Varisolve^® polidocanol microfoam compared with surgery or sclerotherapy in the management of varicose veins in the presence of trunk vein incompetence: european randomized controlled trial

surgery or sclerotherapy in the management ofvaricose veins in the presence of trunk veinincompetence: European randomized controlled trial D Wright*, J P Gobin-, A W Bradbury , P Coleridge-Smith§, H Spoelstra**,D Berridge--, C H A Wittens , A Sommer§§, O Nelzen*** and D Chanter---,on behalf of the Varisolve *Provensis Limited, London, UK; -Cabinet De Medecine Vasculaire, Lyon, France; ++University of Birmingham, andHeart of England NHS Foundation Trust, Birmingham, UK; §UCL Medical School, The Middlesex Hospital, London,UK; **Therapeutisch Vascular Centrum, Gavere, Belgium; --Leeds Vascular Institute, The General Infirmary at Leeds,Leeds, UK; Department of Vascular Surgery, Sint Franciscus Gasthuis Kleiweg, Rotterdam, The Netherlands; §§Department of Dermatology, University Hospital Maastricht, Maastricht, The Netherlands; ***Vascular SurgeryUnit, Department of Surgery, Skaraborg Hospital, Skovde, Sweden; ---Statisfaction Statistical Consultancy Ltd,Bexhill on Sea, UK AbstractObjective: To compare the safety and efficacy of Varisolves 1% polidocanol microfoamsclerosant with alternative treatments for patients with varicose veins and trunk veinincompetence.
Methods: An open-label, multicentre, prospective trial of 710 patients randomized to receiveeither Varisolves or alternative treatment (surgery or sclerotherapy). The endpoint wasultrasound-determined occlusion of trunk vein(s) and elimination of reflux, analysedagainst a non-inferiority hypothesis.
Results: Overall, non-inferiority was demonstrated with 83.4% efficacy for Varisolvescompared with 88.1% for alternative treatment at three months, and the correspondingmagnitudes were 78.9 and 80.4% at 12 months. Surgery was superior to Varisolves, but thesuccess rate of 68.2% for Varisolves (surgery 87.2%) was poor compared with 93.8% successfor Varisolves achieved in those randomized to Varisolves or sclerotherapy. Varisolveswas superior to sclerotherapy at 12 months (P ¼ 0.001). Deep vein thrombosis occurred in11/437 (2.5%) after Varisolves, in 1/125 (0.8%) after sclerotherapy and in none after surgery.
No pulmonary emboli were detected.
Conclusion: Overall, Varisolves was non-inferior to alternative treatment. Surgery wasmore efficacious, but Varisolves caused less pain and patients returned to normal morequickly. The Varisolves technique is a useful additional treatment for varicose veins andtrunk vein incompetence.
Keywords: Polidocanol microfoam; varicose veins; trunk vein incompetence; venousdisease management Correspondence: Mr David Wright FRCS, ProvensisLimited, BTG Plc, 10 Fleet Place, Limeburner Lane, LondonEC4M 7SB, UK.
Email: [email protected] Varicose veins are a common problem, present in approximately 25% of the western adult popula- Patients aged 18–75 years with varicose veins and tion.1 Early varicose veins are relatively benign, but great and/or small saphenous vein incompetence some patients will progress to develop severe and were recruited from the clinical practice of inves- irreversible problems of chronic venous insuffi- tigating physicians. Eligible patients were assessed and assigned to receive either surgery or scler- Surgery, by high ligation and stripping of trunk otherapy based on the extent of their disease and veins, is still considered the ‘gold standard’ for physician preference. Once the alternative treat- treatment of varicose veins in association with ment had been selected, they were randomized to trunk vein incompetence. Surgery has been demon- either the Varisolves technique or the chosen strated to be more efficacious and durable than alternative treatment. Thus, two separate cohorts sclerotherapy, but its position as the standard of were created: Varisolves/surgery and Varisolves/ care has been challenged more recently by heat sclerotherapy. The key inclusion and exclusion ablation therapy (radio frequency ablation [RFA] or criteria for the study are shown in Box 1.
