Approach
Graded compression stockings are the cornerstone of CVI treatment, supplemented by further specialised procedures, the choice of which depends on the specific associated clinical features.
Compression
The mainstay of treatment for CVI-related oedema, stasis dermatitis, and small venous leg ulcers is the use of graded compression knee-high stockings.[2][19][20]
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[Figure caption and citation for the preceding image starts]: Serial images of recurrent venous ulcer with resolution at 3 monthsFrom the collection of Dr Joseph L. Mills; used with permission [Citation ends].
As therapy may be lifelong, patient adherence is of critical importance. An estimated 30% to 65% of patients are non-adherent with compression therapy. Recurrence of venous leg ulcers in patients adherent with stocking use is half that in those who are non-adherent. Non-adherence with prescribed stockings is the primary cause of compression therapy failure.[21]
In Cochrane reviews, compression stockings were more effective in healing venous ulcers than no compression therapy.[22][23] [
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For ulcer healing, multilayer dressings are more effective than single-layer dressings.[24] A single randomised controlled study suggested that 'progressive' stockings, which progressively apply maximal compression (23 mmHg at the level of the calf vs. 10 mmHg at the ankle), were superior to a 'degressive' stocking (30 mmHg at ankle vs. 21 mmHg at upper calf). The outcome measure used was a composite consisting of improvement in pain, deep and/or superficial venous thrombosis, pulmonary embolus (PE), and ulceration of skin.[15]Stockings must be put on first thing in the morning and should be removed only when the patient is recumbent (usually just before going to bed).
There are three classes of compression stockings: class 1 stockings (low compression) control oedema; class 2 (medium compression) and class 3 (high compression) are usually required for more advanced CVI.
Thromboembolic disorder (TED) stockings are inadequate for controlling CVI and should not be prescribed for this condition because the pressure at the ankle is insufficient at less than 20 mmHg.
Patients with severe CVI or previous ulcers generally require lifelong graded compression stockings of ≥30 to 40 mmHg.
Intermittent pneumatic compression may also be considered in patients with post-thrombotic syndrome, to reduce severity.[2]
Pharmacotherapy
Eczematous skin changes and mild stasis dermatitis
It is generally felt that applying a simple moisturising cream to combat skin dryness and flaking is beneficial.
Venous leg ulcers
Long-term therapy with non-specific local unguents or topical antibiotic ointments or creams is of no benefit and may damage adjacent skin. The use of such therapies is also strongly discouraged because of allergic reactions and the potential for breakdown of the dermal barrier.
Pentoxifylline and micronised purified flavonoid fraction (MPFF) have shown some benefit in venous leg ulcer healing in randomised clinical trials.[25] [
]
Pentoxifylline is used to treat claudication. A meta-analysis of five trials showed a minimal benefit to venous leg ulcer healing with oral pentoxifylline (odds ratio 1:3) compared with compression therapy and placebo.[26] [
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A meta-analysis of prospective randomised trials of MPFF in the treatment of venous leg ulcer compared compression and local care with and without the addition of oral MPFF.[27] At 6 months, the chance of ulcer healing was 32% better in patients treated with adjunctive MPFF than in those managed by conventional therapy alone (relative risk reduction 32%, 95% CI 3% to 70%). This difference was present from month 2 (relative risk reduction 44%, 95% CI 7% to 94%) and was associated with a shorter time to healing (16 weeks vs. 21 weeks; P=0.0034). These data suggest that MPFF may be a useful adjunct to conventional therapy in large and long-standing venous leg ulcers. Diosmin (an MPFF) is available in some European, Asian, and South American countries and in Canada, but not in the US or the UK.
One systematic review determined that, while data were limited by heterogeneity and small sample sizes, pentoxifylline and micronised purified flavonoid fraction (MPFF) were both reported to have demonstrated clinical benefits when used In conjunction with compression therapy.[28]
The following systemically given drugs are ineffective in healing venous leg ulcers: aspirin, ifetroban, stanozolol, antibiotics, and hydroxyrutosides.
