding
Control
Warfarin
0
21
4
4
2
Control 0
38
21
37
28
AFASAK, Copenhagen Atrial Fibrillation, Aspirin, Anticoagulation Study; BAATAF, Boston Area Anticoagulation Trial for Atrial Fibrillation; CAFA, Canadian Atrial Fibrillation Anticoagulation Study; SPAF, Stroke Prevention in Atrial Fibrillation Study.
Table 2. High- and low-risk factors for thromboembolic complications in patients with atrial fibrillation High-risk factors Rheumatic valve disease Advanced age Severe congestive heart failure Ventricular aneurysm Previous emboli Previous myocardial infarction lntracardiac thrombus Low-risk factors Lone atrial fibrillation Paroxysmal atrial fibrillation
124
are used. An exception would be in patients with new-onset atrial fibrillation ofless than 2 to 7 days' duration, as has been discussed.
Discussion The four randomized trials of anticoagulant therapy in patients with nonrheumatic atrial fibrillation collectively clarify recommendations for management of these patients in clinical practice. Even after excluding many groups of patients believed to be at high risk for thromboembolic complications of atrial fibrillation (table 2), the yearly risk of stroke or systemic embolism in patients with nonrheumatic atrial fibrillation
was 5% to 7% a year in the trials. Many of these events were disabling or fatal. The trials were consistent in demonstrating a statistically and clinically imponant reduction in the incidence of strokes and systemic emboli in patients who were treated long-term with low-dose warfarin therapy; this reduction was accomplished in exchange for a small bleeding risk. It has been estimated from the SPAF Study that for 1,000 patients similar to those enrolled in the warfarin study arm, 51 fewer strokes or systemic emboli (26 of which might have been severely disabling or fatal) could be anticipated as a result of longterm anticoagulant therapy in exchange for 4 bleeding events with residua. 7 The risk-benefit ratio is clearly in favor of low-dose warfarin therapy. Therefore, in addition to patients with rheumatic atrial fibrillation and those with prosthetic hean valves associated with atrial fibrillation, patients with nonrheumatic atrial fibrillation should be routinely treated with long-term warfarin therapy if there are no contraindications (table 3). Several additional lessons of clinical imponance can be derived from these recent trials. One is that many patients with nonrheumatic atrial fibrillation continued on page 129
ATRIAL FIBRILLATION • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE
Downloaded by [Monash University Library] at 16:58 10 June 2016
Continued encouragement and reinforcement regarding the importance of anticoagulation therapy are necessary to maintain patient commitment.
are not eligible for long-term warfarin therapy. Over 90% of patients screened for two of the trials were excluded. While many of these exclusions were for administrative reasons or because of a preexisting requirement for antithrombotic therapy, patients believed to be at high risk for bleeding from warfarin therapy were carefully excluded from all of the trials. Reproducing the overall favorable results of the trials in general clinical practice will therefore require similar careful selection of patients. A second lesson from the trials arises from the fact that many patients thought to be at highest risk for thromboembolic complications were excluded from the studies because withholding warfarin was considered inappropriate. Therefore, even though the advantages of warfarin therapy were not examined in patients who had atrial fibrillation with severe congestive heart failure, severe mitral regurgitation, recent embolic episodes, recent myocardial infarction, dilated cardiomyopathies, or prosthetic heart valves, such patients should be given anticoagulant therapy unless a major contraindication exists. Another observation from the studies relevant to clinical practice is that one tenth to one third
of patients withdrew from therapy, most commonly because of the inconvenience of frequent trips for prothrombin time measurements. Continued encouragement and reinforcement regarding the imponance of therapy are necessary to maintain patient commitment. Several questions remain unresolved by these trials. One is the proper role of aspirin in reducing the incidence of thromboembolic events. The conclusions of the AFASAK and SPAF studies were in opposition regarding the efficacy of aspirin, although statistically the findings in these two trials do overlap. 8 One obvious conclusion is that 75 mg of aspirin daily may be inadequate to prevent embolic events; a higher daily dosage of 325 mg (as used in the SPAF Study) should therefore be prescribed in clinical practice. A second conclusion is that aspirin may be less effective in patients over 75 years old, as was observed in the SPAF Study. The mean age of patients in the AFASAK Study (74) was higher than that in the SPAF Study (67), and this may have resulted in less impressive results. There is no direct comparison of aspirin and warfarin therapy available at this writing, although several trials, including a SPAF II study, are in progress and are
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • ATRIAL FIBRILLATION
Table 3. Risk factors for excessive bleeding with longterm anticoagulant therapy
Known bleeding disorder Previous hemorrhage with anticoagulant therapy Active peptic ulcer disease Alcoholism Uncontrolled hypertension Gait disorders or frequent syncope Severe renal or hepatic diseases Recent stroke
comparing the efficacy of these two agents. For now, it would appear that patients with nonrheumatic atrial fibrillation who are ineligible for warfarin therapy should be treated with 325 mg of aspirin daily, if at all possible. Whether this approach also benefits the very elderly needs to be clarified in ongoing studies. Two other patient groups deserve mention. First, patients younger than 50 to 60 years old who have atrial fibrillation and no evidence of structural heart disease (lone atrial fibrillation) are at very low risk for thromboembolic events.9 These patients continued
129
Downloaded by [Monash University Library] at 16:58 10 June 2016
Young patients who have paroxysmal atrial fibrillation without structural heart disease probably should be treated with aspirin alone.
