From the American Venous Forum

Clinical response to combination therapy in the

treatment of varicose veins
R. Gregory Conway, MD, MS,a Jose I. Almeida, MD,b Lowell Kabnick, MD,c Thomas W. Wakefield, MD,d
Andrea G. Buchwald, PhD,e and Brajesh K. Lal, MD,a Baltimore, Md; Miami, Fla; Morristown, NJ; Ann Arbor, Mich; and
Denver, Colo

ABSTRACT
Background: Varicose vein ablation procedures are being performed with increasing frequency; however, there is a lack
of consensus on the relative efficacy of combined treatment of saphenous incompetence and symptomatic varicosities
vs a staged approach. In this study, we examined the impact on symptom severity when a procedure to eliminate
varicosities was added to standard endovenous saphenous ablation.
Methods: The Varicose Vein Module of the American Venous Registry was established by the American Venous Forum in
2010 and collected data from 48 physicians during a 5-year period. We analyzed patients with Clinical, Etiology, Anatomy,
and Pathophysiology (CEAP) C2 disease severity and without prior treatment. Combination therapy (CT) was defined as
the use of a procedure directly addressing visible varicosities (stab phlebectomy or injection of sclerosant into varicosity)
combined with endovenous saphenous vein ablation. Unimodal therapy (UT) was defined as endovenous saphenous vein
ablation alone (radiofrequency or laser). Change in symptom severity was assessed by the pretreatment and 1-month
follow-up Venous Clinical Severity Score (VCSS). Univariate statistics compared the CT and UT groups, with P values
obtained using the Student t-test or Pearson c2 test as appropriate. A multivariable linear regression model assessed the
association of CT with the change in VCSS.
Results: There were 526 patients included for analysis (UT, 97; CT, 429). UT patients were more likely to be white (85.6% vs
62.7%; P < .001), had a higher initial VCSS (6.71 vs 5.07; P < .001), and were assessed at an earlier follow-up visit (28.9 days
postoperatively vs 33.3 days; P < .001). Compared with UT, CT was associated with an additional half-point reduction in
VCSS on univariate analysis (
3.71 points for UT vs
4.20 for CT; P ¼ .13). After treatment, CT was associated with signifi-
cantly lower scores on the pain and varicose vein components of the VCSS (pain: 0.31 for UT vs 0.07 for CT [P ¼ .0008];
varicose veins: 0.47 for UT vs 0.03 for CT [P < .001]). On the multivariable model, after adjustment for white race, day of
follow-up, age group, and initial VCSS, CT was associated with an additional reduction in VCSS of 1.52 points compared
with UT (P ¼ .002).
Conclusions: Invasive treatment of C2 chronic venous insufficiency improves symptom severity. Whereas treatment of
venous reflux is essential to address venous symptoms, our results suggest that patients further benefit from additional
direct treatment of varicosities. For selected patients, CT may present a more effective treatment strategy than saphe-
nous ablation alone. (J Vasc Surg: Venous and Lym Dis 2019;-:1-8.)
Keywords: Varicose vein; Endovenous ablation; Phlebectomy; Venous Clinical Severity Score

Chronic venous insufficiency is highly prevalent,
affecting a large proportion of adults in the United
States.1 Characterized by the presence of axial venous
reflux in the lower extremity, manifestations include spi-
der veins (64% of patients), varicose veins (29% of
patients), and skin changes (8% of patients).1 Varicose
veins are a common reason for patients to seek
treatment, and currently there are several accepted
treatment modalities to eliminate the underlying truncal
incompetence seen in the majority of cases. These
include endovenous ablation (using laser or radiofre-
quency energy), sclerotherapy, and open surgery (saphe-
nous vein stripping, stab phlebectomy) as well as
combinations of these techniques.
The invasive treatment modalities can be categorized
into those that treat the axial venous reflux (endovenous
saphenous vein ablation, saphenous vein stripping) and
those that treat the varicosities directly (stab

From the Division of Vascular Surgery, University of Maryland School of Medi-
cine, Baltimorea; the Miami Vein Center, Miamib; the Kabnick Vein Center,
Morristownc; the Section of Vascular Surgery, University of Michigan, Ann
Arbord; and the Department of Environmental and Occupational Health, Uni-
versity of Colorado School of Public Health, Denver.e
Funding was provided to B.K.L. by VA Merit Award RX000995-04.
