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Study Overview
Objective. To compare radiofrequency ablation (RFA) with antiarrhythmic drugs in treating patients with paroxysmal atrial fibrillation as a first-line therapy.
Design. Randomized controlled trial.
Setting and participants. This multi-center study was conducted at 16 sites in 5 countries and enrolled 127 patients between July 2006 and January 2010. Adult patients < 75 years old with a history of paroxysmal atrial fibrillation who had at least 1 episode of symptomatic paroxysmal atrial fibrillation in the 6 months prior to enrollment and had no previous antiarrhythmic drug treatment were recruited. Patients were excluded if they had structural heart disease or had a complete contraindication for the use of heparin, warfarin, or both.
Patients were randomized by variable block generated by computer to receive either antiarrhythmic drugs or RFA. All patients were followed up at 1, 3, 6, 12, and 24 months after randomization. Each patient received a transtelephonic monitor system and was trained to record and transmit symptomatic episodes of possible atrial fibrillation. Patients were also instructed to transmit biweekly recordings on a Friday, regardless of whether they had experienced symptoms. Blinded experienced electrophysiologists analyzed all recordings, which may also have included scheduled or unscheduled electrocardiogram, Holter, or rhythm strips.
Patients randomized to the antiarrhythmic drug group were administered medications chosen by the investigators. Drug dosages titrated during the 90-day blanking period were maintained throughout the study. Patients in the antiarrhythmic drug group were also allowed to cross over and undergo ablation after 90 days if medical treatment had failed.
Patients randomized to the RFA group underwent circumferential isolation of the pulmonary veins. Additional ablation lesions were also allowed at investigator’s choice. Furthermore, selections of the ablation catheter, power and irrigation settings, as well as the use of navigation systems were left to the discretion of the investigator. Following RFA, anticoagulation with warfarin was maintained for at least 3 months.
Main outcome measures. The primary outcome was time to first recurrence of symptomatic or asymptomatic atrial fibrillation, atrial flutter, or atrial tachycardia lasting more than 30 seconds. Secondary outcomes were symptomatic recurrences of atrial fibrillation, atrial flutter, or atrial tachycardia during the study period and quality of life as measured by EQ-5D Tariff score. There was a 90-day blanking period (the time after randomization when an AF event is not counted).
Main results. The RFA group experienced a significantly lower rate of recurrence of atrial tachyarrhythmias at 2 years compared with the antiarrhythmic drug group (54.5% vs. 72.1%, hazard ratio [HR] 0.56 [95% CI, 0.35–0.90]; P = 0.02). The difference was present but smaller for the rate of symptomatic arrhythmias (47% RFA group vs. 59% drug therapy group, HR 0.56 [95% CI, 0.33–0.95]; P = 0.03). There were no differences among treatment groups in regard to quality of life at 1-year follow-up using the EQ-5D Tariff score. No deaths or strokes reported in either group; 4 cases (6%) of cardiac tampoade were reported in the RFA group.
Conclusion. The authors of this study conclude that for paroxysmal atrial fibrillation patients without previous antiarrhythmic drug treatment, RFA resulted in a lower rate of recurrence of atrial tachyarrhythmias at 2 years compared with standard antiarrhythmic drug treatment. However, recurrence was frequent in both groups after 2 years.
Commentary
Atrial fibrillation is a common arrhythmia associated with an increased risk of stroke and other adverse events. Current practice guidelines recommend antiarrhythmic drugs as the first-line therapy for patients with symptomatic paroxysmal atrial fibrillation. However, a significant proportion of patients are nonadherent with antiarrhythmic therapy. As a result, antiarrhythmic therapy is only 46% effective at 12 months in preventing the recurrence of atrial fibrillation [1].
The purpose of the current study (Radiofrequency Ablation vs. Antiarrhythmic Drugs for Atrial Fibrillation Treatment-2, or RAAFT-2) was to determine whether RFA is superior to antiarrhythmic drugs as first-line therapy in patients with paroxysmal atrial fibrillation who had not been exposed to antiarrhythmic treatment. Over the past decade, various single-center trials attempted to demonstrate the superiority of RAF. Evidence from these trials suggested that RFA resulted in lower burden of atrial fibrillation and more patients free from atrial fibrillation. However, RFA had a higher initial cost, higher rate of complications, and conferred no improvement in the quality of life [2–5].
