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Variations in the pharmacological management of patients treated with carotid endarterectomy: a survey of european vascular surgeons
Eur J Vasc Endovasc Surg (2009) 38, 402e407
Variations in the Pharmacological Management ofPatients Treated with Carotid Endarterectomy:A Survey of European Vascular Surgeons
M. Hamish, M.S. Gohel, A. Shepherd, N.J. Howes, A.H. Dav
Imperial Vascular Unit, Charing Cross Hospital, London W6 8RF, UK
Submitted 19 December 2008; accepted 5 July 2009Available online 3 August 2009
Objectives: The peri-operative use of antiplatelet, anticoagulant and other drugs
for patients undergoing carotid endarterectomy (CEA) is unclear and consensus is lacking. This
study aimed to assess the current peri-operative practice of European vascular surgeons with
respect to antiplatelet and other medications for patients undergoing CEA.
Methods: Members of the Vascular Society of Great Britain & Ireland and European Society forVascular Surgery were invited to complete an online survey in March 2008. Surgeons wereasked about their preferences for the peri-operative administration of antiplatelet, statinand other medications for patients undergoing carotid endarterectomy.
Results: Partial or complete responses were received from 399/650 (61.4%) surgeons witha collective annual throughput of >11500 CEA procedures. For symptomatic and asymptomaticpatients, 20/392 (5%) and 47/392 (12%) of surgeons would stop aspirin before surgery and 170/392 (43%) and 217/392 (55%) of surgeons would stop Clopidogrel prior to CEA. Of surgeons whowould stop Clopidogrel, 84/170 (49%) and 124/217 (57%) would do so >7 days before surgeryfor symptomatic and asymptomatic patients respectively. 12/393 (3%) surgeons would prescribeone 75 mg dose of Clopidogrel on the evening before surgery. Intra-operative Dextran was usedselectively by 40/395 (10%). Only 78/393 (20%) would delay surgery to commence a statin.
Intra-operatively, 348/394 (88%) used intravenous heparin, which was reversed routinely by47/348 (13%) and selectively by 60/348 (17%).
Conclusions: There appears to be broad consensus between vascular surgeons in the pharmacolog-ical management of patients undergoing carotid endarterectomy, although some variations do exist.
Further clinical studies may help clarify the optimum management strategy in this patient group.
ª 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Numerous large randomized studies including the North
1078-5884/$36 ª 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
(NASCET),the European Carotid Surgery Trial (ECST)and
the Asymptomatic Carotid Surgery Trial (ACST)haveevaluated the effectiveness of carotid endarterectomy in
Partial or completed questionnaires were received from 399
patients with significant internal carotid artery stenosis.
of the 650 (61.4%) Vascular Surgeons invited to participate.
These have demonstrated a significant reduction in the risk
Published email addresses were inaccurate for 98/650
of death or disabling strokes for patients randomized to
(15.1%) and 153/650 (23.5%) did not respond. A total of 284
surgery in comparison to those in the non-surgical arms.
responses were received after the initial invitation email and
However, consensus is lacking on the peri-operative
a further 115 responses were received after the reminder
prescription of antiplatelet, cholesterol lowering or other
email. The combined throughput of those who completed
medications for patients requiring carotid endarterectomy
the survey was >11,500 CEA procedures per annum. Of the
(CEA). A recent meta-analysis reported that aspirin was
361 respondents that answered the specific question, 239
protective in most patients at increased risk of occlusive
(66.2%) performed >20 CEA procedures per annum.
vascular events.Furthermore, large randomized clinical
Procedures were routinely performed using general anaes-
studies have demonstrated reductions in stroke and death
thesia by 178/362 (49.1%) whereas 151/362 (41.7 %) used
rates in patients treated with aspirin after
local anaesthesia and 33/362 (9.1%) used both techniques.
These findings suggest that a period of pre-operativeadministration followed by post-operative administration
of aspirin may have a protective effect in patientsundergoing CEA.