Author conflict of interest: L.K. has been paid a consulting fee and royalties by
AngioDynamics.
Presented at the Thirty-first Annual Meeting of the American Venous Forum,
Rancho Mirage, Calif, February 19-22, 2019.
Correspondence: Brajesh K. Lal, MD, Division of Vascular Surgery, University of
Maryland Medical Center, 22 S Greene St, S10B00, Baltimore, MD 21201
(e-mail: blal@som.umaryland.edu).
The editors and reviewers of this article have no relevant financial relationships to
disclose per the Journal policy that requires reviewers to decline review of any
manuscript for which they may have a conflict of interest.
2213-333X
Copyright Ó 2019 by the Society for Vascular Surgery. Published by Elsevier Inc.
https://doi.org/10.1016/j.jvsv.2019.10.015

1
2 Conway et al
phlebectomy, injection of sclerosant into the varicosity).
The body of literature indicating effectiveness of both
endovenous and open techniques for the treatment of
varicose veins is well established.1-8 The evidence sup-
porting the combination of open surgical and endove-
nous techniques is limited, however, despite the
common clinical practice of combining therapies.9-11
The clinical practice guidelines for the care of patients
with varicose veins and associated chronic venous dis-
eases, released in 2011 by the Society for Vascular Surgery
and the American Venous Forum, indicate that the com-
bination of surgical therapy with endovenous techniques
should be decided on the basis of the type of anesthesia
used. Specifically, if the patient is undergoing general
anesthesia for the endovenous procedure, it is recom-
mended that surgery be carried out in combination. If
local or regional anesthesia is used, it is acceptable to
delay surgery.12 Practically, however, therapeutic choice
may be largely dictated by reimbursement policies,
and there exists a lack of consistency with regard to
insurance policies on varicose vein treatment.13,14 Never-
theless, treatment decisions are best made on the basis
of contrasting the clinical outcomes achieved by
different approaches.
In this study, we investigate whether patients with C2
disease who receive the combination of a procedure
treating axial reflux (endovenous saphenous vein abla-
tion) and a procedure directly addressing varicosities
(stab phlebectomy, injection of sclerosant into varicosity)
are more likely to show clinical improvement than pa-
tients who receive endovenous saphenous vein ablation
alone. To assess this relationship, we aimed to determine
the difference in change in clinical symptoms between
the preoperative and follow-up Venous Clinical Severity
Scores (VCSS) for patients receiving their first treatment
of varicose veins. We hypothesized that patients
receiving a combination of endovenous ablation and
direct treatment of their varicosities are more likely to
experience symptomatic improvement.
METHODS
Study design, setting, and patients. After an exemption
was received from the University of Maryland Institu-
tional Review Board, a retrospective cohort study was
initiated through an analysis of data in the American
Venous Registry Varicose Vein Module (AVR-VVM). This
multicenter registry contains information of >7100 pa-
tients collected during a 5-year period, entered by 48
physicians at 46 centers. The AVR-VVM is a free registry
available to all physicians treating varicose veins. The
registry has been described in detail previously.15 In brief,
the registry contains comprehensive information on de-
mographics, therapeutic modality, perioperative treat-
ment, pretreatment disease severity, and post-treatment
disease severity. Deidentified patient information was
entered into the registry through a web-based interface
Journal of Vascular Surgery: Venous and Lymphatic Disorders
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ARTICLE HIGHLIGHTS
d
Type of Research: Multicenter retrospective analysis
of prospectively collected data from the American
Venous Registry Varicose Vein Module
d
Key Findings: Patients who underwent endovenous
saphenous vein ablation were compared with pa-
tients who had the addition of a varicosity-treating
procedure at the same time. At 1-month follow-up,
patients who had both therapies had a 1.52-point
greater reduction in Venous Clinical Severity Score,
with the trend persisting at 6 months.
d
Take Home Message: Procedures that directly treat
varicosities improve varicose vein symptoms. The
addition of such procedures should be considered
for patients undergoing endovenous saphenous
vein ablation.
by participating physicians, and a dedicated registry
administrator monitored data integrity. This is a self-
reported registry without adjudication, and participants
were encouraged to enter all of their procedures
consecutively.
In this study, patients who were identified as having no
prior varicose vein treatment were included in the
cohort. Patients were excluded if no axial reflux proced-
ure was performed or if data were missing on treatment
modality, pretreatment VCSS, or 1-month follow-up VCSS
because these variables were necessary for determina-
tion of exposure and outcome.
The initial cohort was examined for distribution of Clin-
ical, Etiology, Anatomy and Pathophysiology (CEAP) C
class among patients and was stratified by the use of
combined treatment or treatment of axial reflux alone.
The distribution of treatment modality between C class
groups was analyzed with a c2 test, and the final study
population was selected to maintain both sample size
and relative homogenicity of disease severity.
A subgroup analysis was performed of patients who
had follow-up information at 6 months to assess the
durability of treatment. All patients who were included
in the full 1-month follow-up cohort and who also had
follow-up information at 6 months were included in
this analysis.
Variable definitions. The primary outcome was change
in VCSS, defined as the total VCSS at the 1-month follow-
up minus the total VCSS before therapy. The VCSS is a
summation of 10 clinical symptom categories: pain,
edema, varicose veins, skin pigmentation, inflammation,
induration, active ulcer number, active ulcer duration,
active ulcer size, and use of compressive therapy. Each
symptom category is scored on a scale of 0 to 3, with
0 indicating no symptoms in a category and 3 indicating
severe symptoms. The total score ranges from 0 to 30,
Journal of Vascular Surgery: Venous and Lymphatic Disorders
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with a higher score indicating worse symptoms. The
specific scoring definitions and validation of this symp-
tom measurement tool have been previously
described.16 The 1-month follow-up VCSS was assessed at
postprocedure day 30 6 15 days, and the 6-month follow-
up VCSS was assessed at 180 6 15 days.
The primary exposure was the use of combination ther-
apy (CT), defined as the use of a varicosity-treating pro-
cedure in addition to an endovenous axial reflux-
treating procedure on the same lower extremity during
the same day. The endovenous therapies considered in
this analysis include endovenous laser ablation (EVLA),
radiofrequency ablation (RFA), and sclerotherapy; the
varicosity-treating procedures include stab phlebectomy,
hook phlebectomy, Trivex (LeMaitre Vascular, Burlington,
Mass), and sclerotherapy directed at the varicosity. The
use of CT was compared with unimodal therapy (UT),
defined as the use of only one of the three endovenous
axial reflux therapies specified before. Because the
AVR-VVM specifies procedural laterality, both the surgi-
cal and endovascular procedures were required to be
on the same lower extremity.
Covariates of interest included the patient’s age, sex,
race, initial VCSS severity, day of follow-up, and type of
endovenous axial reflux therapy used. The individual
components of the initial VCSS and follow-up VCSS as
well as the change in each individual component were
also analyzed with respect to the therapy used. These
covariates were chosen on the basis of known associa-
tion with severity of varicose vein symptoms or effect of
available treatments. For analysis, age was grouped into
four categories: <45 years, 45 to 54 years, 55 to 64 years,
and >64 years. Sex used standard categories. Race was
dichotomized into white or not white. Initial VCSS and
day of follow-up were analyzed as continuous covariates,
after verifying a reasonably linear relationship between
quartile levels of these covariates and change in VCSS.
Thrombotic complications were defined as the develop-
ment of a deep venous thrombosis (DVT) or endovenous
heat-induced thrombosis (EHIT) during the procedure.
Data analysis. All data were analyzed with SAS software
(version 9.4; SAS Institute, Cary, NC). Baseline patient
characteristics were determined for the following covari-
ates: age, sex, race, day of follow-up, mode of axial reflux
treatment, thrombotic complications, and initial VCSS
severity. The crude association between the use of CT
and the mean change in VCSS was established using
simple linear regression.