endovenous laser therapy [EVLT]).4,5 Recurrence Regulatory and local ethics committee approval following surgery remains a problem, and the was obtained for each centre, and all patients gave occurrence of surgical complications, although infrequent, highlights the need for an effective,safe and patient-friendly treatment.6,7 Heat abla-tion treatments have met this need in part, but are linked with pain and bruising, skin burns, para-esthesias, phlebitis, deep vein thrombosis (DVT) This was an open-label, international, multicentre, and pulmonary embolism (PE).8–13 Sclerotherapy randomized Phase III study to evaluate the safety using liquid sclerosant is effective for the treatment and efficacy of the Varisolves technique using of telangiectasias and small varicose veins. How- polidocanol 1% microfoam in comparison with ever, controlling the dose and its distribution is alternative treatments in the management of patients with moderate-to-severe varicose veins.
There is no consensus about which treatment is The investigators were selected on the basis of their most effective for varicose veins. A recent review expertise in venous disease management and comparing surgery and sclerotherapy concluded ability to recruit adequate patient numbers. These that there was insufficient evidence to recommend were either experienced vascular surgeons, some either treatment preferentially.15 However, the with limited experience of sclerotherapy prior to application of ultrasound guidance to sclerother- the study, or experienced phlebologists (primarily apy has led to improvements in this technique.16,17 from France). Investigators were provided with the The invention of sclerosant microfoam that Varisolves Training Manual and the accompany- displaces blood from the vessel has resulted in ing video, and were supervised during the first five successful treatment of larger veins, including the treatments or until basic proficiency was demon- great saphenous vein (GSV).14,18 In comparative studies, polidocanol microfoam was more effica- Screening assessments included physical exam- cious than liquid in the treatment of saphenous ination, medical history, haematology and bio- veins.19–21 It is also effective in the treatment of chemistry laboratory tests. Clinical examination some vascular malformations and chronic venous and duplex scanning of the leg determined the insufficiency causing leg ulcers.14,18,21 patients’ CEAP classification22 and allowed the Varisolves polidocanol microfoam was devel- investigator to select a suitable treatment for each oped to provide several advantages over investi- Patients underwent central randomization to microfoam quality, bubble size and sterility.
either the Varisolves technique or alternative The aim of this study was to compare the safety treatment at a ratio of 2:1 in favour of the and efficacy of the defined technique using Varisolves technique (Figure 1). The surgical or polidocanol 1% microfoam formulation against sclerotherapy approach used as an alternative to that of alternative treatments (surgery or scler- Varisolves was not specified. Any marketed otherapy) for varicose veins and trunk vein sclerosant at any marketed concentrations was permitted either as liquid or investigator-generated Box 1 Key inclusion and exclusion criteria  History of major superficial thrombophlebitis  Venographic or ultrasonographic evidence of current or previous  SFJ or SPJ junction incompetence or both with retrograde blood flow for 41 s and o7 s demonstrated by duplex scanning  Immobility – unable to walk a minimum of 5 min/h/day  Great saphenous incompetence and/or short saphenous  Contraindications for polidocanol: severe hypertension,  Minimum of 10 cm proximal trunk vein incompetence glomerulonephritis and nephroses, hepatopathy, active phlebitis,  Normal arterial circulation; ankle: brachial pressure ratio 40.9 general febrile disease, diabetes, asthma, advanced  Haematology and blood chemistry profiles within normal/ acceptable limits, i.e. abnormalities not clinically significant  Serious coexisting illness including carcinoma, cardiac or  Normal deep venous system on duplex scanning, no evidence of respiratory disease, past or present venous ulcers; pregnancy or occlusion or incompetence. Evidence of reflux was acceptable, however, if it was confined to a limited segment caused by filling of  Concomitant treatment with disulfiram, systemic corticosteroids,  Known allergic response to polidocanol or severe allergic diathesis Abnormal, clinically significant haematology or biochemistry foam. Efficacy and safety was assessed by duplex scanning on days 7 and 28, and at months 3 and 12.
confirmed by ultrasound before further injec- If additional treatment was necessary, this was tion of the distal trunk vein through the same performed on days 7 and 14 for patients treated cannulation site with digital compression of with Varisolves, and between days 7 and 21 for the GSV or SSV proximal to the cannula tip.