Topically applied growth factors have not been systematically shown to be efficacious in speeding up venous leg ulcer healing.
Leg pain
Where available, venoactive drugs, such as diosmin, can also be considered for the treatment of CVI pain.[2]
Invasive procedures
Superficial venous reflux
Saphenectomy: a randomised controlled trial of saphenectomy (surgical stripping) and compression versus compression alone in patients with significant reflux in the great or small saphenous vein on duplex ultrasound showed 89% to 93% initial ulcer healing rates in both groups (P value reported as not significant). Ulcer recurrence rates at 4 years were 52% in the compression-only group compared with only 24% in those who underwent saphenectomy and compression, a difference that was statistically significant.[29] These findings strongly suggest that saphenectomy confers long-term benefit in patients with CVI who also have superficial venous reflux.
Endovenous laser therapy or radiofrequency ablation of the great saphenous vein (GSV): these procedures can be done with outpatients under local tumescent anaesthesia and have generally replaced surgical stripping for most patients requiring GSV ablation. Following endovenous ablation, compression stockings should be worn for 24 hours per day for 1-3 days, then during the day for 1-2 weeks. Postoperatively, normal activities can be resumed, but strenuous leg activity (e.g., running, weighted leg exercises, cycling) should be avoided for 1 week. Continued use of compression stockings during the day is recommended following ablative procedures on the superficial system if there is ongoing evidence of reflux (i.e., deep system insufficiency). A randomised controlled trial comparing endovenous laser ablation therapy with saphenopopliteal junction ligation plus attempted stripping/excision for the treatment of small saphenous vein insufficiency has reported similar 2-year outcomes, but with the possible benefit of fewer short-term sensory deficits with endovenous laser ablation therapy.[30] Early endovenous ablation of the superficial venous reflux (within 2 weeks) has been found to result in faster healing of venous leg ulcers and more time free from ulcers than deferred endovenous ablation (considered after ulcer was healed or at 6 months if ulcer was not healed).[31]
Foam sclerotherapy: this technique can also be used to ablate the GSV.[32] The sclerosant agent is mixed with air to produce foam, which is then injected into the vein under ultrasound guidance. The foam displaces blood in the vein and causes spasm of the vein and endothelial injury, resulting in thrombosis of the vessel. Retinal or cerebral emboli (causing migraine but rarely stroke) may occur with the use of foam in 2% to 6% of patients, but these adverse sequelae are almost always minor and transient.[33]
A meta-analysis of over 12,000 legs investigated the success rate of these therapies as determined by duplex ultrasound, documenting successful vein excision or ablation and lack of residual reflux.[33] Measured in this manner, after a mean follow-up of 32 months, the relative effectiveness rates were 77% for foam sclerotherapy, 78% for surgical stripping, 84% for radiofrequency ablation, and 94% for laser ablation. The major complication of these techniques was DVT, occurring in 1% to 3% of patients. Individualised thromboprophylaxis strategies should be considered.[2]
Angiomata and varicosities
These lesions may occasionally cause symptoms of sufficient severity to warrant laser or radiofrequency ablation or injection sclerotherapy, which may be liquid or, increasingly, foam sclerotherapy. It should be noted that foam sclerotherapy is not approved in all countries for this use.
Perforating vein incompetence
Incompetent perforating veins may be treated with endovenous ablation (laser or radiofrequency) or ligation.[2]
Iliac vein obstruction
An important subset of patients with CVI have iliac vein obstruction, more commonly on the left side than the right. In selected patients (determined by a vascular specialist), symptoms may be substantially improved by percutaneous iliac angioplasty and stenting. These procedures are performed in significant numbers only in selected centres, and the indications for such procedures are still developing.[34]
Deep venous reflux
Venous valvular reconstruction (either with leaflet repair or with axillary valve transplantation) is rarely performed, and its use is generally confined to selected centres. Results are far better when performed in patients with primary rather than post-thrombotic venous reflux.[35] The operation is generally reserved for patients in whom conventional therapy has failed.
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