The individual VCSS components were assessed by
treatment type at the initial pretreatment visit and the
1-month and 6-month follow-up visits. The change in
these individual components was calculated on a per-
patient basis. Differences in pretreatment, follow-up, or
treatment-related change were assessed for the VCSS
components, with significance levels calculated using
Conway et al 3
t-tests. The ability to evaluate individual properties that
correspond to subtle changes in symptoms is considered
a strength of the VCSS, and analysis of changes in individ-
ual components has been performed in previous
studies.17,18
The independent associations of covariates with the
exposure of CT use was assessed. To determine whether
a statistically significant association between a covariate
and CT existed, Pearson c2 test was used to test for the
categorical variables of age group, sex, race, and initial
VCSS severity. For low-frequency categorical variables,
Fisher exact test was used when appropriate.
A P value <.1 was considered to be statistically significant
for identifying potential association between the corre-
sponding covariate and the use of CT.
Simple linear regression was used to determine the as-
sociation between the covariates of interest and the
outcome of mean change in VCSS. The specific variables
included age group, sex, race, day of follow-up, mode of
axial reflux treatment, and initial VCSS severity.
A P value <.1 was considered to be a statistically signifi-
cant indicator of potential association between the
covariate and the mean change in VCSS.
Adjustment for the potential confounders was first per-
formed on the crude analysis for the 1-month follow-up
change in VCSS. Any covariate that produced a $20%
change in the predicted effect of CT use on the mean
change in VCSS was included in the final model as a
confounder. Interaction product terms were used to
identify effect measure modification, and significant ef-
fect measure modifiers were included in the final model.
An additional model was computed controlling for initial
CEAP C class as an effect measure modifier.
Because of a substantial decrease in sample size at the
6-month follow-up time point, the analysis of the
6-month change in VCSS was controlled only for the
initial VCSS and an interaction term to avoid overfitting
of the model.
RESULTS
From 4758 recorded procedures for axial reflux treat-
ment with follow-up VCSS, 1031 had follow-up informa-
tion at 1 month. The distribution of C class severity
among the groups is shown in Table I. Patients with C2
and C3 disease composed >80% of the available proced-
ures. CT was used in 81.6% of patients with C2 disease vs
15.9% of patients with C3 disease (P < .001). Because of
significant differences in the use of UT and CT between
C2 and C3 disease severity, patients with C2 disease
were chosen for analysis. There were 526 patients who
had preoperative C2 disease and follow-up information
at 1-month and were included in the final cohort; 97 pa-
tients underwent UT and 429 patients underwent CT. Pa-
tients who underwent UT followed up earlier (28.9 days
for UT, 33.3 days for CT; P < .001), were more likely to be
white (85.6% vs 62.7% in CT; P < .001), and were more
4 Conway et al Journal of Vascular Surgery: Venous and Lymphatic Disorders
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Table I. Distribution of Clinical, Etiology, Anatomy, and From the 526 patients with 1-month follow-up, 69 had
Pathophysiology (CEAP) C class in the American Venous followed up at 3 months, 57 had also followed up at
Registry Varicose Vein Module (AVR-VVM)
6 months (UT; n ¼ 14), and 40 patients had followed up
CEAP Total UT (n ¼ 478 CT (n ¼ 553 at 12 months. For the subpopulation with 6-month
C class (N ¼ 1031) [46.4%]) [53.6%]) follow-up, patients who underwent UT were older
C0 6 (0.58) 5 (83.3) 1 (16.7) (78.6% older than 55 years vs 34.9% for CT; P ¼ .0344)
C1 5 (0.48) 4 (80.0) 1 (20.0) and were less likely to be female (50% vs 86.1% for CT;
C2 526 (51.0) 97 (18.4) 429 (81.6) P ¼ .0098). No significant difference was detected for
C3 302 (29.3) 254 (84.1) 48 (15.9) follow-up day, race, mode of axial reflux treatment, initial
C4 132 (12.8) 75 (56.8) 57 (43.2) VCSS, or change in VCSS on crude analysis.
C5 18 (1.75) 13 (72.2) 5 (27.8)
The overall and individual VCSS component scores
before and after treatment are displayed in Tables II
C6 42 (4.1) 30 (71.4) 12 (28.6)
and III, respectively. The mean initial VCSS was higher
CT, Combination therapy; UT, unimodal therapy.
