4. Discussion
The main finding from our updated study that includes contemporary
ablation tools is that catheter ablation for pulmonary vein isolation is
more effective than AAD as initial therapy for pAF in reducing AT
recurrences after the initial blanking period to 1-2 years. In addition,
this benefit with ablation was the same in both cryoablation and
radiofrequency ablation with similar relative reductions in risks.
Despite the augmented efficacy for reduction in AF recurrences with
catheter ablation, we did not observe a significant increase in any
adverse events in these patients compared to AAD therapy.
In this updated meta-analysis of RCTs, we found two recently published
RCTs that add to prior summary work in this area. The new search
resulted in a total of 5 RCTs to date. The 2 newly added RCTs, EARLY-AF
and STOP AF First, used cryoballoon ablation for pulmonary vein
isolation, which is different from the previous 3 RCTs that all used
radiofrequency ablation. Evidence from the Cryoballoon or Radiofrequency
Ablation for Paroxysmal Atrial Fibrillation (FIRE AND ICE) trial
suggested that treatment efficacy of cryoballoon ablation was
non-inferior to the more traditional radiofrequency ablation in
drug-refractory pAF [22]. However, the efficacy of cryoablation in
treatment-naïve pAF was still unclear, especially when compared directly
to AAD or radiofrequency ablation. The EARLY-AF trial and the STOP AF
First trial were the first RCTs to compare cryoablation to AAD as an
initial therapy for pAF. This gave us opportunity to indirectly compare
the two ablation strategies as initial treatment for pAF. As shown in
figure 1, the pooled HR for the cryoablation subgroup (figure 1A) was
similar to the pooled HR for the radiofrequency ablation subgroup
(figure 2). However, as these pooled data are derived from a
retrospective comparison, further prospective RCTs that directly
comparing the two techniques are needed to confirm this finding or
investigate if one may be preferable over the other for treatment naïve
pAF compared to AAD.
The included studies in our meta-analysis demonstrated a significant
reduction in AT recurrence at 1-2 years with a similar effect size. The
EARLY-AF trial and the RAAFT-2 trial reported HRs for AT recurrence. In
the MANTRA-PAF trial, the RAAFT-1 trial, and the STOP-AF First trial,
the authors did not report HRs for AT recurrence. Nevertheless, the
authors provided sufficient raw data for us to calculate HRs as
described in the methods section. The HRs from each study are shown in
figure 1 along with the pooled HR.
The study designs are similar among the 5 included RCTs. Inclusion and
major exclusion criteria are shown in table 1. Briefly, all studies
included strictly symptomatic pAF without prior use of class I and III
AADs. Major exclusion criteria being used in all studies were previous
ablation or surgery of the left atrium, reversible causes of AF,
structural or valvular heart disease, a left atrial diameter
>5-5.5 cm, a left ventricular ejection fraction
<35-45%, NYHA class III-IV heart failure. For AT outcome
measurements, all studies reported using a blanking period of 60-90 days
following the ablation with follow up of patients up to 1-2 years. Three
studies used radiofrequency ablation and two studies used cryoablation
as described in table 1. The subgroup analysis by ablation method is
shown in figure 2A and 2B that demonstrates similar results between the
2 ablation techniques. The consistency and similarity in study design
likely contributed to the absence of heterogeneity (I=0.0%) in our
analysis, which indicates that our result is robust.
Atrial arrhythmia type as endpoint differs slightly among the included
studies. The MANTRA-PAF trial and the RAAFT-1 trial considered only AF
as the clinical endpoint for recurrence. For the EARLY-AF trial, the
RAAFT-2 trial, and the STOP AF First trial, authors consider either of
AF, atrial flutter, and atrial tachycardia as the clinical endpoint. It
is likely due to the difference in definition of endpoint that the
MANTRA-PAF trial and the RAAFT-1 trial reported lower recurrence rates
than the other 3 RCTs, except for the AAD group from the RAAFT-1 trial
that had a comparable recurrent rate to the other 3 RCTs.
Table 3 shows a summary of the adverse events. Overall, the adverse
event rates were low, and not many specific adverse events of interest
occurring in either of the ablation group or AAD group in some studies.
We were able to perform a meta-analysis on several adverse events
including cerebrovascular accident, PV stenosis, pericardial effusion or
tamponade, bradycardia requiring pacemaker, syncope, acute coronary
syndrome, DVT or PE, all of which were statistically similar between the
two groups. For other adverse events including mortality, phrenic nerve
injury, esophageal-related complications, and perforation, there was
only 1 study available for a meta-analysis for each outcome. The
individual ORs for these adverse events also did not demonstrate
significant differences between the two groups. Nevertheless, these
findings must be interpreted with caution as this could be from
inadequate power from the extremely low number of events which subjects
this sub-analysis to risk of a type II error.