The vast majority of vascular surgeons surveyed would not
In order to maintain low complication rates following
stop aspirin prior to carotid endarterectomy for symptom-
CEA, multiple components of the pre, intra and post-
atic or asymptomatic patients (372/392 [94.8%] and 345/
operative care must be carefully managed. Tsurgical tech-
392 [88.0%] respectively) ). Of the 47 respondents
nique and appropriate use hese factors include patient
that would discontinue aspirin (including 20 who would do
selection, assessment of cardiac risk factors, precise blood
so for patients with symptomatic and asymptomatic carotid
coagulation and other medications. The aim of this study
surgery and 14/47 (29.8%) would stop aspirin for at least 7
was to evaluate the use of peri-operative antiplatelet,
days. When asked about pre-operative Clopidogrel use,
anticoagulant and other medications amongst European
170/392 (43.3%) and 217/392 (55.3%) of surgeons would
stop Clopidogrel before surgery for symptomatic andasymptomatic patients respectively. Of surgeons who would
stop Clopidogrel, 84/170 (49.4%) and 124/217 (57.1%) woulddo so >7 days before surgery for symptomatic and asymp-
An email invitation to complete an online 16-part ques-
tomatic patients respectively. For both aspirin and Clopi-
tionnaire was sent to all listed members of the European
dogrel, surgeons were more likely to stop antiplatelet
Society of Vascular Surgery (ESVS) and the Vascular Society
medications prior to surgery for asymptomatic rather that
of Great Britain and Ireland (VSGBI). The societies were not
involved in the design of the study. Questions relating to
the pre, peri and post-operative pharmacological manage-
A high proportion of respondents stated that they would
ment of patients undergoing CEA were devised by the study
continue Dipyridamole prior to surgery for symptomatic or
authors Questions related to pre-operative
asymptomatic disease; 247/250 (98.8%) and, 211/250
antiplatelet, anticoagulant and statin use; intra-operative
(84.4%) respectively. A total of 285/392 (72.7%) and 389/
heparin, dextran, protamine and dexamethasone use and
392 (99.2%) of respondents would stop Warfarin prior to CEA
post-operative antiplatelet use. The initial invitation email
Interestingly, 12/393 (3.0%) of surgeons would
was sent in March 2008 and a reminder email was sent in
prescribe a pre-operative 75 mg dose of Clopidogrel, the
June 2008. The questionnaire responses were anonymized
day before surgery. CEA would be delayed by surgeons
and only one response per email address was allowed by the
to give statin medication by 18/393 (4.9%) for symptomatic
online academic survey software (Bristol Online Surveys).
patients and 60/393 (15.2%) for asymptomatic patients.
All complete and partially completed responses wereincluded in the analysis and the number of completed
responses received for each question is presented as thedenominator. Statistical analysis was performed using the
Only 13/394 (3.2%) surgeons would give intra-operative
Chi Square test (SPSS v16.0, Chic, IL, USA).
pooled platelets if the patient was on dual antiplatelet
Numbers of respondents who would stop antiplatelet and anticoagulant medications prior to CEA
therapy (aspirin and Clopidogrel or Dipyridamole). The
TIA.Despite these studies, 5e12% of surveyed surgeons
majority of surgeons would routinely give heparin prior to
would stop aspirin and more than half would stop Clopidogrel
arterial clamping (348/394 [88.3%]), but only 47/348
pre-operatively. Clearly, further clinical studies demon-
(13.5%) would routinely reverse the heparin and 60/348
strating clear benefits are needed before dual antiplatelet
(17.2%) would reverse it selectively. Regarding blood pres-
therapy is widely adopted by surgeons performing CEA.
sure management during surgery, 245/394 (62.1%) would
Interestingly, a small proportion of surgeons would delay
aim to maintain normotension during CEA, although 97/394
carotid endarterectomy for a week or more in order to give
(24.6%) would aim to keep patients hypertensive. Dextran
statins. The use of statins has been suggested as a potential
was routinely prescribed by 40/397 (10.0%) of respondents
method of plaque stabilization prior to CEA, a hypothesis
and selectively (based on transcranial Doppler readings) by
supported by histological studies.Clinical studies have
a further 27/397 (6.8%). Dexamethasone was used routinely
also shown lower rates of adverse events in patients taking
or selectively by a minority of respondents; 14/363 (3.8 %)
statins prior to Interestingly, large studies have sug-
gested that this benefit is greatest in symptomatic ratherthan asymptomatic In a retrospective study,
McGirt et al. suggested that peri-operative statin use (atleast for one week before surgery and one month after)
Among the surgeons who would discontinue antiplatelet
may reduce the incidence of cerebrovascular events and
drugs, 18/20 (90.0%) would restart aspirin and 131/189
mortality among patients undergoing A further study
(69.3%) would restart Clopidogrel on first day post-opera-
demonstrated that 4 weeks of treatment with atorvastatin
resulted in significant local and systemic reductions ininflammatory mediators in patients undergoing carotid
endarterectomy. These findings suggest that statins mayreduce atherosclerotic plaque inflammation and potentially
This survey demonstrated that the majority of European
delay or prevent plaque rupture.These observations are
Vascular Surgeons who responded would continue aspirin,
intriguing, but more definitive studies are needed before
but most would stop other antiplatelet and anticoagulant
broad recommendations can be agreed. A strategy of
medications prior to carotid endarterectomy. Moreover,
delaying CEA for the administration of statins may seem
most respondents would use heparin intra-operatively, aim
logical in asymptomatic patients, but may be detrimental in
to maintain normal blood pressure during surgery and restart
symptomatic patients. The increasingly widespread use of
antiplatelet medications on the first post-operative day.