Any residual varicosities were injected withVarisolves using a butterfly needle.
Once treatment was complete, compression,consisting of an under bandage from ankle to Varisolves polidocanol microfoam is a uniform groin, foam pads along the treated veins, a foam of physiologic gases, principally oxygen (O2) second layer of bandage, a thin overstocking, and carbon dioxide (CO2), combined with a 1% and finally 30–40 mmHg thigh-length com- aqueous solution of polidocanol. It is generated at pression stocking (Sigvaris) was applied.
the point of use from an aerosol canister. The maximum total dose of microfoam was initially set treatment: day and night for the first seven at 60 mL, and this was subsequently reduced to days. Patients were advised to walk for 5 min 30 mL. The aims of the Varisolves technique are to in each waking hour for the first seven days eliminate all deep to superficial vein reflux and occlude associated trunk veins and superficialvaricosities.
The Varisolves technique was carried out under ultrasound guidance in five stages in accordancewith the Training Manual.
During the study, modifications to the treatmentprocedure were implemented, intending to reduce (1) Ultrasound-guided cannulation of the trunk vein and proof of venous access to avoid intra- treatment session to 30 mL and required the (2) Injection of microfoam into the trunk vein, injection to be stopped and compression applied filling the vein from the cannulation site to its to the terminal GSV or small saphenous vein termination with the deep vein, while care- (SSV) when microfoam was seen 5 cm from the fully monitoring either the saphenofemoral SFJ or SPJ. In addition, the maximum volume (SFJ) or saphenopopliteal junctions (SPJ) for of the initial injection of the trunk vein was the arrival of microfoam. After foam was seen calculated based on the distance (in cm) from at the junction, the trunk vein was compressed the point of cannulation to the junction. Retrograde to stop microfoam from freely passing into the filling of the small saphenous vein trunk was Figure 1 Patient disposition. M3, Month 3; M12, Month 12. aStudy interrupted by sponsor; bAdverse event; cPatient decision; dOther reasons; eMissing; fFirst treatment (Leg 1) mined by compression and colour flow fillingduring and following calf compression. The status Duplex scans were carried out by experienced of each vein was scored at screening and at each technologists or physicians. They were trained to follow a detailed protocol that required theimaging of all major veins. The deep calf veins were repeatedly checked throughout their lengthfor the presence of thrombus by repeated probe The primary endpoint was the response to treat- compression, and their competence was deter- ment at Month 3, defined as the occlusion of incompetent trunk vein(s) from the source of deep with sclerotherapy in the Varisolves/sclerotherapy to superficial flow and the elimination of reflux cohort. Of the treated patients, all but two patients greater than 0.5 s in the treated vein(s) 2–5 cm from who provided no post-treatment data (both treated its point of termination, as determined by duplex with Varisolves in the Varisolves/surgery cohort) scanning. In order to be considered a responder, were included in the statistical analysis.
both occlusion (or for surgery, absence) of the Patient demographics were typical of varicose treated vein and elimination of junctional reflux vein treatment populations (Table 1), with the were required. If the GSV and SSV had been majority being women, mean age 50 years, and treated, both veins had to meet both criteria in few patients with recurrent disease following order for the patient to be classified as a responder.
