For patients with first-time unprovoked venous thromboembolism (VTE), oral sulodexide may help stave off future flare-ups without causing serious safety risks, suggests new research published online September 25, 2015 in Circulation..
The multicenter Sulodexide in Secondary Prevention of Recurrent Deep Vein Thrombosis (SURVET) study included 615 patients. After receiving and completing standard anticoagulant treatment, 4.9% of those who then received 500 lipasemic units of sulodexide twice daily for 2 years had a recurrence of VTE, the primary outcome, vs 9.7% of those who received matching placebo (P=0.02).
Although there were no reports of major bleeding events, four patients did have clinically relevant nonmajor bleeding episodes (two in each treatment group).
The investigators, led by Dr Giuseppe M Andreozzi (University Hospital, Padua, Italy), note that because VTE often returns after initial treatment with a vitamin-K antagonist (VKA) they wanted to see if sulodexide, along with compression therapy, could effectively stop that—which it did.
“Future investigations should examine whether a similar effect can be obtained after treatment of the index event with non-VKA oral anticoagulants, whether there is a summation of effects with aspirin . . . and whether specific subgroups are more or less likely to benefit from sulodexide or other treatments,” they write.
According the investigators, sulodexide is a natural glycosaminoglycan with antithrombotic and profibrinolytic activities and affects the normal hemostasis to a lower extent than heparin, with a very low risk of bleeding. The drug consists of low-molecular-weight heparin and dermatan sulfate.
All SURVET participants had either a documented unprovoked first deep vein thrombosis (DVT) (92%) or pulmonary embolism (PE) (8%) and received 3 to 12 months of treatment with a VKA at one of 43 centers in seven European countries.
After VKA discontinuation, they were randomly assigned to receive for 2 years either sulodexide capsules (n=307; 57% men; mean age 55.7 years) or placebo (n=308; 50% men; mean age 55.9 years). All participants were also instructed to wear elastic stockings throughout the study period. Although in-center exams were performed every 3 months, patients were told to report immediately if they had any symptoms that might suggest VTE or bleeding events.
A total of 15 members of the sulodexide group and 30 members of the placebo group had VTE recurrence, for a hazard ratio (HR) of 0.49 (95% CI 0.27–0.92). This included 12 episodes of DVT in the sulodexide group and 24 episodes in the placebo group and three and six PEs, respectively.
After adjustment for factors such as age, sex, and duration of VKA exposure, the sulodexide group was still significantly more likely to have a reduced risk of recurrence (HR 0.45, 95% CI 0.24–0.84; P=0.01).
When the researchers examined factors independently, age was found to be significantly associated with an increased risk for VTE recurrence (HR 1.33 per decade, 95% CI 1.06–1.65; P=0.01), as was being male (HR 2.45, 95% CI 1.25–4.78; P=0.01).
Deaths included one from stroke in the active-treatment group and three in the placebo group (two from ACS and one from lower-limb ischemia). There were no significant group differences in patients reporting at least one nonserious or serious adverse event or at least one adverse event causing study or treatment discontinuation.
“Sulodexide given after discontinuation of anticoagulant treatment reduced the risk of recurrence in patients with unprovoked [VTE], with no apparent increase of bleeding risk,” write the investigators.
Limitations cited included a higher-than-expected number of premature study interruptions by patients (11 of the active-treatment group, 18 of the placebo group) and a low number of qualifying events, especially patients who had PE as their index event (7.6%). “The results of this study should therefore be considered poorly applicable to this specific subpopulation,” write the researchers.
Source: Andreozzi GM, Bignamini AA, Davi G, et al. Sulodexide for the prevention of recurrent venous thromboembolism: The SURVET study: A multicenter, randomized, double-blind, placebo-controlled trial. Circulation 2015; DOI:10.1161/CIRCULATIONAHA.115.016930. Article