Anticoagulant Decisions in Intermittent Atrial Fibrillation
Anticoagulant Decisions in Intermittent Atrial Fibrillation
Abstract & Commentary
By John P. DiMarco, MD, PhD
Source: Glotzer TV, et al. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk. The TRENDS Study. Circ Arrhythmia Electrophysiol. 2009;2:474-480.
Modern implantable cardioverter defibrillators (ICDs) and permanent pacemakers can store all data about atrial tachyarrhythmias. In this study, the TRENDS investigators sought to examine the relationship between the risk for thromboembolic events and recorded atrial-tachycardia and atrial-fibrillation (AT/AF) episodes in patients receiving implantable devices. Patients were eligible for inclusion if they had an established indication for implantation of a pacemaker or ICD that was capable of long-term monitoring of AT/AF burden and also had one or more risk factors for stroke or embolic events based on the 2001 guidelines. These risk factors included: a history of congestive heart failure or hypertension, age less than or equal to 65 years, diabetes mellitus, and prior stroke or transient ischemic attack (TIA). Patients with longstanding, persistent AF were excluded. After implantation, patients were followed at three-month intervals, at which time device diagnostic information was collected. Anti-thrombotic therapy was prescribed at the discretion of the patients' physicians. All devices were programmed to dual-chamber operation with active-mode switching. AT/AF detection was set at 175 bpm for greater than 20 seconds in all devices. Stored intracardiac electrograms could not be analyzed for every episode because of device memory limitations, so atrial rate was the primary criterion used. AT/AF burden was measured in hours per day and was tabulated daily by the device. The primary study outcome events were ischemic stroke, TIA, and systemic embolism. Outcome events were adjudicated by a committee of three neurologists.
Initially, the study plan sought to determine the relationship between median daily AT/AF burden and thromboembolic events in patients not treated with warfarin in the first year after device implantation. After patients receiving warfarin and those with no episodes of AT/AF were excluded, there remained 818 patients in the primary study group. Among these patients, there were only 14 thromboembolic events. The event rate was, therefore, too low for statistically meaningful analysis. In this paper, a secondary analysis of the overall study group is reported in this secondary analysis. Patients who were anticoagulated and those who do not have AT/AF were included. After exclusion of patients who did not have at least 30 days of device data available for analysis, a study group of 2,486 patients was available. For the overall study group, the mean age was 70.9 ± 11 years. Pacemakers were implanted in approximately 50% of the patients, ICDs in 31%, and cardiac-resynchronization therapy devices in 19%. The mean CHADS2 score was 2.2 ± 1.2. Sixty-three percent of the patients had a history of coronary artery disease and 20% had a previously documented episode of atrial fibrillation. At baseline, 20.8% were receiving warfarin, 62% were receiving aspirin, 9.9% were on an antiarrhythmic drug, and 22.5% were on other antiplatelet therapy.
AT/AF burden was defined as the maximum daily duration of AT/AF episodes on any given day during the preceding 30-day window. The observed median value for AT/AF burden was 5.5 hours in those patients with any AT/AF. Fifty-three percent of the study patients had no AT/AF observed any time during follow-up and 76% of the 30-day windows had 0 AT/AF burden. During an average follow-up of 1.4 years, there were 40 patients who had thromboembolic events with device data available for the 30-day window immediately preceding the event. In this group, there were 20 ischemic strokes, 17 TIAs, and three systemic emboli for an annualized event rate of 1.2%. Thromboembolic event rates were analyzed in three groups. One group had zero AT/AF burden. The second group had an AT/AF burden in the 30-day window lower than the median value of 5.5 hours and the third group had high AT/AF burden (greater than 5.5 hours on any day). The annualized thromboembolic event was 1.1% for both the groups, with 0 AT/AF burden and with low AT/AF burden, respectively. For the group with high AT/AF burden, the annualized thromboembolic event was 2.4%.
To clarify the data, a Cox regression analysis was performed to adjust for stroke risk factors at baseline. This resulted in a hazard ratio of 0.98% for the low AT/AF burden subset compared to the zero AT/AF burden subset. The hazard ratio for the high AT/AF burden subset compared with the zero AT/AF burden subset was 2.2. In an alternate analysis, the AT/AF burden was analyzed as the total cumulative hours of AT/AF over the prior 30 days. The median value for this measure for those who had any AT/AF was 10.8 hours. Similar hazard ratios to the analysis using the 5.5 hour daily measurement in the 30-day window were seen with hazard ratios of 0.97 between the low AT/AF subset and the zero AT/AF subset and a hazard ratio of 2.22 between the high AT/AF subset and the 0 AT/AF subset.
The authors emphasize two major findings in the TRENDS study. They note a remarkably low thromboembolic event rate in a large group of patients with moderately high mean CHADS2 scores and implanted devices. The rate of thromboembolic events was low even among those with episodes of AT/AF. However, thromboembolic risk does appear to be quantitatively linked to AT/AF burden, with the cut-off values found to be less than 5.5 hours per day or less than 10.8 hours per 30-day period. If these findings can be applied to all patients with intermittent atrial fibrillation, more selective use of anticoagulation may be possible.
Commentary
Current guidelines suggest that patients with both persistent and paroxysmal atrial fibrillation and risk factors for stroke should receive appropriate anticoagulation. This guideline conclusion is made based upon observations from randomized clinical trials of anticoagulation with warfarin vs. placebo. These trails have reported that the risk for embolic events was similar for patients classified as having intermittent vs. continuous AF in the trials. However, in those early trials, intermittent or paroxysmal atrial fibrillation was usually defined as being present in any patient who had a single ECG showing sinus rhythm throughout the course of the trial. It is likely that many of these patients had long episodes of atrial fibrillation, not the short, asymptomatic episodes that are frequently observed in the general population. How to manage patients with short runs of AT/AF, particularly when they are asymptomatic, remains an important unanswered question. The TRENDS data reported in this patient suggest that every episode of AF should not trigger anticoagulation therapy.
The TRENDS data are supported by other studies showing that some duration of atrial fibrillation is required to increase stroke risk. For example, in another study of patients with pacemakers (J Am Coll Cardiol. 2005;46:1913-1920), Capucci et al found that embolic risk increased only in those patients with episodes of more than 24 hours duration.
Data from patients with pacemakers and ICDs may not be representative of the general population, but studies such as this are the only practical way to look at the importance of asymptomatic AT/AF. If the data here can be confirmed in other trials, we may be able to revise the guidelines and decrease the number of patients for whom anticoagulation, with all its inherent problems, is recommended.
Correction
In the "Dietary Manipulation to Stabilize INR" article from the November 2009 issue, we stated that... "in the trial, they adjusted INR, if it was high, by cutting the intake of the vitamin K-rich foods by half. If the INR was low, they increased their intake by 100%." It should have read..."in the trial, they adjusted INR, if it was high, by cutting the intake of the vitamin K-rich foods by half. If the INR was low, they increased their intake by 100%." We apologize for any inconvenience.
Modern implantable cardioverter defibrillators (ICDs) and permanent pacemakers can store all data about atrial tachyarrhythmias.Subscribe Now for Access
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