statins in high-risk populations is likely to mean that the
Although a broad consensus was seen, it is worth noting that
vast majority of patients requiring CEA will already be on
some variation in the clinical practice of European Vascular
Surgeons was demonstrated in this study, highlighting the
The maintenance of hypertension (around 20% above
scarcity of level 1 evidence or clinical guidelines in this area.
pre-operative systolic pressure) during CEA may be justified
The decision to continue to stop antiplatelet and anti-
by fears of ‘watershed’ stroke during carotid cross-
coagulant drugs requires the clinician to evaluate the risks
clampingand evidence from patients undergoing awake
and benefits for each individual patient and balance the risks
CEA where neurological deficits may be reversed by
of bleeding and thrombosis. In a study that investigated the
elevation of arterial pressure.However, most clinicians
use of 75 mg of Clopidogrel in addition to 150 mg of aspirin,
would agree that absolute values or targets should be
a significant reduction in peri-operative emboli was seen
viewed as guidelines only and adapted to individual
without any increase in bleeding complications or blood
patients,particularly as augmentation of arterial pressure
transfusion.A recent systematic review found that the risk
may be associated with increased risks, including a higher
of peri-operative stroke among those receiving antiplatelet
incidence of myocardial infarctionand intracerebral
agents was significantly reduced in comparison with the risk
haemorrhage.Dextran is thought to prevent platelet
for those not receiving antiplatelet therapy, but that the
adherence to the endarterectomy site, although its role in
risks of peri-operative death in the two groups were not
CEA remains unclear. There is evidence to suggest that
significantly Another study suggested that
dextran 40 may reduce the incidence of post-operative
a single 75-mg dose of Clopidogrel, taken the evening before
emboli and stroke (assessed using transcranial
carotid endarterectomy, may reduce post-operative embo-
Corticosteroids (dexamethasone 24e40 mg/day in divided
lisation, a marker of thrombo-embolic Moreover,
doses) may reduce vasogenic cerebral oedema, but their
a recent meta-analysis suggested that the use of Dipyr-
routine use in treatment of ischaemic strokes is
idamole in combination with aspirin may be the best choice
for secondary prevention of vascular events after stroke or
patients treated with CEA are scarce, although a recent
Time to restarting antiplatelet and anticoagulant medications
randomized trial did suggest that dexamethasone may be
medications, which is an increasingly common clinical
effective in reducing the incidence of temporary cranial
scenario. In conclusion, there appears to be broad
consensus between vascular surgeons in the use of anti-
We recognize that survey studies are often limited by
platelet and statins for patients undergoing carotid endar-
poor response rates. The response rate in this study was
terectomy, although some variations do exist. Only by
only 61%, although this compares favourably with other
establishing evidence-based guidelines can we achieve
similar Moreover, it is likely that a large number
greater consistency of treatment for this patient group.
of surgeons (not members of ESVS or VSGBI) were notincluded and heterogeneity in clinical practice acrossEurope may limit the generalisability of this study. Another
limitation of this study was the lack of questions on themanagement
stop the following medications prior to CEA:
c. Clopidogrel one dose pre-operatively only
d. Clopidogrel 48 h pre-operativelye. Clopidogrel 7 days pre-operatively
If a patient is not taking a statin would you
delay endarterectomy in order to start one?
If you do not routinely stop antiplatelet medication,
would you routinely give patients additional platelets?
c. Yes but only if the patient is on Clopidogrel
d. Yes but only if the patient is taking aspirin and Clopidogrele. Yes if the patient is taking aspirin and Dipyridamole
Intra operatively, how best describes the
patients’ systolic blood pressure before
d. Selectively based on clinical assessmente. No Answer
Peri-operatively do you give dexamethasone?
d. Selectively based on clinical assessmente. No Answer
medication prior to surgery, when do you restart it?
On average how many carotid endarterectomy
What type of anaesthesia do you use for the
majority of your carotid endarterectomy procedures?
Which antiplatelet medications do you routinely
prescribe for patients requiring carotid endarterectomy?
8 Payne DA, Jones CI, Hayes PD, Naylor AR, Goodal AHI. Thera-
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GINA SONG UNC Eshelman School of Pharmacy ♦ (919)966-1622 ♦ firstname.lastname@example.org EDUCATION University of North Carolina , Chapel Hill, NC Present Eshelman School of Pharmacy Division of Pharmacotherapy and Experimental Therapeutics Ph.D. student University of Minnesota , Minneapolis, MN May 2005 – May 2008 Ewha Women’s University, Seoul, Republ