EARLY-AF: Cryoballoon ablation bests antiarrhythmic drugs as first-line intervention
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Cryoballoon ablation was associated with significant improvement over antiarrhythmic drugs as a first-line intervention in preventing atrial fibrillation events, according to the results of the EARLY-AF trial.
“Currently, contemporary guidelines recommend a trial of antiarrhythmic drugs prior to considering catheter ablation,” Jason G. Andrade, MD, director of the Atrial Fibrillation Clinic, Electrodiagnostics and Cardiac Electrophysiology at the Vancouver Coastal Health Research Institute, said during his presentation at the virtual American Heart Association Scientific Sessions. “However, we recognize that antiarrhythmic drugs have limited benefit as well as potential toxicities. Ablation is more effective when performed early.”
The time to a first recurrence of a symptomatic or asymptomatic atrial tachyarrhythmia — defined as AF, atrial flutter or atrial tachycardia — lasting 30 or more seconds between days 91 and 360 after treatment initiation was the primary endpoint. The outcome was assessed by an implantable continuous rhythm monitor (CareLink, Medtronic).
Secondary endpoints included time to first recurrence of a symptomatic atrial tachyarrhythmia over the same duration and total arrhythmia burden as assessed by the proportion of time in AF as detected by continuous monitoring. Also assessed were quality of life parameters, ED visit or hospitalization, repeat ablation procedures and adverse events.
The analysis included 303 patients with treatment-naive, symptomatic AF who were randomly assigned first-line ablation or an antiarrhythmic drug. The findings were simultaneously published in The New England Journal of Medicine.
At approximately aged 58 years, Andrade described the study population as “relatively young and healthy.” Men comprised more than two-thirds of the group. “The most common comorbidities were hypertension, sleep apnea and obesity,” Andrade said. “The patients were highly symptomatic.”
Primary endpoint results showed that freedom from any AF event rates were 57.1% in the ablation arm and 32.2% in the antiarrhythmic drug arm, for an absolute difference of 24.9 percentage points (HR = 0.48; 95% CI, 0.35-0.66; P < .001).
“The ablation group had a significantly lower recurrence than the antiarrhythmic drugs,” Andrade said. He added that the 24.9 percentage point difference corresponds to a number needed to treat of 4.
Ablation (89%) bested drug therapy (73%) in the secondary endpoint of freedom from symptomatic atrial tachyarrhythmia (HR = 0.39; 95% CI, 0.22-0.68; P < .001). “From the patient perspective, freedom from symptomatic arrhythmia is probably the most important outcome,” Andrade said.
Median percentage of time in AF was 0% in the ablation group (interquartile range [IQR], 0-0.08) and 0.13% in the drug therapy group (IQR, 0-1.6).
Similarly, ablation was superior to antiarrhythmic drug therapy in terms of freedom from symptomatic AF, freedom from any atrial tachyarrhythmia after multiple ablation procedures and freedom from symptomatic atrial tachyarrhythmia after multiple ablation procedures (P < .001 for all). “When you look at the remainder of the arrhythmia endpoints, you see a very consistent effect,” Andrade said.
With regard to quality-of-life parameters, although both interventions provided benefit as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score and the EQ-5D, “we again see a significant benefit toward ablation,” he said.
Serious adverse events were “no different between the groups,” according to Andrade, who reported these events in 3.2% of patients in the ablation group and 4% of those in the antiarrhythmic drug group (HR = 0.81; 95% CI, 0.25-2.59).
“The results of these three trials show that Medtronic cryoablation is a viable and even preferable option for patients with paroxysmal AF even prior to initiation of antiarrhythmic drug therapy,” Rob Kowal, MD, PhD, chief medical officer of the cardiac rhythm and heart failure division at Medtronic, told Healio. “Since AF is a progressive condition, early intervention treatment options become increasingly important — both for patients and the physicians treating them. With the positive findings of EARLY-AF, STOP AF First and Cryo-First, it is becoming increasingly clear of the paradigm shift in early intervention options, which will ultimately benefit patients diagnosed with AF.”
There were three phrenic nerve injuries and two pacemakers for bradycardia in the ablation group, whereas the drug therapy group had two each of wide-complex tachycardia and bradycardia, and one each of HF and syncope.
Any safety endpoint occurred in 9.1% of patients treated with ablation and 16.1% of those treated with antiarrhythmics (HR = 0.59; 95% CI, 0.29-1.21).
There were no significant differences with regard to health care utilization between the two arms.
“First-line ablation was associated with significant reductions in arrhythmia outcomes,” Andrade said.
Discussant Christine M. Albert, MD, MPH, chair of the department of cardiology in the Smidt Heart Institute at Cedars-Sinai Medical Center and president of the Heart Rhythm Society, said EARLY-AF adds “in big ways” to the body of knowledge on the use of ablation as first-line prevention of AF events.
“First, it is the largest trial,” she said. “Second, and very importantly, they used an implantable loop recorder to record their AF events. This is novel.”
The study also allowed assessment of AF burden, which showed it is possible to significantly reduce this outcome with both antiarrhythmic drugs and ablation, according to Albert. “But much more so with ablation,” she said.
One key component of the study was that an independent committee assessed AF events, according to Albert. Another was an independent committee to approve crossovers. “All of our ablation trials are always plagued by crossovers, and they actually had no patients who crossed over from the assigned group before primary endpoint,” she said. “Again, an excellent experiment.”
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Oussama Wazni, MD
The most important message from EARLY-AF and STOP AF First is that early ablation is really important. The other thing that we find is that in EARLY-AF even though loop recorders recorded more recurrence, symptomatic AF was much less with ablation. The findings are very encouraging. Of course, there was a big difference between ablation and antiarrhythmic drugs.
Once recurrent AF is diagnosed, and if not due to hyperthyroidism or some other acute illness, it should be aggressively managed. The sooner we intervene, the better the outcomes. It is time now for all of the societies to look at studies showing benefit of early ablation, including EARLY-AF, STOP AF First and EAST-AFNET 4, and consider changes to the guidelines and our practice. Medications have their side effects and have been shown to be marginally effective.
The issue of cost-effectiveness can come up, but I think that ablation, if studied, will also prove to be cost-effective in these patients.
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Andrade JG, et al. LBS.06: To screen or not to screen, and then what? Studies of detection and treatment of AF. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
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