Long-term follow-up of endovenous treatments for varicose veins: a review of the literature

By Manj GOHEL, London, UK

Following a century of open surgical procedures, the treatment of superficial venous reflux in truncal veins has been revolutionized in recent years by the introduction and widespread acceptance of endovenous modalities. The available evidence suggests that endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) are comparable and possibly superior to traditional surgery in the short and medium terms ^{1, 2}, as regards patient-reported, anatomical, and clinical outcomes. Ultrasound-guided foam sclerotherapy (UGFS) is extremely well tolerated and versatile, although most studies have suggested lower occlusion rates than with other treatments ³. Randomized trials evaluating long-term outcomes after saphenofemoral disconnection and great saphenous vein (GSV) stripping have demonstrated varicose vein recurrence rates as high as 62% at 11 years ⁴. However, long-term outcomes following endovenous interventions (defined as ≥5 years for the purposes of this article) are poorly understood.

In a systematic review of the evidence for UGFS ⁵, 69 studies were included, of which only 10 were randomized trials. The evidence clearly suggests that foam sclerotherapy is more effective than liquid sclerotherapy. However, follow-up periods were generally less than 3 years and no randomized studies evaluating UGFS reported outcomes beyond 2 years. One study reported 10-year outcomes after liquid sclerotherapy (using polidocanol), surgery, and surgery plus sclerotherapy. Ninety-six patients completed follow-up to 10 years and the group treated with liquid sclerotherapy alone had the worst outcomes with incompetence of the saphenofemoral junction seen in nearly 20% of patients ⁶.

Although a number of randomized studies have been conducted to evaluate the endovenous thermal modalities (EVLA or RFA), none have reported outcomes beyond 2 years. In one of the earliest studies comparing EVLA and surgery (performed under local and tumescent anesthesia), Rasmussen and colleagues did not demonstrate any significant differences up to 2 years. However, recurrent varicosities were present in 26% and 37% in EVLA and surgery groups, respectively ². A review of randomized studies of RFA demonstrates a similar picture, with only 1 underpowered randomized study (15 patients in each arm) reporting outcomes beyond 2 years. However, larger prospective observational studies with longer follow-up have been published. In a prospective registry study, Merchant et al reported outcomes up to 5 years for 1222 limbs (1006 patients) treated with RFA using the original VNUS Closure™ procedure. Thirty-four centers were involved and 69.6% of patients underwent treatment for C2 disease. The study clearly demonstrated a gradual decline in anatomical success over time, with vein occlusion rates dropping from 96.8% initially to 87.2% at 5 years ⁷. A similar study from Italy reported 3-year outcomes in 1076 limbs (1050 patients) treated with EVLA over a 4-year period. In contrast to the Merchant study, occlusion rates were maintained at 97% up to 3 years ⁸.

A meta-analysis of all endovenous modalities was published in 2009 ³. The authors recognized the enormous heterogeneity in published studies and included randomized trials, and prospective and retrospective publications. In view of the variations in follow-up periods reported, the authors performed a meta-regression and presented success rates at different time points up to 5 years. Their analyses suggested that 5-year success rates were greatest after EVLA (95.4%) and lowest after UGFS (73.5%).

In conclusion, long-term results after endovenous interventions remain poorly understood as few randomized studies have assessed outcomes beyond 2 years. Moreover, there is significant heterogeneity between studies in terms of intervention performed, patients treated, and outcomes reported. It should be recognized that superficial venous interventions can be offered in numerous ways, as not only are there various options for treating the GSV, but the timing and technique for treating varicosities may vary as well, as may the treatment location and type of anesthetic. In a clinical field where new treatment developments are frequently seen, a long-term study may be considered too ‘high-risk’ by researchers as the therapy assessed may be obsolete by the time the study is completed. Despite the practical and financial difficulties associated with randomized trials, it is encouraging that researchers continue to design, conduct, and publish new randomized trials. Rasmussen and colleagues recently published the results of a large randomized study (500 patients) comparing EVLA, RFA, UGFS, and surgical stripping ⁹. One-year results demonstrated that the highest technical failure rate was seen after UGFS, although longer term outcomes are awaited. The CLASS trial continues to recruit patients and numerous smaller studies are ongoing. However, meaningful meta-analysis of published studies is made virtually impossible by the enormous heterogeneity in reported outcomes. Only by improving the standardization of outcome reporting after endovenous interventions can the full clinical benefits of research be realized.

References:
1. Subramonia S, Lees T. Randomized clinical trial of radiofrequency ablation or conventional high ligation and stripping for great saphenous varicose veins. Br J Surg. 2010;97:328-336. [Randomized Controlled Trial].
2. Rasmussen LH, Bjoern L, Lawaetz M, Lawaetz B, Blemings A, Eklof B. Randomised clinical trial comparing endovenous laser ablation with stripping of the great saphenous vein: clinical outcome and recurrence after 2 years. Eur J Vasc Endovasc Surg. 2010;39:630-635. [Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't].
3. van den Bos R, Arends L, Kockaert M, Neumann M, Nijsten T. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg. 2009;49:230-239. [Comparative Study Meta-Analysis Review].
4. Winterborn RJ, Foy C, Earnshaw JJ. Causes of varicose vein recurrence: late results of a randomized controlled trial of stripping the long saphenous vein. J Vasc Surg. 2004;40:634-639. [Clinical Trial Randomized Controlled Trial].
5. Jia X, Mowatt G, Burr JM, Cassar K, Cook J, Fraser C. Systematic review of foam sclerotherapy for varicose veins. Br J Surg. 2007;94:925-936. [Research Support, Non-U.S. Gov't Review].
6. Belcaro G, Nicolaides AN, Ricci A, et al. Endovascular sclerotherapy, surgery, and surgery plus sclerotherapy in superficial venous incompetence: a randomized, 10-year follow-up trial–final results. Angiology. 2000;51:529-534. [Clinical Trial Comparative Study Randomized Controlled Trial].
7. Merchant RF, Pichot O. Long-term outcomes of endovenous radiofrequency obliteration of saphenous reflux as a treatment for superficial venous insufficiency. J Vasc Surg. 2005;42:502-509. [Multicenter Study].
8. Agus GB, Mancini S, Magi G. The first 1000 cases of Italian Endovenous-laser Working Group (IEWG). Rationale, and long-term outcomes for the 1999-2003 period. Int Angiol. 2006;25:209-215. [Clinical Trial Multicenter Study].
9. Rasmussen LH, Lawaetz M, Bjoern L, Vennits B, Blemings A, Eklof B. Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins. Br J Surg. 2011;98:1079-1087. [Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't].