Despite the statistically significant lower rate of recurrence of atrial tachyarrhythmias in the RFA group, there are many limitations with this multi-center, multi-country study. First, selection bias may have been present, as it took 42 months to recruit 127 patients in 16 centers and 5 countries for a very common disease. Second, the use of a transtelephonic monitor was unique. When the investigators excluded transtelephonic monitor results and used electrocardiogram and Holter monitor results, similar to previous trials, the primary outcomes were no longer different. Third, biases in the study design favor RFA. For example, investigators permitted substantial variation in the RFA procedures but restricted dosage changes in the antiarrhythmic drugs group. Finally, 26 of the 61 patients (42.6%) assigned to the antiarrhythmic drug group crossed over to undergo RFA, and the intention-to-treat basis became invalid.
One might ask, what is the worth of this trial? This trial provides additional evidence about about the risks of RFA. While no deaths or strokes were reported in this trial, 6 of the 66 patients (9.1%) in the RFA group had a serious adverse event, with 4 patients (6%) experiencing pericardial effusion with tamponade. The 6% tamponade rate is similar to that found in previous trials [2]. On the other hand, only 3 of the 61 patients (4.9%) in the antiarrhythmic drugs group experienced a serious adverse event (1 had atrial flutter with 1:1 atrioventricular conduction, 2 had syncope).
Applications for Clinical Practice
This trial of radiofrequency ablation vs. antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation provides further evidence of the risks and benefits of each of these options. The current guidelines should be followed. However, given the high level of medical therapy noncompliance, selected patients should also be given the option of using RFA as primary treatment. Patients who are offered the procedure should be made aware of the risks, and providers should incorporate patient’s risk perceptions and preferences in treatment planning.
—Ka Ming Gordon Ngai, MD, MPH
1. Camm AJ, Lip GY, De Caterina R, et al. 2012 Focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012;33:2719–47.
2. Cosedis Nielsen J, Johannessen A, Raatikainen P, et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med 2012;367:1587–95.
3. Dorian P, Paquette M, Newman D, et al. Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. Am Heart J 2002;143:984–90.
4. Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293;2634–40.
5. Khaykin Y, Wang X, Natale A, et al. Cost comparison of ablation versus antiarrhythmic drugs as first-line therapy for atrial fibrillation: an economic evaluation of the RAAFT pilot study. J Cardiovasc Electrophysiol 2009;20:7–12.
Study Overview
Objective. To compare radiofrequency ablation (RFA) with antiarrhythmic drugs in treating patients with paroxysmal atrial fibrillation as a first-line therapy.
Design. Randomized controlled trial.
Setting and participants. This multi-center study was conducted at 16 sites in 5 countries and enrolled 127 patients between July 2006 and January 2010. Adult patients < 75 years old with a history of paroxysmal atrial fibrillation who had at least 1 episode of symptomatic paroxysmal atrial fibrillation in the 6 months prior to enrollment and had no previous antiarrhythmic drug treatment were recruited. Patients were excluded if they had structural heart disease or had a complete contraindication for the use of heparin, warfarin, or both.
Patients were randomized by variable block generated by computer to receive either antiarrhythmic drugs or RFA. All patients were followed up at 1, 3, 6, 12, and 24 months after randomization. Each patient received a transtelephonic monitor system and was trained to record and transmit symptomatic episodes of possible atrial fibrillation. Patients were also instructed to transmit biweekly recordings on a Friday, regardless of whether they had experienced symptoms. Blinded experienced electrophysiologists analyzed all recordings, which may also have included scheduled or unscheduled electrocardiogram, Holter, or rhythm strips.