The secondary endpoints included: severity of The two cohorts were similar in most respects.
post-procedure pain (days 1–6 measured using a However, the Varisolves/sclerotherapy cohort had visual analogue scale [VAS]), time taken to return more female patients (71.9 versus 63.2%; P ¼ 0.022, to normal activities, number of treatment sessions Fisher’s exact test), more recurrent varicosities (16.9 required and Month 12 response rate.
versus 8.9%; P ¼ 0.003, Fisher’s exact test), asmaller 7.9 mm; Po0.001, Student’s t-test) and a higher proportion of patients with SSV disease (23.4 The statistical analysis was based on comparison of versus 13.0%; Po0.001, Fisher’s exact test), than response rates following Varisolves or alternative therapy using meta-analysis to combine the The CEAP classification was recorded at entry Varisolves results and the alternative therapy and was dominated by C2, Ep, As, Pr patients. All results from the two cohorts to test a non-inferiority patients had to have varicose veins (C2) to be hypothesis. The intended sample size of 650 included, and oedema or skin changes (C3/C4) patients was chosen to demonstrate non-inferiority were permitted. Patients with healed and open of Varisolves, assuming an 85% response rate with ulcers (C5, C6) and evidence of post-thrombotic deep-vein disease were excluded. Aetiology was Non-inferiority was to be deemed established if primary in 98.2%, and all patients had incompetent the lower bound of the 95% confidence interval (CI) superficial veins. Incompetent perforator veins for the treatment difference (Varisolves– alterna- were present in only 12.1% of patients, and deep tive treatment) did not lie below À15 percentage vein incompetence was present in only 2.5% of points. The two independently randomized cohorts patients (only permitted if isolated and draining (Varisolves/surgery and Varisolves/sclerother- into superficial veins), all but three of 19 incompe- apy) were analysed separately. The proportions of tent deep vein segments became competent after patients responding at Month 3 were compared treatment. There were differences in the propor- between the treatment groups using a logistic tions of patients classified as C3 and C4 between regression analysis, with covariate adjustment for the two groups of Varisolves-treated patients: a number of prespecified factors, including gender, significantly more patients in the Varisolves/ disease status and study centre. Missing data were sclerotherapy cohort were C3, (22 versus 7.9% in imputed using the last observation carried forward the Varisolves/surgery group; Po0.001), conver- technique, provided that data were available for at sely more patients had C4 recorded in the Varisolves/surgery cohort’s, but this differencewas not statistically significant (11.2 versus 6.9%;P ¼ 0.075) (Fisher’s exact test).
Of the total patients, 710 were randomized, ofwhich 54 were withdrawn before treatment as it was delayed to permit a review of potential causes High ligation was performed in 91.5% of patients of DVT; 656 patients were treated and 26 patients randomized to this approach, stripping in 88.3%, withdrew from the study after treatment (Figure 1).
and avulsion phlebectomy in 53.2% of patients.
In the Varisolves/Surgery cohort, 178 patients General anaesthesia was used in 57.4% and local were treated with Varisolves and 94, with surgery, anaesthesia (including regional) in 42.6% of surgi- while 259 were treated with Varisolves and 125 cal procedures; median operating time was 49 min Table 1 Patients’ baseline demographic data SD, standard deviation; GSV, great saphenous vein; SSV, short saphenous vein; *All patients were C2 and above: C5 and C6 were exclusion criteria; -C3 more frequent in Varisolves/sclerotherapy cohort, Po0.001; C4 more frequent Varisolves/surgery cohort, Po0.075 not (range: 15–200 min). Prophylactic perioperative Varisolves technique to surgery was not demon- anticoagulation was used in 22% of patients.
strated, while conversely there was a small butnon-significant trend (P ¼ 0.06) in favour of theVarisolves technique relative to sclerotherapy in the Varisolves/sclerotherapy cohort.
Polidocanol and sodium tetradecyl sulphate were At Month 12, overall non-inferiority was again used with approximately equal frequency (61 and demonstrated: efficacy was 78.9% for Varisolves 64 patients, respectively). Investigators used their and 80.4% for alternative therapies (lower limit of own homemade foam rather than liquid in 92% of 95% CI for difference: –10%). The superiority of treatments. Sclerosants were used in concentrations surgery over Varisolves was maintained (86.2 ranging from 0.5 to 3%; the mean volume was versus 63.1%). In the Varisolves/sclerotherapy 9.8 mL for foam and 3.5 mL for liquid.
group, when comparing Month 3 and Month 12response rates, there was greater loss of efficacy with sclerotherapy than with Varisolves (12.8% forsclerotherapy versus 4.2% for Varisolves), such Response rates at Months 3 and 12 are shown in that the Varisolves response rate at Month 12 Table 2. The overall response rate was 83.4% for (89.6%) was statistically superior to the response Varisolves and 88.1% for alternative therapy at rate for sclerotherapy (76.0%; Po0.001).
