Long term outcome of minimally invasive treatment for superficial venous insufficiency of the lower limb

El-Sheikha, Joseph

Abstract

Background
Venous insufficiency is estimated to affect up to half of the adult population and is associated with significant quality of life (QoL) impairment. Minimally invasive techniques, such as Endovenous Laser Ablation (EVLA) aim to treat superficial venous insufficiency (SVI) by using thermal energy to destroy the incompetent venous axis. Numerous studies have reported that the EVLA method is superior to Conventional surgery, a previously standard technique, which uses ligation and stripping of the incompetent axis to remove venous reflux associated with SVI. In the short term, EVLA is associated with fewer complications and enhanced QoL recovery compared to conventional surgery, but the long term outcomes remain uncertain.

Objectives
The aim of this study was to investigate the five year outcomes of EVLA and conventional surgery in the treatment of SVI. The HELP-1 trial directly compared the clinical and technical outcomes of conventional surgery and EVLA. The EVLTAP trial compared the long term consequences of a policy of concomitant or sequential phlebectomy with EVLA. Due to advantageous size of the HELP-1 study, a comparison of the long term outcomes of patients with different severities of SVI was also explored. A cost effective analysis was also undertaken. Finally, investigation of the importance of different EVLA settings and techniques was investigated.

Methods
The HELP-1 and EVLTAP studies were both randomised clinical trials. All patients had primary, symptomatic, unilateral venous insufficiency, with isolated Sapheno-femoral junction (SFJ) incompetence, leading to reflux into the great saphenous vein (GSV). In the HELP-1 study, 280 patients were equally randomised into two groups of either conventional surgery or EVLA. In the EVLAP trial, 50 patients were equally randomised into two groups of either concomitant phlebectomy or sequential phlebectomy. Both groups were offered sequential phlebectomy of any symptomatic residual venous tributaries present after six weeks. Outcomes were generic QoL (Short form 36 (SF-36), EuroQoL 5 Dimension (EQ5D), Disease specific QoL (Aberdeen Varicose Vein Questionnaire AVVQ), Utility Index QoL (SF6D), Objective clinical assessment of venous disease (VCSS), Cosmetic and overall satisfaction, clinical recurrence, symptomatic recurrence and requirement of additional procedures. Assessments were at 1, 6, 12, 52, 104, 260 weeks.

The further study of EVLA settings and technique used linear and logistic regression modelling to investigate the effects of Watt power (12W or 14W) and concomitant phlebectomy on QoL (SF-36, EQ5D and AVVQ), clinical outcomes and recurrence. For the economic analysis, costs were calculated using prospective data estimated from the actual resource requirement in each case over five years. Health utility index from the EQ5D or SF6D was used to calculate quality adjusted life years (QALYs) over five years using Area under the Curve (AUC). The Cost per QALY increase was calculated to produce a cost effective ratio (ICER) to determine cost effectiveness at various economic limits. Sensitivity analysis explored parameter uncertainty. For EVLTAP a Monte Carlo simulation was developed to explore the additional costs of various thresholds for sequential phlebectomy.

Results
Over five years, the HELP-1 trial detected early deterioration in the SF-36 QoL domains of Physical function (PF), Role physical (RF), Bodily pain (BP), Social function (SF) and Role emotional (RE) after conventional surgery After EVLA only the domains of PF and RP were impacted. Beyond one year, improvement in the domains of PF, BP and Mental health (MH) were maintained after conventional surgery, as were the domains of PF and BP after EVLA. At five years, all SF-36 domains in both groups had returned to baseline, aside from Social Function (SF) which was worse in both groups. Beyond one year, no differences in SF-36 domains were detected between the groups at any time point. Improvement in AVVQ and EQ5D was sustained in both groups, as was objective measure of venous disease (VCSS), with no differences detected between the two treatments. Overall satisfaction and cosmesis remained high. Over five years, clinical recurrence was detected in 56.4% and 44.4% of conventional surgery and EVLA patients respectively (P=0.078). Estimated freedom from clinical recurrence was higher after EVLA (P=0.031). Over five years, symptomatic recurrence was detected in 18 and 19 conventional surgery and EVLA patients respectively (P=0.862) and likelihood of symptomatic recurrence development was similar between both groups (P=0.983). The proportion of those requiring additional procedures were similar between both groups over five years (P=1.000).

