Asymptomatic carotid artery stenosis is an atherosclerotic disease which involves
the carotid artery and features no history of ischemic stroke or transient ischemic
attack. The prevalence of asymptomatic carotid artery stenosis in the general population
is known to range up to 3.1% which is not insignificant.1) In current clinical practice,
medical treatment (MT), carotid endarterectomy (CEA), and carotid artery stenting
(CAS) are all available. However, according to 2017 European Society of Cardiology
(ESC) guidelines,2) there is no class I recommendation for treatment modality in asymptomatic
carotid artery disease due to weak consistency among the relevant data. More importantly,
there is no evidence which compares efficacy between MT and CAS, which are both less
invasive, with respect to being included in the guidelines. Therefore, recommendations
for asymptomatic carotid stenosis are inevitably indirect at the current time. Ideally,
randomized trials are required to compare the efficacy and safety of MT, CEA, and
CAS. But considering the ethical and realistic limitations, gathering as much evidence
as possible and incorporating it in a large-scale analysis can be a way to overcome
the indirectness of previous evidence.
In this issue of Korean Circulation Journal, Roh et al.3) present a study which has
2 strengths. 1) By adopting a Bayesian cross-design, results of randomized controlled
trials (RCTs) and non-randomized controlled trials (NRCTs) were incorporated into
a large-scale analysis that compared MT, CEA, and CAS. 2) The Bayesian network meta-analysis
enabled indirect comparison between MT and CAS. The authors included 22 studies among
which were RCTs and NRCTs. A previous large-scale meta-analysis by Hadar et al.4)
included 41 studies on the MT of asymptomatic carotid artery stenosis. However the
meta-analysis did not compare the MTs to other invasive measures such as CEA and CAS.
Galyfos et al.5) recently pooled 10 randomized trials and evaluated 8,711 patients
with respect to asymptomatic carotid artery stenosis treatments and compared MT, CEA,
and CAS. However, the authors could not compare MT and CAS in head-to-head manner,
because there was no study that directly compared those treatment modalities. To the
best of our knowledge, the study by Roh et al.3) is the largest scale study to investigate
the efficacy and safety of MT, CEA, and CAS in a head-to-head manner.
With respect to a comparison of CAS and CEA, Roh et al.3) demonstrated similar results
seen in previous studies. The periprocedural stroke risk increased in CAS compared
to CEA and periprocedural myocardial infarction risk increased or was similar in CAS
compared to CEA. This result is in line with the 2017 ESC guidelines, which recommends
CEA as the first treatment modality to be used in standard patients. The results of
the MT and CAS comparison that demonstrated a trend for lower risk in CAS can be interpreted
as CAS is better compared to MT in patients with asymptomatic carotid artery stenosis.
However, as the authors clarified in their discussion, most analyzed studies regarding
MT are mostly outdated. Previous studies which assessed MT for asymptomatic carotid
artery stenosis report improved efficacy as the publication date is more recent.6)
7) The efficacy of potent contemporary MT regimens may be clarified to some degree
in future studies such as the Carotid Revascularization and Medical Management for
Asymptomatic Carotid Stenosis Trial (CREST-2)8) and the Second European Carotid Surgery
Trial (ECST-2),9) which are future randomized trials.
Randomized trials which include a large number of patients will be essential to establish
more well-described and updated clinical practices and guidelines for asymptomatic
carotid artery stenosis. MTs for the disease include antiplatelet and lipid-modifying
agents, and stroke risk factor management. Those drugs and management protocols have
dramatically changed from the era of earlier studies on MTs.7) Single antiplatelet
therapy with aspirin has been the classic antiplatelet regimen. Other antiplatelet
drugs (i.e., clopidogrel, ticagrelor, or prasugrel) are supported by no data at the
current time. At this time, lipid-modifying agents include statins, ezetimibe, proprotein
convertase subtilisin/kexin type 9 (PCSK-9) inhibitors, icosapent ethyl, etc. The
2019 ESC/European Atherosclerosis Society (EAS) dyslipidemia guideline recommended
low-density lipoprotein cholesterol level should be targeted below 55 mg/dL in very
high risk patients. The accepted blood pressure goal has been changed since the Systolic
Blood Pressure Intervention Trial (SPRINT).10) These recently updated findings should
be assessed in future studies. Some of these questions may be answered by the above
mentioned CREST-2 and ECST-2, which are underway in North America and Europe, respectively.
There are limitations in the reviewed study that should be noted. The number of RCTs
was relatively small with respect to overcoming heterogeneous patient data which included
heterogeneous diagnosis modalities and stenosis severity.
Optimal treatment is a problem that has lingered for a long time, along with medical
technology advances and paradigm changes with respect to this condition. Future studies
may resolve some of the unanswered questions. However, there are pending questions
at the moment and precision medicine methods will be necessary for decision making
in asymptomatic carotid artery stenosis.