Thigh-high lower limb elastic compression stockings (ECS) did not reduce cumulative vasovagal syncope (VVS) recurrence, change VVS-free survival or reduce the frequency of multiple VVS episodes in adults who had experienced two or more VVS, according to COMFORTS-II trial results published Aug. 4 in JACC.

In the multicenter randomized sham-controlled trial, the first of its kind, Hamed Tavolinejad, MD, et al., randomized 266 participants (mean age 39 years, 58% women) with two or more previous VVS episodes within the past year and a Calgary Syncope Symptom Score of ≥ –2 to either thigh-high, open-toe active ECS that provide 25-30 mm Hg pressure to the leg or identical-looking sham ECS that provide ≤10 mm Hg pressure in addition to standard care without medications. Participants had a median of three VVS episodes in the past year and four overall, with their first episode occurring at a mean age of 32 years.

Results at 12 months showed that VVS recurred in 29% of participants (39/134) in the treatment group and 35% of participants (46/132) in the control group (absolute risk reduction, 5.7%; p=0.315). VVS-free survival was not significantly different between groups (hazard ratio, 0.81; p=0.333). The median number of recurrent episodes was similar as well (2.5 for treatment vs. 2.0 for sham; p=0.839).

ECS adherence was "suboptimal," according to investigators, with discontinuation rates of 37% in the treatment arm and 35% in the control arm. Adherence had no significant interaction with treatment outcomes (p=0.810).

Outside of the primary outcomes, investigators note that significantly fewer VVS episodes occurred while participants were actively wearing ECS (323% vs. 45%; p=0.024), and there was a significant interaction between a higher number of prior VVS episodes and greater treatment effectiveness (log-hazard coefficient = –0.03; p=0.011).

They write that both outcomes leave room "for speculation on potential symptomatic benefits in carefully selected patients with more frequent recurrences in whom the main trigger is prolonged standing."

Additionally, "this study does not rule out the utility of more extensive compression therapy targeting pelvic and splanchnic mesenteric venous pooling such as waist-high compression garments and abdominal binders," they continue.

In an accompanying editorial comment, Albert Y. Liu, MD, MPH, and Cara N. Pellegrini, MD, note that thigh-high garments may simply not be high enough. The study may also have been underpowered, focusing on a lower risk group with major adherence difficulties.

"There may still be hope," they conclude, writing that "Compression therapy remains a mechanistically sound concept, and thoughtful stratification of VVS phenotypes and innovation in compression strategies may yet yield meaningful benefit for those most in need."