Month 3, and 78.9% and 80.4%, respectively, atMonth 12. At Month 3, the lower limit of the 95% CI for the difference in response rate betweenVarisolves and alternative treatment was –13%.
Surgery was associated with more pain than the This confirmed the non-inferiority of the Vari- Varisolves treatment and this difference extended solves technique relative to the combined alter- throughout the first week (day 6: surgery median VAS score 9, Varisolves VAS score 2, full scale Analysing the cohorts separately at Month 3, the 0–100; Po0.001, Mann–Whitney test).
response rates were 68.2% for Varisolves and In the Varisolves/surgery cohort, the median time to resumption of normal activities following 93.8% for Varisolves and 88.8% for sclerotherapy treatment was considerably shorter in the Var- (Varisolves/sclerotherapy). Non-inferiority of the isolves group (2 days) than in the surgery group Table 2 Response rates* at Month 3 and Month 12 Response defined as occlusion of trunk vein and elimination of reflux at Months 3 and 12Month 3Varisolves/surgery cohort Response defined as elimination of reflux at Months 3 and 12Month 3Varisolves/surgery cohort CI, confidence interval; *Overall adjusted results are based on a meta-analysis of the combined individual cohort results; -Adjusted difference, back transformed from the odds ratio obtained from logistic analysis (13 days; Po0.001, Mann–Whitney test). No within 24 h of treatment, including paraesthesias, difference was observed between the treatment visual and speech disorders. These were short lived groups in the Varisolves/sclerotherapy cohort and there were no clinical findings during follow- for time to resumption of normal activities (1 day More patients completed treatment in one treat- ment session in the Varisolves group than in thesclerotherapy group (92.2 versus 74.4%, respec- By protocol, all DVT, including asymptomatic tively) (Table 3). When vascular surgeons per- cases, were classified as serious adverse events formed the Varisolves technique, only 82.0% (SAEs). DVT was the most frequent SAE, occurring completed the treatment in a single session, 16.9% in 11 Varisolves-treated patients (9 [4.5%] in the required two sessions and 1.2% three sessions.
Varisolves/surgery cohort and 2 [0.8%] in the Vascular surgeons used a mean of 24.9 mL (range Varisolves/sclerotherapy cohort) and in one scler- 5.0–55.0 mL) of Varisolves microfoam during the otherapy patient (0.8%). Of these, all but two were initial treatment in the Varisolves/surgery cohort detected at Day 7 post-treatment safety duplex compared with 14.9 mL of Varisolves (range: scan. Four DVT were symptomatic, but only two 2.0–60.0 mL) (Po0.001, Student’s t-test) for patients involved symptoms directly attributable to DVT.
treated by phlebologists in the Varisolves/scler- Two patients were hospitalized for intravenous anticoagulant therapy. One patient developedDVT nine months after treatment, which was considered unrelated to treatment and caused byBaker’s cyst (Table 5). There were no clinically The most common adverse events related to the use apparent cases of PE and no diagnostic tests for PE of Varisolves were mild contusion, skin disco- were required. Most cases of DVT were treated louration and limb pain; there were no cardiac or with anticoagulants, all but one resolved without pulmonary adverse events suggestive of gas sequelae. The incidence of DVT prompted techni- embolism related to the administration of micro- que changes (see Methods) and following their foam (Table 4). There were six reports of non- implementation, no further DVT were reported in specific transient neurological symptoms occurring the 95 patients treated subsequently.
