SCIENTIfIC RepoRTS | (2018) 8:4458 | DOI:10.1038/s41598-018-22356-z
Systematic review and network
meta-analysis of treatment
strategies for asymptomatic carotid
, Iain Roy
, Stavros A. Antoniou
, Francesco Torella
George A. Antoniou
We aim to perform a systematic review and meta-analysis to investigate outcomes of treatment
strategies for asymptomatic carotid disease. We searched electronic bibliographic sources (MEDLINE,
EMBASE, CINAHL and CENTRAL) to identify randomised controlled trials (RCT) reporting comparative
outcomes of carotid endarterectomy (CEA), carotid stenting (CAS) and best medical therapy (BMT) in
asymptomatic carotid disease. We performed pairwise meta-analysis applying random or xed-eects
models and reported the results as the odds ratio (OR) or risk dierence (RD) and 95% condence
interval (CI). We also performed a network meta-analysis and obtained a hierarchy of the competing
interventions using rankograms and the surface under the cumulative ranking curve and mean ranks.
Stroke and death within 30 days and during follow up were the primary outcome endpoints. Eleven
RCTs were identied reporting a total of 8,954 patients. Compared to BMT, CEA reduces the odds of
long-term mortality (OR 0.70, 95% CI 0.43, 1.12) and ipsilateral stroke (OR 0.59 95% CI 0.50, 0.71).
Network meta-analyses league table demonstrated that BMT is superior to CEA and CAS in terms of
perioperative stroke risk and mortality. CEA is the preferred method to reduce the long-term risk of
ipsilateral stroke and mortality for patients with asymptomatic carotid disease.
Stroke is the second leading cause of disability in Europe aer ischaemic heart disease and the sixth leading cause
. In Europe, the annual cost of stroke is an estimated €27 billion: €18.5 billion for direct costs and
€8.5 billion for indirect costs
Carotid atherosclerosis is a signicant cause of ischemic stroke and transient ischemic attack (TIA)
optimal treatment for patients with asymptomatic carotid disease remains controversial with no clear consensus
to recommend the best therapy for them. Carotid endarterectomy (CEA) has been suggested to be superior in
preventing stroke compared to medical therapy alone in asymptomatic patients with >70% stenosis
stenting (CAS) has emerged as a therapeutic alternative to endarterectomy for the treatment of severe carotid
stenosis. e results of randomized trials comparing stenting and endarterectomy have been conicting
In 2011, the American Heart Association (AHA) published its updated guidelines on the role of CEA and
CAS in asymptomatic patients
. Its recommendations were based on two landmarks randomised clinical trials
published in 1995 and 2004
. However, medical therapy in these trials was not comparable with current stand-
ards. Medical therapy for stroke prevention has improved since these original trials, with more widespread use
of statins, more active lowering of blood pressure and more eective antiplatelet regimes. More recent data from
the Oxford Vascular Study (OXVASC) demonstrate a stroke risk of only 0.3% per year attributable to ipsilateral
asymptomatic carotid stenosis treated with best medical therapy (BMT) alone
In view of the improving medical therapy for stroke prevention with more widespread use of statins, more
active lowering of blood pressure and more eective antiplatelet regimes, there is currently uncertainty as to
Liverpool Vascular and Endovascular Service, Royal Liverpool University Hospital, Liverpool, UK.
Ageing and Chronic disease, University of Liverpool, Liverpool, UK.
Department of Surgery, University Hospital of
Heraklion, University of Crete, Heraklion, Greece.
School of Physical Sciences, University of Liverpool, Liverpool,
Department of Vascular and Endovascular Surgery, The Royal Oldham Hospital, Pennine Acute Hospitals NHS
Trust, Manchester, UK. Correspondence and requests for materials should be addressed to M.B. (email: mohamed.
Received: 18 September 2017
Accepted: 21 February 2018
Published: xx xx xxxx