Nonthermal Endovenous Procedures for Varicose Veins: A Health Technology Assessment

Abstract

Background: Varicose veins are part of the spectrum of chronic venous disease and are a sign of underlying chronic venous insufficiency. Treatments to address varicose veins include surgical vein removal under general anesthesia, or endovenous laser (EVLA) or radiofrequency ablation (RFA) under tumescent anesthesia. Two newer nonthermal endovenous procedures can close veins without any tumescent anesthesia, using either mechanochemical ablation (MOCA, a combination of mechanical and chemical techniques) or cyanoacrylate adhesive closure (CAC). We conducted a health technology assessment of these nonthermal endovenous procedures for people with symptomatic varicose veins, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding MOCA and CAC, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias or RoBANS tool, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Meta-analysis was conducted using Review Manager 5.2, where appropriate.We performed a systematic economic literature search and conducted a cost-utility analysis with a 5-year time horizon from the perspective of Ontario Ministry of Health. In our primary economic evaluation, we assessed the cost-effectiveness of nonthermal endovenous procedures (CAC and MOCA) compared with surgical vein stripping and thermal endovenous therapies (EVLA and RFA). We also analyzed the budget impact of publicly funding nonthermal and thermal endovenous therapies for adults with symptomatic varicose veins in Ontario over the next 5 years. Costs are expressed in 2020 Canadian dollars.To contextualize the potential value of nonthermal endovenous treatments, we spoke with 13 people with varicose veins who had sought various treatment options. We conducted phone interviews and qualitatively analyzed their responses regarding their care journey and the impact of different treatment options; the only nonthermal treatment that participants had experience with was CAC.

Results: We included 19 primary studies reported in 25 publications comparing either MOCA or CAC with at least one other invasive treatment for symptomatic varicose veins. No studies compared MOCA with CAC. Based on evidence of low to moderate quality, MOCA resulted in slightly poorer technical outcomes (vein closure and recanalization) than thermal endovenous ablation procedures. However, clinical outcomes, quality of life improvement, and patient satisfaction were similar compared with RFA (GRADE: Very low to Moderate) and EVLA (GRADE: High). Cyanoacrylate adhesive closure resulted in little to no difference in technical outcomes, clinical outcomes, and quality of life improvement compared with RFA and EVLA (GRADE: Moderate). Patient satisfaction may also be similar (GRADE: Low). Recovery time was slightly reduced with nonthermal endovenous procedures compared with thermal ablation (GRADE: Moderate). The effect of CAC compared with surgical vein stripping is very uncertain (GRADE: Very low). Major complications of any procedure were rare, with minor complications occurring as expected and resolving.We included two European studies in the economic evidence review that were partially applicable to the Ontario context. Both studies found that thermal ablation procedures (RFA, EVLA, or steam vein sclerosis) were the most cost-effective treatments, compared with surgical vein stripping and nonthermal therapies. Our cost-utility analysis showed that surgical vein stripping is the least effective and most costly treatment among five treatments for varicose veins. Differences in quality-adjusted life-years (QALYs) between endovenous treatments (CAC, MOCA, RFA, and EVLA) were small. When the willingness-to-pay (WTP) value was $50,000 per QALY gained, the probabilities of being cost-effective were 55.6%, 18.8%, 15.6%, 10.0%, and 0%, for EVLA, CAC, MOCA, RFA, and surgical vein stripping, respectively. When the WTP was $100,000 per QALY gained, the probabilities of being cost-effective were 40.2%, 30.0%, 17.7%, 12.1%, and 0%, for EVLA, CAC, RFA, MOCA, and surgical vein stripping, respectively. Publicly funding endovenous procedures (both nonthermal and thermal) would increase the total volume of treatments, resulting in a total 5-year budget impact of around $17 million.People with varicose veins with whom we spoke reported positively on their experiences with the CAC procedure and its outcomes. They also described geographic and financial barriers to accessing the range of available treatment options.

Conclusions: Cyanoacrylate adhesive closure and MOCA produced similar patient-important outcomes, and slightly shorter recovery compared with thermal ablation. Cyanoacrylate adhesive closure yielded similar anatomical outcomes as thermal endovenous ablation, but the technical outcomes of MOCA were slightly poorer.Compared with surgical vein stripping, all endovenous treatments were more effective and less expensive. If we were to look at the most cost-effective strategy (at WTP less than $100,000 per QALY), EVLA is most likely to be cost-effective. Assuming an 80% increase in the number of eligible people over the next 5 years, we estimate that publicly funding nonthermal and thermal endovenous treatments for varicose veins in Ontario would range from $2.59 million in year 1 to $4.35 million in year 5, and that the total 5-year budget impact would be around $17 million.For people with varicose veins, the CAC procedure was seen as a positive treatment method that reduced their symptoms and improved their quality of life.

Figure 1:. PRISMA Flow Diagram—Clinical Search Strategy

Figure 2:. Vein Closure in Randomized Controlled Trials Comparing Mechanochemical Ablation and Radiofrequency Ablation

Figure 3:. Vein Closure in Randomized Controlled Trials Comparing Mechanochemical Ablation and Endovenous Laser Ablation

Figure 4a:. Odds of Complete or Partial Recanalization of Treated Vein After Mechanochemical Ablation or Radiofrequency Ablation

Figure 4b:. Risk Difference for Complete or Partial Recanalization of Treated Vein After Mechanochemical Ablation or Radiofrequency Ablation

Figure 5a:. Odds of Complete or Partial Recanalization of Treated Vein After Mechanochemical Ablation or Endovenous Laser Ablation

Figure 5b:. Risk Difference for Complete or Partial Recanalization of Treated Vein After Mechanochemical Ablation or Endovenous Laser Ablation

Figure 6:. Vein Closure in Studies Comparing Cyanoacrylate Adhesive Closure and Radiofrequency Ablation

Figure 7:. Vein Closure in Studies Comparing Cyanoacrylate Adhesive Closure and Endovenous Laser Ablation

Figure 8a:. Odds of Complete or Partial Recanalization After Cyanoacrylate Adhesive Closure or Radiofrequency Ablation

Figure 8b:. Absolute Risk of Complete or Partial Recanalization After Cyanoacrylate Adhesive Closure or Radiofrequency Ablation

Figure 9a:. Odds of Complete or Partial Recanalization After Cyanoacrylate Adhesive Closure or Endovenous Laser Ablation

Figure 9b:. Absolute Risk for Complete or Partial Recanalization After Cyanoacrylate Adhesive Closure or Endovenous Laser Ablation

Figure 10:. PRISMA Flow Diagram—Economic Search Strategy

Figure 11:. Model Structure, Economic Evaluation of Endovenous Treatments for Varicose Veins

Figure 12:. Cost-Effectiveness Acceptability Curve: Treatments for Varicose Veins

Figure 13:. Cost-Effectiveness Plane: Incremental Costs and Incremental QALYs of Cyanoacrylate Adhesive Closure vs. Endovenous Laser Ablation

Figure 14:. Schematic Model of Budget Impact, Endovenous Procedures for Symptomatic Varicose Veins

Figure A1:. Risk Difference for Vein Closure in Randomized Controlled Trials Comparing Mechanochemical Ablation and Radiofrequency Ablation

Figure A2:. Risk Difference for Vein Closure in Randomized Controlled Trials Comparing Mechanochemical Ablation and Endovenous Laser Ablation

Figure A3:. Risk Difference for Vein Closure in Studies Comparing Cyanoacrylate Adhesive Closure and Radiofrequency Ablation

Figure A4:. Risk Difference for Vein Closure in Studies Comparing Cyanoacrylate Adhesive Closure and Endovenous Laser Ablation