Table 3 Number of sessions required to complete the course of treatment at Month 3 *Only patients who completed the study are included Table 4 The five most common treatment-related* adverse events *Related was defined as related, possibly related, or probably related to study treatment There were no other SAEs related to Varisolves highlighting the rigorous efficacy endpoint em- treatment. There were two treatment-related SAEs reported in patients treated with surgery, both Varisolves proved to be inferior to surgery when associated with anaesthesia (one episode of nausea delivered by vascular surgeons (68% Varisolves, requiring hospital admission and one failure of regional anaesthesia), which resolved without Where treatment was delivered by phlebologists sequelae. There were no clinically significant (mostly in France), a remarkable 93.8% response changes in clinical chemistry, haematology or rate was achieved at Month 3. Possible explana- tions for the reduced efficacy when Varisolves wasdelivered by the vascular surgeons include the factthat most vascular surgeons had limited experience of sclerotherapy for large veins and that theytended to use ultrasound technologists to carry This randomized, multicentre study is the first to out and report the duplex scans. To deliver the compare the Varisolves technique with alternative Varisolves technique, surgeons either had to learn treatments for varicose veins and is one of the to coordinate the ultrasound probe and their hand largest and most rigorous studies performed to movements or needed to develop an interdepen- date in this condition. In other studies, either dent working practice with the ultrasound technol- occlusion of the vein, or more commonly, elimina- ogist. However, phlebologists use ultrasound- tion of reflux, has been used to determine the guided sclerotherapy as their routine management efficacy of the treatment.15 In this study, patients of varicose veins of truncal origin. Some of the were required to demonstrate both elimination of differences might also be accounted for by less reflux and occlusion of the treated vein in order to severe disease in the Varisolves/sclerotherapy be considered a responder. Furthermore, if both the cohort in which vein diameters were smaller and GSV and SSV were treated, only patients with fewer C4 patients were recorded, although this was elimination of reflux and occlusion in both of the offset by the higher frequency of recurrent vein treated trunk veins were classified as responders, disease and C3 patients reported in this group. The differences in skill base and outcome between the cohorts suggest that additional training and experience may improve Varisolves technique outcomes, even though analyses did not demon- strate a training effect or learning curve.
isolves/sclerotherapy cohort, the response rate with Varisolves fell by 4%, whereas with scler- otherapy the response fell by 12%; those who underwent surgery had the smallest reduction in response (1%). Further studies will be required to determine the durability of microfoam sclerother-apy treatment beyond one year; however, as most believe varicose disease to be progressive and retreatment is straightforward, the importance of long-term efficacy is diminished. It is also antici- pated that once the Varisolves technique is fullyevolved and executed by experienced practitioners, whether surgeon, phlebologist, or interventional radiologist, the response rate will be similar to that (around 90%) and, therefore, equivalent to the It is surprising to find that at Month 3, 15% of patients treated surgically still had residual venous reflux in the saphenous trunk. However, this emphasizes that surgical treatment is imperfect The Varisolves technique was generally well tolerated; local adverse events, such as contusion, skin discoloration and limb pain, were generally mild in intensity and resolved without sequelae.
The only SAE associated with the Varisolves treatment was DVT. Here again there was a striking difference between Varisolves delivered by vascu- lar surgeons and phlebologists; an incidence rate of 4.5% compared with 0.8%, respectively, the latter being equal to the rate with sclerotherapy. No patients treated surgically developed DVT, which may reflect the use of pharmacologic DVT prophy- laxis in 22% of patients in conjunction with non-pharmacological prophylaxis. The high rate reported for DVT also reflects the detailed and systematic duplex scanning required by the study protocol, which may have revealed the true rate of thrombotic events, but not their clinical signifi- cance. No cases of PE were clinically apparent and most of the DVT were detected by routine duplex DVT is a recognized complication of all varicose vein treatments, including surgery, sclerotherapy, RFA and EVLT.23–25 The incidence of DVT follow- ing varicose vein surgery has generally been reported as low, but two recent studies with routine prospective duplex scanning reported incidences of 4 and 5.3%,26–28 comparable with this study. PE has been reported as rare following vein surgery, but insystematic reviews of over 4000 and 1000 patients, We gratefully acknowledge the other members of the incidence of clinically suspect PE was found to the Varisolves investigator group who participated in this trial: Jean-Patrick Benigni, Roeland Ceulen, There were no DVTs after changes were made to Alun Davies, Gilles Gachet, Pierre Ouvry, Patrick the Varisolves technique used in the study. It is Patural, Paolo Ruscelli, Peter Rutter, Symon thus reasonable to conclude that DVT may be Sadoun, Uli Taucher, Stephen Tristram and Joep minimized by administration of Varisolves by Veraart. We also thank Janet Rush for her assistance experienced practitioners using smaller volumes and careful review, and Sigvaris Ltd for the of microfoam and stopping the microfoam 5 cm distal to the termination of the trunk vein. It isadvisable to continue using the follow-up scan after one week, so that any minor thromboticevents can be treated before they become clinically 1 Callam MJ. Epidemiology of varicose veins. Br J Surg evident, thus avoiding serious sequelae.
Foam sclerotherapy deliberately introduces gas 2 Evans CJ, Fowkes FG, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic venous insufficiency in men into the venous system previously considered and women in the general population: Edinburgh Vein dangerous unless in very small quantities, compli- Study. J Epidemiol Commun Health 1999;53:149–53 cations that could be attributed to pulmonary gas 3 Callam MJ, Harper DR, Dale JJ, Ruckley CV. Chronic embolism were absent in both Varisolves and ulcer of the leg: clinical history. BMJ (Clin Res Ed) sclerotherapy-treated patients (92% air foam).
4 Lurie F, Creton D, Eklo¨f B, et al. Prospective randomized Minor neurological and ocular events including study of endovenous radiofrequency obliteration (clo- migraine that could be attributed to cerebral gas sure procedure) versus ligation and stripping in a embolism, following the presumed passage of selected patient population (EVOLVeS Study). J Vasc bubbles across a right to left circulatory shunt, were infrequent and transient. Similar findings 5 Min RJ, Khilnani N, Zimmet SE. Endovenous laser treatment of saphenous vein reflux: long-term results.
have been reported by others including Guex et al.32 The passage of gas bubbles through the 6 Neglen P, Einarsson E, Eklo¨f B. The functional long-term microvasculature has been studied experimentally value of different types of treatment for saphenous by Eckmann et al.,33 the results of which suggest vein incompetence. J Cardiovasc Surg (Torino) 1993;34: that the method of foam manufacture and gas 7 Fischer R, Chandler JG, De Maeseneer MG, et al.
composition have a highly significant influence The unresolved problem of recurrent saphenofemoral over the potential for gas bubbles to occlude the microvasculature and, by inference, cause cerebral 8 Rautio T, Ohinmaa A, Perala J, et al. Endovenous symptoms. In this study, there were few neurolo- obliteration versus conventional stripping operation in gical or visual events reported and no difference in the treatment of primary varicose veins: a randomizedcontrolled trial with comparison of the costs. J Vasc Surg frequency between physician-generated air-based foam and Varisolves, predominantly made with 9 Dauplaise TL, Weiss RA. Duplex guided endovascular occlusion of refluxing saphenous vein. J Vasc Technol In conclusion, the Varisolves technique is cap- able of sclerosing major incompetent trunk veins 10 Weiss RA, Weiss MA. Controlled radiofrequency endovenous occlusion using a unique radiofrequency and tributaries in a single outpatient session. This catheter under duplex guidance to eliminate saphenous study showed the Varisolves technique to be varicose vein reflux: a 2-year follow-up. Dermatol Surg effective in over 80% of patients and to be a well- tolerated treatment for varicose veins and trunk 11 Goldman MP, Amiry S. Closure of the greater saphe- vein incompetence. In experienced hands, the nous vein with endoluminal radiofrequency thermalheating of the vein wall in combination with ambulatory Varisolves technique caused only mild discomfort, phlebectomy: 50 patients with more than 6-month permitting rapid return to normal activities. Long- term efficacy is yet to be established, and the 12 Merchant RF, DePalma RG, Kabnick LS. Endovascular relative merits in comparison with RFA and EVLT obliteration of saphenous reflux: a multicenter study.
need to be studied. These benefits make the 13 Proebstle TM, Gul D, Kargl A, Knop J. Endovenous Varisolves technique an appropriate future treat- laser treatment of the lesser saphenous vein with a 940- ment for patients with varicose veins and trunk nm diode laser: early results. Dermatol Surg 2003;29: 14 Cabrera J, Cabrera Jr J, Garcia-Olmedo MA, Redondo P.
