Chronic venous insufficiency
A spectrum of conditions with impaired lower-limb venous return: from telangiectasias and leg heaviness (CEAP C0s–C2) to edema, trophic skin changes, and ulcers (C3–C6). ESVS 2022 guidelines build treatment around compression therapy, lifestyle change (weight reduction, physical activity), and where indicated, varicose-vein procedures (sclerotherapy, endovenous laser or radiofrequency ablation). Venoactive drugs (diosmin/hesperidin, hidrosmin, troxerutin) are symptomatic adjuncts; the 2020 Cochrane meta-analysis showed modest reduction in edema and pain, without effect on disease progression.
ICD-10 I87.26 drugs
Also known as: CVI, Chronic venous disease, Venous reflux disease
Drugs used for this condition
- CBilberry (Vaccinium myrtillus fruit extract)Add-on therapy · Herbal preparation, EMA HMPC traditional herbal medicinal productBilberry fruit extract received EMA HMPC traditional-use status in 2015 for mild symptoms of chronic venous insufficiency – heavy and painful legs, oedema. The decision rests on 30 years of European use, not on large RCTs. The Cochrane review 2018 of herbal extracts in CVI found very low-quality evidence for bilberry anthocyanosides – the effect on symptoms is small and the difference vs placebo is clinically marginal. Spanish AEEV considers compression stockings and micronised diosmin/hesperidin first-line. If a clinician prescribed bilberry extract as monotherapy for CVI, consider seeking a second opinion – the efficacy is weakly supported. Add-on use with compression for mild symptoms is reasonable, but it does not replace compression therapy.
- CPycnogenol (French maritime pine bark extract, Pinus pinaster)Add-on therapy · Plant polyphenol complex, supplement. Standardised maritime pine bark extract with 65–75% oligomeric proanthocyanidinsPycnogenol is one of the few supplements with relatively convincing evidence in chronic venous insufficiency. The Belcaro group RCT series (2006–2014) in 400 patients with CEAP C3–C4 CVI showed reduced leg oedema, CEAP severity and improved microcirculation at 150–300 mg/day × 8 weeks vs placebo. Cochrane 2012 (Schoonees) included 15 RCTs in 800 patients: pycnogenol showed moderate advantage over placebo in CVI, but most studies have limited methodology. ESVS 2022 lists compression stockings 23–32 mmHg and micronised diosmin/hesperidin (Detralex/Daflon) first-line for CVI; pycnogenol is mentioned as an option with limited evidence. Avoid in pregnancy with varicose veins and patients on anticoagulants.
- DCalcium dobesilateAdd-on therapy · Capillary-stabilizing and venoactive agentUsed symptomatically for leg heaviness, edema, and pain in chronic venous insufficiency CEAP classes C0s–C3. Evidence is weak: the 2020 Cochrane meta-analysis of flavonoid and non-flavonoid venoactive agents reported moderate effect on pain and edema with low certainty. No benefit on hard outcomes (venous ulcer healing, disease progression) has been described. ESVS 2022 international guidance does not place this drug among first-line agents – the base treatment is compression and lifestyle change.
- DDiosmin/hesperidinAdd-on therapy · Micronized purified flavonoid fraction, «venoactive» agentUsed symptomatically for leg heaviness, edema, and pain in chronic venous insufficiency CEAP classes C0s–C3. Evidence is modest: the 2020 Cochrane meta-analysis of flavonoids showed moderate effect on pain and edema with low certainty. No effect has been described on hard outcomes (disease progression, venous ulcer healing) apart from a small effect on venous ulcer healing alongside compression. ESVS 2022 foundation therapy is compression and lifestyle change; diosmin/hesperidin does not replace them.
- DHidrosminAdd-on therapy · Bioflavonoid, «venoactive» agentUsed symptomatically for leg heaviness, edema, and pain in chronic venous insufficiency CEAP classes C0s–C3. Evidence is weak: Spanish trials from the 1990s showed modest symptom and calf-circumference reduction, but no independent large RCTs or meta-analyses exist. The 2020 Cochrane review of flavonoids overall noted modest effects on pain and edema with very low certainty. Foundation therapy is compression and lifestyle change; hidrosmin does not replace them and does not affect disease progression. The ESVS 2022 international guideline does not mention this drug.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit