The role of venoactive drugs in a modern treatment paradigm: evidence review.

Chronic venous disease (CVD) causes substantial symptom burden and healthcare cost, driven not only by venous hypertension but by a persistent molecular cascade of endothelial activation, glycocalyx degradation, and inflammation within the vein wall. Venoactive drugs (VADs) - a heterogeneous class of flavonoid, synthetic, animal-derived, and plant-derived compounds - target this cascade and are recommended by international guidelines as adjuncts to compression therapy, endovenous intervention, and wound care in venous leg ulcer (VLU) management. This review synthesizes the pharmacological rationale and clinical evidence for VADs across these three adjunct settings. The evidence base is strongest for VAD use alongside compression, supported by multiple Cochrane-grade meta-analyses; MPFF and ruscus extracts have the most robust symptom evidence, while MPFF, pentoxifylline, and sulodexide have the strongest evidence for VLU healing. Evidence in the peri-interventional setting remains the weakest, limited to open-label studies of MPFF. Priorities for future research include stratified and biomarker-guided prescribing, combination pharmacotherapy, and larger, adequately powered VLU healing trials.