Abstract
BACKGROUND: Chronic venous disease (CVD) is a major global health issue, affecting millions of people and contributing to significant morbidity and economic strain. The condition's pathophysiology is complex, involving both mechanical and biochemical processes that lead to venous reflux, obstruction, and chronic inflammation. This review focuses on the role of venoactive compounds (VACs), also known as venoactive drugs in Europe and other parts of the world, in managing CVD. The aim was to review the scientific evidence and to define the role of VACs within the comprehensive treatment algorithm for CVD, alongside established and well adopted interventional therapies and noninterventional therapies such as compression. METHODS: The review of the scientific evidence was done on VACs mechanism of action and efficacy in alleviating CVD symptoms, reducing swelling or venous edema, and improving healing of venous leg ulcers. Whenever available, systematic reviews, meta-analyses and randomized controlled trials were used. The quality of evidence assessment followed the GRADE methodology from A (high), B (moderate), to C (low to very low) quality. RESULTS: Venoactive drugs or compounds share similar effects, such as sealing the endothelial barrier, enhancing lymphatic drainage, reducing edema, improving venous tone, inhibiting leukocyte adhesion to vein walls/valves and inflammatory mediator release, lowering blood viscosity, and promoting red blood cell flexibility. Scientific evidence on the VACs effectiveness on CVD symptoms (pain, cramps, and heaviness) and swelling or edema have shown some variability. Micronized purified flavonoid fraction (MPFF) and Ruscus extract combined with hesperidin methyl chalcone and ascorbic acid had the highest, mostly level A, quality of evidence. In venous leg ulcers, micronized purified flavonoid fraction, sulodexide, and pentoxifylline were the most effective adjunctive treatments, with evidence level A. CONCLUSIONS: The existing scientific evidence provides a strong rationale for incorporating VACs into a comprehensive treatment plan for CVD, alongside established interventional therapies and noninterventional approaches like compression, to optimize patient outcomes and improve quality of life.