Values are reported as number (%). in the UT group compared with the CT group (6.71 vs
P value <.001, c2 test. 5.07; P < .001). There was no statistically significant differ-
ence in the pretreatment VCSS component scores for
pain, varicose veins, pigment, or inflammation in
likely to have undergone RFA (73.2% vs 49.0%; P < .001). comparing UT and CT groups. However, fewer patients
Thirteen surgeons performed procedures in the UT who underwent CT reported edema as a significant
group, with 10 surgeons performing CT procedures. symptom before treatment. On univariate analysis, treat-
Seven surgeons performed procedures in both groups. ment resulted in an improvement (reduction) in VCSS in
Contributing surgeons performed a median of 2.0 pro- both treatment groups. Overall, patients who underwent
cedures (interquartile range, 5.0; UT vs CT, P ¼ .3840). CT experienced a 4.20-point reduction in VCSS (vs 3.71-
No statistically significant differences were seen between point reduction for UT). This finding approached but
the groups with respect to age, sex, or incidence of did not reach statistical significance (P ¼ .1289). However,
thrombotic complications (Table II). Complications patients who underwent CT experienced a significantly
were rare in this population of patients and included greater reduction in the varicose vein component score
two cases of EHIT, one DVT, one severe phlebitis, one compared with patients who underwent UT (UT,
1.59;
mild phlebitis, one infection, and one lymphocele. CT
1.88; P ¼ .0211). It is noted that there were 56 patients

Table II. Distribution of covariates in the cohort between unimodal therapy (UT) and combination therapy (CT) groups
Total (N ¼ 526) UT (n ¼ 97) CT (n ¼ 429) P value
Follow-up, days 32.5 (6.6) 28.9 (9.02) 33.3 (5.66) <.001a
Age, years .6105b
<45 172 (32.8) 28 (28.9) 144 (33.6)
45-54 124 (23.6) 27 (27.8) 97 (22.7)
55-64 135 (25.7) 23 (23.7) 112 (26.2)
>64 94 (17.9) 19 (19.6) 75 (17.5)
Female 383 (72.8) 69 (71.1) 314 (73.2) .6806b
White 352 (66.9) 83 (85.6) 269 (62.7) <.001b
Mode of axial reflux treatment <.001c
EVLA 241 (45.8) 26 (26.8) 215 (50.1)
RFA 281 (53.4) 71 (73.2) 210 (49.0)
Sclerotherapy 4 (0.76) 0 (0) 4 (0.9)
Procedures per surgeon 2.0 (5.0) 2.0 (5.0) 2.5 (5.0) .3840d
Initial VCSS 5.38 (2.04) 6.71 (2.74) 5.07 (1.72) <.001a
VCSS change
4.11 (2.04)
3.71 (3.01)
4.20 (1.74) .1289a
Thrombotic complication 3 (0.57) 0 (0) 3 (0.7) .5418c
EVLA, Endovenous laser ablation; RFA, radiofrequency ablation; VCSS, Venous Clinical Severity Score.
Categorical variables are presented as number (%). Continuous variables are presented as mean (standard deviation) or median (interquartile range).
a
The t-test.
b
The c2 test.
c
Fisher exact test.
d
Wilcoxon rank sum.
Journal of Vascular Surgery: Venous and Lymphatic Disorders Conway et al 5
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Table III. Pretreatment, post-treatment, and treatment-related change to Venous Clinical Severity Score (VCSS)
components
Pretreatment Post-treatment Treatment-related change
VCSS component UT CT UT CT UT CT
1-month follow-up VCSS components
Pain 1.98 1.81 0.31 0.07c
1.67
1.74
Varicose veins 2.06 1.91 0.47 0.03c
1.59
1.88a
Edema 0.34 0.05 c
0.08 0.03
0.26
0.02b
Pigment 0.09 0.11 0.02 0.03
0.07
0.08
Inflammation 0.02 0.03 0.00 0.01a
0.02
0.01
Induration 0.00 0.02b 0.00 0.01 0.00
0.01a
6-month follow-up VCSS components
Pain 1.43 1.86 0.50 0.02
0.93
1.84a
Varicose veins 1.50 1.86 0.21 0.05
1.29
1.81a
Edema 0.93 0.02 b
0.21 0.00
0.71
0.02b
Pigment 0.43 0.05 a
0.14 0.00
0.29
0.05
Inflammation 0.43 0.02 0.14 0.00
0.29
0.02
Induration 0.23 0.00a 0.00 0.00
0.29 0.00a
CT, Combination therapy; UT, unimodal therapy.
