*2.2.1.6.1. Dabigatran*

A systematic review and meta-analysis was performed with the aim of summarizing all available evidence from high-quality real-world observational studies regarding efficacy and safety of non–vitamin-K oral anticoagulants compared with vitamin-K antagonists in patients with atrial fibrillation [36]. Compared with warfarin, dabigatran is associated with lower risk for intracranial hemorrhage in several studies that included 606.855 patients (hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.37–0.49) and lower risk for death in 319.486 patients (HR, 0.63; 95% CI, 0.52–0.76). There is no statistical difference between dabigatran and warfarin for the outcomes of ischemic strokes (HR, 0.96; 95% CI, 0.80–1.16); ischemic stroke or systemic embolism (HR, 1.17; 95% CI, 0.92–1.50); any stroke or systemic embolism (HR, 0.93; 95% CI, 0.77–1.14); major hemorrhage (HR, 0.83; 95% CI, 0.65–1.05); and myocardial infarction (HR, 0.96; 95% CI, 0.77–1.21). Authors identified 10 studies that included 537.770 patients which assessed the outcome of gastrointestinal hemorrhage and reported higher risk of dabigatran compared with warfarin (HR, 1.20; 95% CI, 1.06–1.36). Authors also reported the presence of a significant heterogeneity in all analyses with the exception of the outcome of intracranial hemorrhage and any stroke or systemic embolism.

#### *2.2.1.6.2. Rivaroxaban*

As reported in the study authored by Ntaios and Colleagues [36], compared with warfarin, rivaroxaban is associated with lower risk for intracranial hemorrhage in several real-world studies that included 136,221 patients (HR, 0.64; 95% CI, 0.47–0.86). There is no statistical difference between rivaroxaban and warfarin for the outcomes of ischemic stroke (HR, 0.89; 95% CI, 0.76–1.04); ischemic stroke or systemic embolism (HR, 0.73; 95% CI, 0.52–1.04); any stroke or systemic embolism (HR, 0.87; 95% CI, 0.71–1.07); major hemorrhage (HR, 1.00; 95% CI, 0.92–1.08); myocardial infarction (HR, 1.02; 95% CI, 0.54–1.89); and death (HR, 0.67; 95% CI, 0.35–1.30). Authors identified four studies that included 71.368 patients which assessed the outcome of gastrointestinal hemorrhage and reported higher risk of rivaroxaban compared with warfarin (HR, 1.24; 95% CI, 1.08–1.41). Authors reported a significant heterogeneity for the outcomes of intracranial hemorrhage and death.

concomitant treatment with P-gp inhibitors. The most common adverse reactions (≥5%),

Real-World Safety of Anticoagulants http://dx.doi.org/10.5772/intechopen.78023 91

Sulodexide belongs to a class of substances known as glycosaminoglycans (GAGs), composed of a fast-moving heparin fraction (80%) with affinity for antithrombin III and a dermatan

Sulodexide exerts a strong antithrombotic activity by simultaneously potentiating the antiprotease activities of both antithrombin III and heparin cofactor II. Sulodexide also has a profibrinolytic effect (through activation of tissue plasminogen activator and inhibition of plasminogen activator inhibitor), an antiproliferative effect on smooth muscle cells, and anti-

Several clinical studies have demonstrated the efficacy of sulodexide in the treatment or prevention of vascular diseases associated with increased thrombotic risk, such as peripheral arterial occlusive diseases, post-myocardial infarction, recurrent DVT, and postthrombotic syndrome [42]. Other clinical applications are treatment of venous ulcers, cerebrovascular disorders, diabetic nephropathy, and other diabetic complications (nephropathy and macular edema).

Sulodexide is available for both intravenous and intramuscular administration, but it can be taken also orally. By the oral route, Sulodexide is absorbed within 1–2 hours and behaves as a mono-compound, reaching the time to peak in about 4 hours with a dose of 50–100 mg. Similar concentrations are maintained at least up to 18 hours. The distribution volume is very large, due to a higher affinity of sulodexide for the extensive surface area of the endothelium rather than for plasma proteins. Metabolism is liver dependent and based on N-desulfation,

Nowadays, sulodexide 250 LSU (lipasemic unit) capsules or 600 LSU parenteral preparation is approved only in Europe (Italy) for venous chronic ulcers in adults (250 LSU twice daily,

Oral administration could lead to disorders of the gastrointestinal system with nausea, vomit-

observed in the APEX trial considered for approval, were related to bleeding.

sulfate fraction (20%) with affinity for heparin cofactor II.

lipemic and antiatherosclerotic effects [40, 41].

while excretion is mostly kidney dependent [40, 43].

*2.2.3. Sulodexide*

*2.2.3.1. Mechanism of action*

*2.2.3.2. Indications*

*2.2.3.3. Pharmacokinetics*

*2.2.3.4. Therapy management*

away from meals).

ing, and heartburn.

*2.2.3.5. Safety*
