Systematic literature review and network Meta-analysis of sulodexide and other drugs in chronic venous disease

Abstract

Objective To assess the clinical efficacy of sulodexide, including a comparison with venoactive drugs (VAD) (micronized purified flavonoid fraction, MPFF; hydroxy-ethyl-rutosides, HR; calcium dobesilate;Ruscus extract combined with hesperidin methyl chalcone and vitamin C, Ruscus+HMC+VitC; horse chestnut seed extract, HCSE) and pentoxifylline in patients with chronic venous disease. Methods We performed a literature search in MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) and observational studies. Proportion of patients with complete venous ulcer healing was the primary outcome and lower leg volume, foot volume, ankle circumference and symptoms were the secondary outcomes. Bayesian network meta-analysis (NMA) was perfomed with random effects models using only RCTs. A meta-analysis of observational studies was performed for sulodexide because no RCT could be included in NMA for symptoms or signs. Results Forty-five RCTs and eighteen observational studies were identified. Sulodexide was included only in a single NMA for the proportion of patients with complete ulcer healing and it showed to have the highest probability of being the best treatment (48%) compared with pentoxifylline (37%) and MPFF (16%). MPFF was the most effective treatment in reducing lower leg volume, CIVIQ-20 score and pain VAS scale while calcium dobesilate and Ruscus+HMC+VitC were the most effective in reducing foot volume and ankle circumference respectively. Meta-analyses of observational studies for sulodexide showed that it improves significantly the scoring of pain, feeling of swelling, heaviness and parasthesiae measured by Likert scales. Conclusions Sulodexide is at least as effective as pentoxifylline and more effective than MPFF in improving the rate of ulcer healing in patients with CVD. VADs are effective in improving venous symptoms and signs, as was also shown by sulodexide in the meta-analysis of observational studies. The relative effectiveness of sulodexide and VADs needs to be evaluated by an RCT in order to better inform clinical practice.

Management of Trigeminal Autonomic Cephalalgias Including Chronic Cluster

“…A meta-analysis of the 2 open-label studies investigating verapamil showed that 87% of patients either had complete elimination of cluster attacks or a 50% or greater reduction in attack frequency. 53 The Danish Headache Center observed a 44% efficacy for the end point of more than 50% attack reduction in 146 patients with chronic cluster headache. 34 One underpowered study compared lithium and placebo for the prevention of cluster attacks.…”

“…A meta-analysis of 3 open studies with a total of 103 patients found that lithium was effective in inducing cluster remission or reducing attack frequency by at least 50% in 77% of patients. 53 In patients treated with lithium, plasma levels should be monitored on a regular basis due to the potential toxicity of the drug.…”

No More Venous Ulcers—What More Can We Do?

“…Sulodexide, a drug combining low-molecular-weight heparin and dermatan sulfate with profibrinolytic and antithrombotic effects, was demonstrated to improve the VLU healing rate in a randomized multicentric placebo-controlled trial that enrolled 235 patients treated for three months [117]. More recent papers and meta-analyses confirm the effectiveness of sulodexide in VLU healing [118,119]. Also, a recent Cochrane review reports positive effects of sulodexide in VLU patients but also highlights that "the evidence is only low quality and the conclusion is likely to be affected by new research", and that "Further rigorous, adequately powered RCTs examining the effects of sulodexide on healing, ulcer recurrence, quality of life and costs are necessary" [120].…”

Chronic venous ulcers with different approaches for treatment

“…An open skin lesion on the leg that doesn't reflect any signs of healing spontaneously is known as a venous leg ulcer (VLU) and arises from a region where ambulatory venous hypertension is present [2] . They represent around 80% of all lower extremity ulcers, and between 1and 2 percent of the population will get a chronic venous ulcer (CVU) at some point in their lives [3] . Clinical symptoms, etiological variables, the anatomical spread of the disease, and the pathogenic mechanism underlying the disease are all used to classify CVDs in the Comprehensive Classification System for Chronic Venous Disorders (CEAP) [4] .…”