Data for VCSS components of total number of ulcers, ulcer duration, ulcer size, and compression not recorded in registry.
a
P < .05.
b
P < .01.
c
P < .001.

with discordance between their CEAP C2 disease severity
and their VCSS for edema, pigmentation, and induration
(UT, n ¼ 8; CT, n ¼ 48). Because we have no reliable
means of determining which entry is correct, we analyze
these variables as entered.
At the 6-month follow-up, the individual VCSS compo-
nent scores demonstrated improvement in all symptom
categories (Table III). Patients who underwent CT experi-
enced a statistically significant improvement in pain at
6 months (
1.84 for CT vs
0.93 for UT; P ¼ .0304). In addi-
tion, the score for varicose veins was significantly
improved for those who underwent CT, with a 1.81-unit
reduction compared with 1.29 units for UT (P ¼ .0388). Pa-
tients who underwent CT demonstrated minimal resid-
ual symptoms in the pain and varicose veins categories
(pain score, 0.02 vs 0.50 for UT; varicose veins score,
0.05 vs 0.21 for UT). These findings approached but did
not reach statistical significance (pain, P ¼ .0579; varicose
veins, P ¼ .1119).
Confounders of white race and day of follow-up were
identified. Age group and initial VCSS were identified
as effect measure modifiers. Neither sex nor mode of
axial reflux treatment was identified as a confounder or
effect measure modifier. As such, white race, day of
follow-up, age group, and initial VCSS were incorporated
into a multivariate model to describe the 1-month reduc-
tion in VCSS with the use of CT vs UT. We found that
VCSS reduced significantly more with the use of CT
(1.52-point excess reduction compared with UT; standard
error, 0.49; P ¼ .0019; R2 ¼ 0.549). The 6-month follow-up
model was adjusted only for initial VCSS because of the
limited sample size. At the 6-month follow-up, the use
of CT was associated with an additional improvement
in VCSS of 2.85 units (compared with UT; standard error,
1.06; P ¼ .0094; R2 ¼ 0.65).
The change in VCSS was analyzed as a function of CT
for CEAP C classes C2 through C4. On crude analysis,
CT resulted in a larger treatment-related reduction in
VCSS at 1 month compared with UT for all groups (addi-
tional VCSS reduction of 0.48, 1.82, and 2.79 points for C2,
C3, and C4, respectively; P ¼ .13, .003, and <.001, respec-
tively). The multivariable model established for the C2
patients was extended to control for CEAP C class. In
this model, the use of CT was associated with an addi-
tional reduction in VCSS of 0.97 points (P ¼ .001). Note
that initial VCSS was found to be a confounder in this
model and not an effect measure modifier as per the
previous analysis.
DISCUSSION
This study presents the results of an analysis of the AVR-
VVM, comparing the change in VCSS of patients who
underwent a combination of endovascular axial reflux
therapy and a varicosity-treating procedure with that of
patients who underwent endovascular axial reflux ther-
apy alone. We find that all patients benefit from treat-
ment of their CEAP C2 varicose veins, with an average
reduction in VCSS of 4.11 points. However, our adjusted
model indicates that the use of CT is associated with a
significantly greater reduction in VCSS than the use of
6 Conway et al
UT alone when assessed at 1 month (1.52 points more)
and at 6 months (2.85 units more) after the procedure
for this population of patients.
Regardless of the therapy chosen, patients in this
cohort experienced a mean reduction in their symptoms
of >75% as measured by the VCSS change from before
the procedure to the 1-month follow-up. In this popula-
tion of patients, the initial VCSS was found to be a signif-
icant effect measure modifier on the use of CT on VCSS
change. The analysis of the individual VCSS component
scores identifies pain and varicose veins as the predomi-
nant symptom categories relieved by the use of CT over
UT. As such, the 1.52-unit difference in VCSS severity at
1 month is a clinically meaningful reduction for patients
with CEAP C2 disease in this population of patients.
