DISCUSSION
Optimal antithrombotic therapy after LAAC with the Watchman occluder
remains uncertain. This study aimed to investigate the efficacy and
safety of a 3-month dual antiplatelet therapy (DAPT) after LAAC, as well
as the risk factors that could affect the net clinical benefit and
bleeding events. The results strongly suggest that in patients who
underwent LAAC with the Watchman occluder, 3-month DAPT is associated
with fewer bleeding events.
A suitable bridging antithrombotic protocol is essential to prevent
thromboembolic complications during the endothelialization period of
LAAC devices. The strategy of ACT adopted in the PROTECT-AF and PREVAIL
trials 9, 10 has the most solid scientific evidence
for effectiveness, but it limited to patients eligible for OAC. In
contrast to clinical trials, the bridging protocols are very
heterogeneous in everyday clinical practice 8. The
most commonly used strategy, although it is only based on observational
evidence, is DAPT directly after LAAC for a limited period (6 weeks to 6
months), followed by antiplatelet monotherapy, and the regimen
prescribed in the PROTECT-AF and PREVAIL trials was less adopted8.
In the present post hoc study of 524 patients who underwent successful
LAAC with the Watchman occluder and with 12 months of follow-up, 3-month
DAPT regimen was compared with the regimen of 45-day ACT plus aspirin
followed by 4.5-month DACT (totally 6 months) after LAAC. Despite the
fact that the investigated population in the DAPT group was a high-risk
patient group (mean age, 78.4±7.2;
CHA2DS2-VASc, 4.8±1.5; HAS-BLED,
3.3±0.7), no significant difference was found in primary efficacy and
safety outcomes and net clinical benefit events between the two type of
antithrombotic regimens. The less aggressive bridging antithrombotic
regimen with DAPT did not reduce the net clinical benefits after 12
months. Age ≥75 years was independently associated with an increased
risk of decreased clinical net benefits while bridging antithrombotic
therapy was not a significant risk factor after multivariable analysis.
Those findings confirm the results of the EWOLUTION registry and another
propensity-matched study based on several Watchman registries, which
demonstrated similar efficacy and safety of both ACT and DAPT regimens11, 12.
Before device endothelialization, DRT and ischemic stroke are dreaded
complications. On the other hand, bleeding events, due to
anticoagulation, play a substantial role after LAAC. Of note, the rate
of the overall bleeding events was significantly higher in the ACT group
than in the DAPT group, although no differences in MB during follow-up
were observed. More patients under the ACT treatment suffered from
CRNMB). We found that the ACT regimen was an independent risk factor for
bleeding events. Despite differences between studies, whether about the
characteristics or definitions of outcomes, prior history of bleeding as
well as elderly people >75 years were identified as
independent risk factors for bleeding events 7. In the
present study, there was only a trend toward an association between
these two factors with bleeding events. This is likely due to the low
numbers of patients. Consistent with the EWOLUTION trial, in both
treatment arms, all fatal and most of the bleeding events occurred
during the most aggressive phase of antithrombotic therapy12, 14.
Less aggressive antithrombotic postprocedural LAAC therapies would be
appealing, potentially causing fewer bleeding complications, which, to
this date, is the most common and challenging complication after LAAC25. The current Watchman instructions for use
recommend an antithrombotic regimen tailored to each patient’s
individual stroke and bleeding risk, allowing either a 3-months DAPT or
an OAC. Several studies investigated various antithrombotic schemes
following LAAC. The real-world ASAP registry evaluated a 6-months DAPT
in 150 patients undergoing LAAC with the Watchman and reported a low
annual rate of ischemic stroke of 1.7% 26. Another
all-comer single-center registry documented the same rate of ischemic
stroke (1.7%) with a short-term DAPT for 6 weeks following LAAC with
Amplatzer and Watchman devices in 298 patients 7.
Furthermore, it revealed a low annual major bleeding rate of 3.9%. Two
registries with 110 and 76 patients investigated a SAPT after LAAC with
Amplatzer devices 27, 28. They reported a slightly
higher stroke rate of 2.3% and 4.0%, as well as a very low bleeding
rate of 2.1% and 1.3%. Lastly, the 3-months results of the EWOLUTION
registry found no relevant differences in DAPT, VKA, NOAC, SAPT, or no
therapy with regard to effectiveness and safety. Interestingly, NOAC
therapy had the lowest event rate, numerically 14.
The annual rates of ischemic stroke and MB in the present study were
similar for both treatment arms while slightly higher than the
aforementioned registries. This could partially be explained by higher
risks for ischemic stroke and MBs, as depicted by the relatively high
CHA2DS2-VASc (4.8±1.5) and HAS-BLED scores (3.3±0.7), and a shorter
follow-up duration with most events occurring in the early phase after
device implantation. In the ACT group, MBs, including three fatal
events, were observed during early follow-up and occurred predominantly
in patients with a high HAS-BLED score and prior bleeding events. This
observation was also made in the PROTECT and PREVAIL studies, which used
the ACT regimen and documented a relatively high estimated annual
bleeding rate of 10.5% 9, 10. In the long term, at
five years, the overall annual risk of MB was reduced to 3.1%29.
The rate of major periprocedural complications (3.4%) in the present
study was in line with other studies (PREVAIL study: 4.2%9, CAP registry: 4.1% 30, EWOLUTION
registry: 2.7% 31). TEE at follow-up revealed a low
rate of major peri-device leaks for both groups, which is comparable to
that reported in the EWOLUTION registry (0.7%) 31. In
the ACT group, one case of TIA was documented in a patient with a major
peri-device leak. An association of peri-device leaks and the occurrence
of thromboembolic events has not been found yet 32.
The rate of DRT did not differ between the treatment arms. In contrast
to this finding, the propensity-matched analysis of ACT and DAPT
observed more DRT in the DAPT group 11. All patients
with major peri-device leaks and DRT were switched to OAC. In the ACT
group, two ischemic events were associated with DRT during follow-up.
Nevertheless, neither peri-device leak nor DRT was associated with
clinical adverse events during follow-up in the DAPT group. This is
likely a chance finding due to the small sample size of the study, low
event rate, and different frequency for TEE follow-up. The impact of DRT
on ischemic stroke is well documented in several studies32-34.
All-cause mortality in the DAPT group was considerable and higher than
in the ACT group. This is probably due to the slightly higher age, rates
of coronary heart disease and a significantly poorer left ventricular
function in the DAPT group compared with the ACT group. Nonetheless, the
DAPT subgroup of the EWOLUTION registry also reported a death rate of
10%, which reflects the elderly, fragile, and multimorbid LAAC patient
population in European countries. Individual patient’s aspects like
comorbidities, quality of life, and residual life expectancy should be
taken into account when considering LAAC in octogenarians.