Over five years, the EVLTAP trial detected an early improvement in AVVQ at six weeks among those receiving concomitant phlebectomy (P=0.008). At 12 weeks both groups reported an improvement in AVVQ (EVLA alone P=0.018, EVLTAP P<0.001). Compared to sequential phlebectomy, concomitant phlebectomy had lower (better) AVVQ scores at 6 weeks (P=0.008) and 12 weeks (P=0.015). Beyond one year both groups reported significantly improved with no intergroup differences detected. Sequential phlebectomy was required in 66.7% of those in the EVLA alone group, and 4% of those in the EVLTAP group. The requirement for additional intervention after one year was however similar between the two groups.

From the HELP-1 trial data, more severe baseline disease (CEAP 3-4) was associated with worse long term outcomes compared to those with uncomplicated venous disease (C2). Clinical recurrence arose in 70% of those with C3-4 disease and 43% of those with C2 disease. Symptomatic recurrence was also higher in those with complicated disease, at 27% and 12% in C3-4 and C2 groups respectively. Whereas QoL improvement was maintained to five years in the domains of RP, RP, Vit and RE among those with C2 disease, those with C3-4 disease did not manage to sustain any improvement in any SF-36 QoL domain. However, over five years both groups did improve in disease specific measures of VCSS and AVVQ. Additional treatments were also more prevalent amongst those with C3-4 disease.

Economic analysis suggested that the initial treatment costs of EVLA were less than conventional surgery, but after one year costs were broadly the same. QALYs were also similar between both treatments. Cost effectiveness over five years was similar between both treatments, with marginal improvement of QALY but more cost among conventional surgery. Significant costs associated with the long term treatment of those with C3-4 disease and worse QoL outcomes suggested that treatment of C2 disease was much more cost effective overall. Performing EVLA without concomitant phlebectomy is both quicker and cheaper, but additional costs of sequential phlebectomy by one year inflate the overall costs to beyond that of the concomitant group. Costs beyond one year are similar. Monte Carlo modelling suggests that sequential phlebectomy is highly unlikely to be more cost effective at any threshold of further intervention.

Investigation into the effects of EVLA setting and technique found that at 12 weeks, PF, Vit and MH were enhanced in those receiving the 14W continuously delivered EVLA versus those receiving the 12W pulse delivered EVLA. Early benefit in PF and AVVQ was also detected in those receiving concomitant phlebectomy. Beyond 12 weeks there was no significant difference in QoL detected, nor did the treatment ultimately effect the clinical outcomes or recurrence.

Conclusion
EVLA and conventional surgery are both highly effective long term treatments for SVI. In considering the early benefits, this study supports the recent NICE guidance that EVLA should be preferred over conventional surgery. Concomitant phlebectomy during EVLA appears to be the optimum treatment, and treating those with SVI earlier, appears to produce better long term outcomes.

Citation

El-Sheikha, J. (2015). Long term outcome of minimally invasive treatment for superficial venous insufficiency of the lower limb. (Thesis). Hull York Medical School, the University of Hull and the University of York. Retrieved from https://hull-repository.worktribe.com/output/4219553

• Thesis Type: Thesis
• Deposit Date: Aug 29, 2017
• Publicly Available Date: Feb 23, 2023
• Keywords: Medicine
• Public URL: https://hull-repository.worktribe.com/output/4219553
• Additional Information: Hull York Medical School, The University of Hull and University of York
• Award Date: Dec 1, 2015