Our analysis of 6-month follow-up data suggests that
the benefit of CT is durable, with a 2.85-unit improve-
ment in VCSS detected at the 6-month follow-up.
Admittedly, the 6-month analysis is limited by the small
sample size and consequent inability to adjust for group
differences. Nevertheless, we find it reassuring that a dif-
ference in symptom severity is consistent with the 1-
month findings and persists at the delayed follow-up.
The specific difference in the VCSS pain category at
6 months may suggest that the residual varicosities
remain painful for patients who underwent UT, but
such speculation must be considered within the design
limitations of the study.
The therapeutic outcome differences with the use of
UT and CT have been compared in previous studies,
but there lacks a consensus in published literature. El-
Sheikha et al9 randomized 50 patients to a combina-
tion of EVLA and surgery vs EVLA alone and demon-
strated a higher VCSS at 12 weeks for the EVLA alone
group. Their results indicate that there is no difference
in symptom severity at 1 year, however. Interestingly,
they described 67% of patients in the EVLA-only group
needing a second procedure vs only 4% in the CT group.
Carradice et al19 randomized 50 patients to EVLA with
or without concomitant phlebectomy and demon-
strated improvement in VCSS and Aberdeen Varicose
Vein Questionnaire score with the use of concomitant
stab phlebectomy (vs EVLA alone). The effect persisted
up to 3 months but was no longer detectable at
1 year. Similarly, Lane et al20 randomized 101 patients
to receive RFA with or without stab phlebectomy and
found that the RFA with phlebectomy group had
improvement in VCSS at 6 weeks, 6 months, and
1 year. In addition, they showed that 36% of patients
who underwent RFA alone underwent a second pro-
cedure. Our results mirror these findings and demon-
strate that a CT-related treatment benefit persists
outside of the clinical trial environment.
There exists a body of literature contrasting the benefit of
a combination approach, however. Kim et al11 published
the results of a double retrospective cohort study that
Journal of Vascular Surgery: Venous and Lymphatic Disorders
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included 132 patients in which EVLA was compared with
the combination of EVLA and open surgery. Their study,
which took advantage of a change in practice patterns
at one center, indicated that there was no difference in
treatment failure between the two groups. Welch21 per-
formed duplex ultrasound assessment of great saphenous
vein (GSV) patency 1 week after RFA, finding that 84% had
total GSV occlusion or <10 cm of patency. Interestingly,
29% of patients underwent a subsequent procedure to
directly treat varicosities. Monahan22 measured changes
in varicosity size and distribution after RFA and found
that 13% of limbs had complete varicose vein resolution
at 6 months, with 88.7% of the remaining varicosities
decreasing in size. Thirty-one percent of limbs underwent
sclerotherapy directed at persistent varices. The results of
these studies suggest that the persistence of symptoms
after ablation of the GSV may be secondary to factors other
than persistent GSV reflux.
The results of this study suggest that symptoms
improved significantly at the 1-month follow-up for all
treated patients compared with the pretreatment symp-
tom severity. Several studies have evaluated patient ex-
pectations with varicose vein treatment, and
consideration of our results in such a context is informa-
tive. In a study by Shepherd et al,23 a survey was admin-
istered to 111 patients who were undergoing treatment of
varicose veins. They reported that pain was experienced
by 75% of patients, and 20% of patients indicated that
“resolution of physical symptoms” was the most impor-
tant outcome of treatment. As such, the additional 1.52-
point VCSS reduction associated with the use of CT
may indicate a therapeutic advantage for this therapy
when it is considered from the patient’s perspective.
A similar survey-based study was performed to assess pa-
tient expectations with varicose vein treatment, with 351
patients enrolled.24 In this study, one-third of patients ex-
pected “significant improvement” with treatment, with
the remaining two-thirds expecting “moderate improve-
ment.” Although these degrees of improvement are not
quantified, they do describe the patient’s expectations
with treatment. In the VCSS scale, a 1-point reduction in
any single category lowers symptoms from severe to mod-
erate or from moderate to mild. For the population of pa-
tients included in our analysis, the use of CT enhanced
symptom reduction by >1 point compared with UT.