24 Manfrini S, Gasbarro V, Danielsson G, et al. Endovenous Treatment of venous malformations with sclerosant in management of saphenous vein reflux. Endovenous microfoam form. Arch Dermatol 2003;139:1409–16 Reflux Management Study Group. J Vasc Surg 2000;32: 15 Rigby KA, Palfreyman SJ, Beverley C, Michaels JA.
Surgery versus sclerotherapy for the treatment of 25 USA Food and Drug Administration. Manufacturer and varicose veins. Cochrane Database Syst Rev 2004, Issue User Facility Device Experience Database (MAUDE) Avail- 16 Knight RM, Vin F, Zygmunt JA. Ultrasonic guidance of 26 Bhogal R, Hickey NC, Nyamekye IK. Selective venous injections into the superficial venous system In: Davy A, duplex imaging detects all clinically relevant DVT after Stemmer R (eds). Phle´bologie 89. Paris, France: John varicose veins surgery [Abstract]. Phlebology 2005; 17 Schadeck M, Allaert F. Ultrasonography during scler- 27 Critchley G, Handa A, Maw A, Harvey A, Harvey MR, otherapy. Phlebologie 1991;44:111–30 [Article in French] Corbett CR. Complications of varicose vein surgery.
18 Cabrera J, Cabrera Jr J, Garcia-Olmedo MA. Sclerosants in microfoam. A new approach in angiology. Int Angiol 28 Puttaswamy V, Fisher C, Neale M, Appleberg M.
Venous thromboembolism following varicose vein 19 Hamel-Desnos C, Desnos P, Wollmann JC, Ouvry P, surgery: a prospective analysis Abstract presented at Mako S, Allaert FA. Evaluation of the efficacy of the Australian and New Zealand Society of Phlebology polidocanol in the form of foam compared with liquid form in sclerotherapy of the greater saphenous vein: 29 van Rij AM, Chai J, Hill GB, Christie RA. Incidence of initial results. Dermatol Surg 2003;29:1170–5 deep vein thrombosis after varicose vein surgery. Br J 20 Yamaki T, Nozaki M, Iwasaka S. Comparative study of duplex-guided foam sclerotherapy and duplex-guided 30 Lofgren EP, Coates HLC, O’Brien PC. Clinically suspect liquid sclerotherapy for the treatment of superficial pulmonary embolism after vein stripping. Mayo Clinic venous insufficiency. Dermatol Surg 2004;30:718–22 21 Cabrera J, Redondo P, Becerra A, et al. Ultrasound- 31 Huber O, Bounameaux H, Borst F, Rohner A. Post- guided injection of polidocanol microfoam in the operative pulmonary embolism after hospital dis- management of venous leg ulcers. Arch Dermatol charge. An underestimated risk. Arch Surg 1992;127: 22 Eklo¨f B, Rutherford RB, Bergan JJ, , et al., for the 32 Guex J-J, Allaert F-A, Gillet J-L, Chleir F. Immediate and American Venous Forum International Ad Hoc Com- midterm complications of sclerotherapy: a report of a mittee for Revision of the CEAP Classification. Revision prospective multicenter registry of 12,173 sclerotherapy of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg 2004;40:1248–52 33 Eckmann DM, Kobayashi S, Li M. Microvascular 23 Guex JJ. Thrombotic complications of varicose veins. A literature review of the role of superficial venous thrombosis. Dermatol Surg 1996;22:378–82

Source: http://sbacv.com.br/forum/XX-forum/Varisolve-Phase%20III.pdf