Abstract: Ten reports of nine studies were identified following searching and three studies with a total of 233 participants met the inclusion criteria. Overall quality of evidence using the GRADE approach was low, predominantly due to the lack of both participant and researcher blinding in the included studies. The quality of the evidence was further limited as only three small studies contributed to the review findings. A subjective scoring system was used to obtain the symptoms of PTS so it was important that the assessors were blinded to the intervention. One study compared rutosides with placebo, one study compared rutosides with ECS and rutosides plus ECS versus ECS alone, and one study compared rutosides with an alternative venoactive remedy. Occurrence of leg ulceration was not reported in any of the included studies. There was no clear evidence to support a difference in PTS improvement between the rutosides or placebo/no treatment groups (OR 1.29, 95% CI 0.69 to 2.41; 164 participants; 2 studies; low-quality evidence); or between the rutosides and ECS groups (OR 0.80, 95% CI 0.31 to 2.03; 80 participants; 1 study ; low-quality evidence). Results from one small study reported less PTS improvement in the rutosides group compared to an alternative venoactive remedy (OR 0.18, 95% CI 0.04 to 0.94; 29 participants; 1 study; low-quality evidence). There was no clear evidence to support a difference in PTS deterioration when comparing rutosides with placebo/no treatment (OR 0.61, 95% CI 0.19 to 1.90; 80 participants; 1 study); with ECS (OR 0.61, 95% CI 0.19 to 1.90; 80 participants; 1 study); or an alternative venoactive remedy (OR 0.19, 95% CI 0.01 to 4.24; 29 participants; 1 study). No clear evidence of a difference in adverse effects between the rutosides and placebo/no treatment groups was seen ('mild side effects' reported in 7/41 and 5/42 respectively). In the study comparing rutosides with ECS, 2/80 could not tolerate ECS and 6/80 stopped medication due to side effects. The study comparing rutosides with an alternative venoactive remedy did not comment on side effects There was no evidence that rutosides were superior to the use of placebo or ECS. Overall, there is currently limited low-quality evidence that 'venoactive' or 'phlebotonic' remedies such as rutosides reduce symptoms of PTS. Mild side effects were noted in one study. The three studies included in this review provide no evidence to support the use of rutosides in the treatment of PTS.

Plain-language summary: This review aimed to evaluate the existing literature to see if rutosides were useful for treating PTS. We also investigated whether there were any side effects from the treatment. We searched all existing databases for trials relating to the use of rutosides for the treatment of PTS following DVT (current until 21 August 2018). Two review authors independently assessed the trials for inclusion and extracted results in line with our prescribed criteria. We found three suitable trials, with a total of 233 patients, and six unsuitable trials that were not included in the review. The studies were small and undertaken very differently meaning they could not be combined. The studies used different comparisons with rutosides (placebo (inactive product), compression stockings alone or combined with rutosides, or hidrosmina (a venoactive drug, which acts on the vascular system). They also used different doses of rutosides (900 mg/day to 2000 mg/day). We found no clear evidence from any of the trials that treatment with rutosides improved symptoms and signs of PTS; or that there was any difference in side effects. Occurrence of leg ulceration was not reported in any of the included studies. Overall quality of evidence, using the GRADE approach, was low mainly due to the lack of both participant and researcher blinding. This means both investigators and participants knew what drug they were getting and this can effect the results. The quality of the evidence was further limited as only three small studies contributed to the review findings. A subjective scoring system was used to obtain the symptoms of PTS so it was important that the assessors were blinded to the intervention.