Patients randomized to the antiarrhythmic drug group were administered medications chosen by the investigators. Drug dosages titrated during the 90-day blanking period were maintained throughout the study. Patients in the antiarrhythmic drug group were also allowed to cross over and undergo ablation after 90 days if medical treatment had failed.
Patients randomized to the RFA group underwent circumferential isolation of the pulmonary veins. Additional ablation lesions were also allowed at investigator’s choice. Furthermore, selections of the ablation catheter, power and irrigation settings, as well as the use of navigation systems were left to the discretion of the investigator. Following RFA, anticoagulation with warfarin was maintained for at least 3 months.
Main outcome measures. The primary outcome was time to first recurrence of symptomatic or asymptomatic atrial fibrillation, atrial flutter, or atrial tachycardia lasting more than 30 seconds. Secondary outcomes were symptomatic recurrences of atrial fibrillation, atrial flutter, or atrial tachycardia during the study period and quality of life as measured by EQ-5D Tariff score. There was a 90-day blanking period (the time after randomization when an AF event is not counted).
Main results. The RFA group experienced a significantly lower rate of recurrence of atrial tachyarrhythmias at 2 years compared with the antiarrhythmic drug group (54.5% vs. 72.1%, hazard ratio [HR] 0.56 [95% CI, 0.35–0.90]; P = 0.02). The difference was present but smaller for the rate of symptomatic arrhythmias (47% RFA group vs. 59% drug therapy group, HR 0.56 [95% CI, 0.33–0.95]; P = 0.03). There were no differences among treatment groups in regard to quality of life at 1-year follow-up using the EQ-5D Tariff score. No deaths or strokes reported in either group; 4 cases (6%) of cardiac tampoade were reported in the RFA group.
Conclusion. The authors of this study conclude that for paroxysmal atrial fibrillation patients without previous antiarrhythmic drug treatment, RFA resulted in a lower rate of recurrence of atrial tachyarrhythmias at 2 years compared with standard antiarrhythmic drug treatment. However, recurrence was frequent in both groups after 2 years.
Commentary
Atrial fibrillation is a common arrhythmia associated with an increased risk of stroke and other adverse events. Current practice guidelines recommend antiarrhythmic drugs as the first-line therapy for patients with symptomatic paroxysmal atrial fibrillation. However, a significant proportion of patients are nonadherent with antiarrhythmic therapy. As a result, antiarrhythmic therapy is only 46% effective at 12 months in preventing the recurrence of atrial fibrillation [1].
The purpose of the current study (Radiofrequency Ablation vs. Antiarrhythmic Drugs for Atrial Fibrillation Treatment-2, or RAAFT-2) was to determine whether RFA is superior to antiarrhythmic drugs as first-line therapy in patients with paroxysmal atrial fibrillation who had not been exposed to antiarrhythmic treatment. Over the past decade, various single-center trials attempted to demonstrate the superiority of RAF. Evidence from these trials suggested that RFA resulted in lower burden of atrial fibrillation and more patients free from atrial fibrillation. However, RFA had a higher initial cost, higher rate of complications, and conferred no improvement in the quality of life [2–5].
Despite the statistically significant lower rate of recurrence of atrial tachyarrhythmias in the RFA group, there are many limitations with this multi-center, multi-country study. First, selection bias may have been present, as it took 42 months to recruit 127 patients in 16 centers and 5 countries for a very common disease. Second, the use of a transtelephonic monitor was unique. When the investigators excluded transtelephonic monitor results and used electrocardiogram and Holter monitor results, similar to previous trials, the primary outcomes were no longer different. Third, biases in the study design favor RFA. For example, investigators permitted substantial variation in the RFA procedures but restricted dosage changes in the antiarrhythmic drugs group. Finally, 26 of the 61 patients (42.6%) assigned to the antiarrhythmic drug group crossed over to undergo RFA, and the intention-to-treat basis became invalid.
