Comparative Efficacy and Safety of Sulodexide and Other Extended Anticoagulation Treatments for Prevention of Recurrent Venous Thromboembolism: A Bayesian Network Meta-analysis

Abstract

Objective This network meta-analysis (NMA) assesses the clinical comparative efficacy and safety of sulodexide versus direct-acting oral anticoagulants (DOACs), vitamin K antagonist (VKA), and aspirin in patients with an unprovoked venous thromboembolism (VTE). Methods We conducted a literature search in MEDLINE, Embase, and Cochrane Library using both randomized controlled trials (RCTs) and observational studies. Reduction in recurrent deep venous thrombosis (r-DVT), pulmonary embolism (PE), major bleeding (MB), clinically relevant nonmajor bleeding (CRNMB) were the primary efficacy and safety outcomes. Other secondary end points were also included. We performed a fixed, random effects, and hierarchical models Bayesian NMA for each outcome. Results We identified 18 RCTs and seven observational studies. Random models showed sulodexide is the best treatment compared with DOACs, VKA, and aspirin at reducing the risk of CRNMB, for preventing death from any cause, and VTE/PE/myocardial infarction (MI)/stroke with 0.47, 0.81, and 0.65 probabilities, respectively. In the random model sulodexide was the best treatment for reducing the risk of MB with a 0.50 probability and hierarchical model that confirmed favorable results. Random and hierarchical models showed sulodexide and DOACs to be the best treatments for reducing PE risk. Sulodexide was more effective than aspirin for reducing r-DVT with 0.12 and less of 0.0001 probabilities, respectively. Conclusion Sulodexide is more effective for reducing MB and CRNMB, for preventing deaths from any cause, and from VTE/PE/MI/stroke, than other treatments, for both random and hierarchical models. Sulodexide showed to be more effective than aspirin in reducing the risk of r-DVT and PE. Sulodexide's reduction in bleeding while protecting from recurrent DVT risk makes this therapeutic option an important alternative for extended anticoagulation treatment.

Sulodexide in the treatment of patients with early stages of COVID-19: a randomised controlled trial

“…Of the 312 patients randomised for group allocation, 31 patients reported a negative COVID- 19 (Table 3).…”

“…The emergence of the novel coronavirus disease 2019 (COVID- 19) developed into a pandemic that changed our way of life to a degree yet to be determined. The reported percentage of infected patients who need hospital care is between 15-25%.…”

“…The improvement of the glycocalyx integrity not only restores the endothelium barrier function, it also allows the endothelium to better modulate the generation of key inflammatory molecules, such as IL1β, IL6, IL8 and TNFα, while also downregulating its response to them 16,17 . The heparin compound adds an antithrombotic and profibrinolytic effect that may be important against the procoagulant state caused by SAR-CoV-2; moreover, it may exert added anti-inflammatory effects 18,19 .…”

Sulodexide in the Treatment of Patients with Early Stages of COVID-19: A Randomized Controlled Trial

“…[35] [36] Sulodexide modulates and inhibits the generation of free radicals and critical inflammatory molecules, such as interleukin (IL)-1 beta (β), IL-6, IL-8 and tumor necrosis factor alfa (TNF α). [37] [38] Although sulodexide's effect in modulating the glycocalyx can take time, its impact on modulating the endothelial response to these molecules (particularly IL6, which is very relevant in COVID- 19) can occur in as little as 24hrs. [34] This effect could help explain the reduced need for hospital care and supplemental oxygen observed in the sulodexide group.…”

“…Finally, sulodexide is also associated with a lower bleeding risk than is seen with other oral anticoagulants. [19] Reports suggest low molecular weight heparin (LMWH) is accompanied by a reduction in mortality when used in a hospital setting. [20] It has been hypothesized on this basis that patients on chronic anticoagulation may experience lower incidences of thromboembolic events upon hospitalization for COVID-19; thus, research into its outpatient use in ameliorating the disease's clinical course has been proposed.…”