Summary were excluded from the SPAF Study and were infrequent particThe role of antithrombotic ipants in the other studies. Until further information is available, therapy in reducing thromboembolic complications in pathey probably should be treated tients with chronic atrial fibrilwith daily aspirin therapy only. lation has been clarified by the The second group of patients includes those with paroxysmal results of four major randomatrial fibrillation. These patients ized and placebo-controlled were excluded from the AFASAK trials. Patients with rheumatic Study but accounted for about heart disease complicated by 10% to 30% of patients in the atrial fibrillation should receive other three trials. Although the long-term warfarin therapy to trials do not provide any definite reduce the risk of stroke unless guidelines, these patients have an absolute contraindication been found to have a consistently exists. Patients with nonrheulower risk of stroke in studies that matic atrial fibrillation should have compared paroxysmal with also be treated with low-dose chronic atrial fibrillation. 8 Young warfarin therapy, especially if patients who have paroxysmal high-risk features for thromboatrial fibrillation without strucembolism exist. In patients who tural heart disease probably should be treated with aspirin alone, whereas older patients or those with structural heart disease References should be treated with low-dose 1. Dunn M, Alexander J, de Silva R, et al. warfarin, if at all possible. Antithrombotic therapy in atrial fibrillation. Chest 1989;95(2 Suppl):118-27S Because of the short period of 2. Kannel WB, Abbott RD, Savage DD, et observation in the randomized al. Epidemiologic features of chronic atrial fitrials, additional follow-up of the brillation: the Framingham study. N Eng! J Med 1982;306(17):1018-22 participants is necessary to assess 3. Stroke Prevention in Atrial Fibrillation Inthe optimal duration of therapy vestigators. Preliminary report of the Stroke with antithrombotic agents. It Prevention in Atrial Fibrillation Study. N Eng! J Med 1990;322(12):863-8 would seem prudent to continue 4. DeSilva RA, Graboys TB, Podrid PJ, et al. antithrombotic therapy indefiCardioversion and defibrillation. Am Heart J nitely in patients with chronic 1980;100(6 Pt 1):881-95 5. Bjerkelund CJ, Orning OM. The efficacy of atrial fibrillation unless a new anticoagulant therapy in preventing embolism contraindication or a bleeding related to D.C. electrical conversion of atrial ficomplication occurs. brillation. Am J Cartliol 1969;23(2):208-16
130
have contraindications to warfarin therapy and in young patients with lone atrial fibrillation or paroxysmal atrial fibrillation, therapy with 325 mg of aspirin a day is preferred. Ongoing trials directly comparing aspirin and warfarin will provide additional insight into the optimal role of these antithrombotic agents in patients with atrial fibrillation. Rl't'l
-®
Earn credit on this article. See CME Qui,,
Address for correspondence: Joel K Kahn, MD, 5333 McAuley Dr, Suite 3009, Ann Arbor, MI 48106.
6. Stein B, Halperin JL, Fuster V. Should patients with atrial fibrillation be anticoagulated prior to and chronically following cartlioversion? In: Cheiclin MD, ed. Dilemmas in clinical cardiology. Vol21. Philadelphia: FA Davis, 1990: 231-49 7. Cairns JA. Stroke prevention in atrial fibrillation trial. (Etlitorial) Circulation 1991;84(2): 933-5 8. Cairns JA, Connolly SJ. Nonrheumatic atrial fibrillation: risk of stroke and role of antithrombotic therapy. Circulation 1991; 84(2):469-81 9. Kopecky SL, Gersh BJ, McGoon MD, et al. The natural history oflone atrial fibrillation: a population-based study over three decades. N Eng! J Med 1987;317(11):669-74
ATRIAL FIBRILLATION • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE
