UTILITY OF VENOACTIVE COMPOUNDS IN POST-THROMBOTIC SYNDROME: A SYSTEMATIC REVIEW.

Abstract

Background: Post-thrombotic syndrome (PTS) has been highly prevalent, over 50% of the patients develop PTS following lower extremity acute deep vein thrombosis (DVT). Venoactive compounds (VACs) have been recommended for decades for patients with chronic venous insufficiency (CVI), including PTS. The objective of our study was to perform a systematic review to determine the quality of evidence on the utility of VACs for both prevention and treatment of PTS.

Methods: A systematic review was conducted searching the literature between 1/1/1980 and 7/14/2023 for venoactive drugs or medications, DVT and PTS using PubMed, Medline, life science journals and Cochrane library. Only randomized controlled trials (RCTs) published in English were included in this review. The PRISMA Guidelines and the revised Cochrane risk-of-bias tool for RCTs were used.

Results: Ninety-four references were identified, eleven RCTs fulfilled the inclusion criteria. VAC's administered were diosmin, hidrosmin/rutosides, micronized purified flavonoid fraction (MPFF), and sulodexide. The studies included a highly variable proportion of patients with PTS (8.6% to 100%). Some older studies omitted details of the methodology. Two studies suggested benefit of diosmin and MPFF as adjunctive treatment to rivaroxaban in the prevention of PTS and showed low or unclear risk of bias. Evaluation of RCTs for treatment of post-thrombotic CVI found low or unclear risk of bias in 81.6% to 85.7%. All studies suggested that VACs were beneficial for PTS treatment, they improved venous symptoms, decreased edema, and aided healing of venous ulcers.

Conclusions: This systematic review found that VACs had at least moderate quality of evidence in improving venous symptoms, decreasing edema, and accelerating venous ulcer healing. Two pilot RCTs of higher quality suggested usefulness of diosmin and MPFF as adjunctive treatment to rivaroxaban therapy to reduce the incidence of PTS and improve deep vein recanalization. Since most RCTs were published over two decades ago, and several lacked the required precision in reporting, new high quality, low bias RCTs are needed to assess the role of specific VACs for both prevention and treatment of PTS.