Endovenous saphenous vein ablation is associated with
a low complication rate overall, with thrombotic compli-
cations being the most serious. A meta-analysis that eval-
uated the incidence of DVT and EHIT in thermal ablation
of the GSV included 52 studies and >16,000 patients. The
investigators described a thrombotic complication rate
of 1.7% (95% confidence interval, 0.9%-2.7%) associated
with thermal ablation of the GSV.25 In this study, overall
rate of thrombotic complications was 0.57%, without a
statistically significant difference between UT and CT
groups.
Journal of Vascular Surgery: Venous and Lymphatic Disorders
Volume -, Number -
Our study includes a large sample size of 526 patients,
spanning >5 years of procedures at academic and pri-
vate facilities, and is adjusted for clinically relevant cova-
riates such as differences in demographics and baseline
scores. Despite these strengths, our study has several lim-
itations. It is a retrospective analysis with a limited follow-
up interval, and the durability of these interventions is
not evaluated. Some symptoms of varicose veins will un-
doubtedly require >1 month to resolve, and comparing
the treatments at this time point is not representative
of the patient’s long-term outcome. We attempt to
address this with our 6-month analysis, which is limited
by small sample size, though. In addition, it is possible
that patients without residual symptoms would choose
not to follow up at the 6-month time point because
they would have no need for further intervention. Never-
theless, we are encouraged that the 6-month analysis is a
continuation of the trend seen at 1 month, suggesting
that CT may provide a more expedient resolution of
symptoms and may indeed be durable at 6-months.
Because this is a retrospective study of registry data, it
is not possible to account for the patient’s or surgeon’s
preference for treatment, the surgeon’s skill, or the peri-
operative care quality. In addition, we cannot determine
whether there was intention for a staged approach to
treatment, and we cannot ascertain whether patients
who received UT subsequently received another proced-
ure. We further are unable to reliably determine the
number of individual procedures performed per opera-
tion and the number of subsequent procedures per-
formed. The specific nature of the symptom reduction
in this population of patients is not clearly defined.
Although the VCSS does contain scores for 10 symptom
categories, the specific symptoms experienced by indi-
vidual patients were not analyzed in this study, and the
clinical impact of any particular intervention cannot be
fully understood. Inclusion of patient-reported outcomes
would potentially capture the specific changes in symp-
toms; however, such data were not available for analysis.
Varicose vein treatments are performed both in the of-
fice and in the operating room, and the choice of treat-
ment may be dictated by the availability of anesthesia
or sedation. However, the type of anesthesia was not
available for analysis in this study. Finally, the addition
of a varicosity-treating procedure undoubtedly would
lengthen overall procedure time, which was not available
for analysis.
CONCLUSIONS
Chronic venous insufficiency is a highly prevalent condi-
tion that has a significant and deleterious impact on pa-
tients’ lives. Although many treatment options exist for
varicose veins, the selection of any particular therapeutic
technique continues to depend largely on the patient’s
and surgeon’s preference. This retrospective cohort study
compares the change in symptom severity from a
Conway et al 7
preoperative baseline to a 1-month follow-up evaluation
between patients who received CT addressing the axial
vein reflux and varicosities and patients who received
endovascular therapy alone. We find that patients
receiving CT experience a greater reduction in symp-
toms. In this study, the typical patient experiences a
reduction of symptoms by >75% regardless of the
selected therapy. These results indicate the efficacy of
both varicose vein treatment approaches and provide ev-
idence of a preferential benefit of CT for the resolution of
symptoms in this population of patients.
AUTHOR CONTRIBUTIONS
Conception and design: RC, AB, BL
Analysis and interpretation: RC, AB, BL
Data collection: JA, LK, TW, BL
Writing the article: RC, AB, BL
Critical revision of the article: RC, JA, LK, TW, AB, BL
Final approval of the article: RC, JA, LK, TW, AB, BL
Statistical analysis: RC, AB, BL
Obtained funding: BL
Overall responsibility: BL
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Submitted Jul 11, 2019; accepted Oct 13, 2019.