One might ask, what is the worth of this trial? This trial provides additional evidence about about the risks of RFA. While no deaths or strokes were reported in this trial, 6 of the 66 patients (9.1%) in the RFA group had a serious adverse event, with 4 patients (6%) experiencing pericardial effusion with tamponade. The 6% tamponade rate is similar to that found in previous trials [2]. On the other hand, only 3 of the 61 patients (4.9%) in the antiarrhythmic drugs group experienced a serious adverse event (1 had atrial flutter with 1:1 atrioventricular conduction, 2 had syncope).
Applications for Clinical Practice
This trial of radiofrequency ablation vs. antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation provides further evidence of the risks and benefits of each of these options. The current guidelines should be followed. However, given the high level of medical therapy noncompliance, selected patients should also be given the option of using RFA as primary treatment. Patients who are offered the procedure should be made aware of the risks, and providers should incorporate patient’s risk perceptions and preferences in treatment planning.
—Ka Ming Gordon Ngai, MD, MPH
Study Overview
Objective. To compare radiofrequency ablation (RFA) with antiarrhythmic drugs in treating patients with paroxysmal atrial fibrillation as a first-line therapy.
Design. Randomized controlled trial.
Setting and participants. This multi-center study was conducted at 16 sites in 5 countries and enrolled 127 patients between July 2006 and January 2010. Adult patients < 75 years old with a history of paroxysmal atrial fibrillation who had at least 1 episode of symptomatic paroxysmal atrial fibrillation in the 6 months prior to enrollment and had no previous antiarrhythmic drug treatment were recruited. Patients were excluded if they had structural heart disease or had a complete contraindication for the use of heparin, warfarin, or both.
Patients were randomized by variable block generated by computer to receive either antiarrhythmic drugs or RFA. All patients were followed up at 1, 3, 6, 12, and 24 months after randomization. Each patient received a transtelephonic monitor system and was trained to record and transmit symptomatic episodes of possible atrial fibrillation. Patients were also instructed to transmit biweekly recordings on a Friday, regardless of whether they had experienced symptoms. Blinded experienced electrophysiologists analyzed all recordings, which may also have included scheduled or unscheduled electrocardiogram, Holter, or rhythm strips.
Patients randomized to the antiarrhythmic drug group were administered medications chosen by the investigators. Drug dosages titrated during the 90-day blanking period were maintained throughout the study. Patients in the antiarrhythmic drug group were also allowed to cross over and undergo ablation after 90 days if medical treatment had failed.
Patients randomized to the RFA group underwent circumferential isolation of the pulmonary veins. Additional ablation lesions were also allowed at investigator’s choice. Furthermore, selections of the ablation catheter, power and irrigation settings, as well as the use of navigation systems were left to the discretion of the investigator. Following RFA, anticoagulation with warfarin was maintained for at least 3 months.
Main outcome measures. The primary outcome was time to first recurrence of symptomatic or asymptomatic atrial fibrillation, atrial flutter, or atrial tachycardia lasting more than 30 seconds. Secondary outcomes were symptomatic recurrences of atrial fibrillation, atrial flutter, or atrial tachycardia during the study period and quality of life as measured by EQ-5D Tariff score. There was a 90-day blanking period (the time after randomization when an AF event is not counted).
Main results. The RFA group experienced a significantly lower rate of recurrence of atrial tachyarrhythmias at 2 years compared with the antiarrhythmic drug group (54.5% vs. 72.1%, hazard ratio [HR] 0.56 [95% CI, 0.35–0.90]; P = 0.02). The difference was present but smaller for the rate of symptomatic arrhythmias (47% RFA group vs. 59% drug therapy group, HR 0.56 [95% CI, 0.33–0.95]; P = 0.03). There were no differences among treatment groups in regard to quality of life at 1-year follow-up using the EQ-5D Tariff score. No deaths or strokes reported in either group; 4 cases (6%) of cardiac tampoade were reported in the RFA group.
Conclusion. The authors of this study conclude that for paroxysmal atrial fibrillation patients without previous antiarrhythmic drug treatment, RFA resulted in a lower rate of recurrence of atrial tachyarrhythmias at 2 years compared with standard antiarrhythmic drug treatment. However, recurrence was frequent in both groups after 2 years.
Commentary
Atrial fibrillation is a common arrhythmia associated with an increased risk of stroke and other adverse events. Current practice guidelines recommend antiarrhythmic drugs as the first-line therapy for patients with symptomatic paroxysmal atrial fibrillation. However, a significant proportion of patients are nonadherent with antiarrhythmic therapy. As a result, antiarrhythmic therapy is only 46% effective at 12 months in preventing the recurrence of atrial fibrillation [1].
The purpose of the current study (Radiofrequency Ablation vs. Antiarrhythmic Drugs for Atrial Fibrillation Treatment-2, or RAAFT-2) was to determine whether RFA is superior to antiarrhythmic drugs as first-line therapy in patients with paroxysmal atrial fibrillation who had not been exposed to antiarrhythmic treatment. Over the past decade, various single-center trials attempted to demonstrate the superiority of RAF. Evidence from these trials suggested that RFA resulted in lower burden of atrial fibrillation and more patients free from atrial fibrillation. However, RFA had a higher initial cost, higher rate of complications, and conferred no improvement in the quality of life [2–5].
Despite the statistically significant lower rate of recurrence of atrial tachyarrhythmias in the RFA group, there are many limitations with this multi-center, multi-country study. First, selection bias may have been present, as it took 42 months to recruit 127 patients in 16 centers and 5 countries for a very common disease. Second, the use of a transtelephonic monitor was unique. When the investigators excluded transtelephonic monitor results and used electrocardiogram and Holter monitor results, similar to previous trials, the primary outcomes were no longer different. Third, biases in the study design favor RFA. For example, investigators permitted substantial variation in the RFA procedures but restricted dosage changes in the antiarrhythmic drugs group. Finally, 26 of the 61 patients (42.6%) assigned to the antiarrhythmic drug group crossed over to undergo RFA, and the intention-to-treat basis became invalid.
One might ask, what is the worth of this trial? This trial provides additional evidence about about the risks of RFA. While no deaths or strokes were reported in this trial, 6 of the 66 patients (9.1%) in the RFA group had a serious adverse event, with 4 patients (6%) experiencing pericardial effusion with tamponade. The 6% tamponade rate is similar to that found in previous trials [2]. On the other hand, only 3 of the 61 patients (4.9%) in the antiarrhythmic drugs group experienced a serious adverse event (1 had atrial flutter with 1:1 atrioventricular conduction, 2 had syncope).
Applications for Clinical Practice
This trial of radiofrequency ablation vs. antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation provides further evidence of the risks and benefits of each of these options. The current guidelines should be followed. However, given the high level of medical therapy noncompliance, selected patients should also be given the option of using RFA as primary treatment. Patients who are offered the procedure should be made aware of the risks, and providers should incorporate patient’s risk perceptions and preferences in treatment planning.
—Ka Ming Gordon Ngai, MD, MPH
1. Camm AJ, Lip GY, De Caterina R, et al. 2012 Focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012;33:2719–47.
2. Cosedis Nielsen J, Johannessen A, Raatikainen P, et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med 2012;367:1587–95.
3. Dorian P, Paquette M, Newman D, et al. Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. Am Heart J 2002;143:984–90.
4. Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293;2634–40.
5. Khaykin Y, Wang X, Natale A, et al. Cost comparison of ablation versus antiarrhythmic drugs as first-line therapy for atrial fibrillation: an economic evaluation of the RAAFT pilot study. J Cardiovasc Electrophysiol 2009;20:7–12.
1. Camm AJ, Lip GY, De Caterina R, et al. 2012 Focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012;33:2719–47.
2. Cosedis Nielsen J, Johannessen A, Raatikainen P, et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med 2012;367:1587–95.
3. Dorian P, Paquette M, Newman D, et al. Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. Am Heart J 2002;143:984–90.
4. Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293;2634–40.
5. Khaykin Y, Wang X, Natale A, et al. Cost comparison of ablation versus antiarrhythmic drugs as first-line therapy for atrial fibrillation: an economic evaluation of the RAAFT pilot study. J Cardiovasc Electrophysiol 2009;20:7–12.