Discussion
sudden cardiac arrest, thrombosis, bleeding, death, nephrotic syndrome, venous thromboembolism
SUDDEN CARDIAC ARREST, THROMBOSIS, THROMBOEMBOLIC EVENT, BLEEDING, HYPERCOAGULABILITY, MINOR, NEPHROTIC SYNDROME, EVENTS
Hypercoagulability, the main pathological change in nephrotic syndrome, is possibly caused by reduced anticoagulants (antithrombin III), increased liver procoagulant synthesis (FIB, factor V, and factor VIII), increased platelet activation and aggregability, and decreased fibrinolytic activity in the kidney [The current study was designed as a prospective, multicenter, randomized clinical trial, and it recruited 180 patients with nephrotic syndrome. This study found no thromboembolic events in the three groups, while low doses of indobufen were associated with a effectively reduced risk of minor bleeding events compared with warfarin. Moreover, APTT and PT levels in the warfarin group were higher than those in the low-dose indobufen group. Finally, one death occurred in the warfarin group; the patient died of sudden cardiac arrest between visits 3 and 4. Finally, other nonspecific AEs predominantly occurred in the warfarin group.This study did not observe any thromboembolic events in the three groups, suggesting that indobufen has an antithrombotic effect equivalent to that of warfarin, and it may be superior to warfarin owing to the significantly lower incidence of minor bleeding events. The trends in serum albumin and creatinine levels in the three groups were similar, suggesting that indobufen did not affect the efficacy of immunosuppressants in the treatment of nephrotic syndrome compared with warfarin. Moreover, the mean APTT and PT values were higher than normal (APTT:23–27 s; PT:11–15 s) after treatment with warfarin, suggesting that the warfarin dose was larger than expected, thus potentially increasing the risk of bleeding. Furthermore, D-dimer concentration decreased slightly in all three groups during the 12-week intervention. However, no statistically significant differences were observed among the three groups. Because D-dimer has a relatively high sensitivity in diagnosing thrombosis [To the best of our knowledge, our study is the first to provide evidence corroborating indobufen’s effectiveness and safety in preventing thromboembolic events in patients with nephrotic syndrome. Although no major bleeding occurred in any of the three groups, we recorded a numerically higher rate of clinically relevant minor bleeding (11/60 vs. 4/120) in the warfarin group than in the indobufen group. Moreover, this study found that treatment with warfarin requires frequent surveillance of INR and poses a higher risk of bleeding, whereas indobufen potentially offers a less burdensome treatment.Notwithstanding, this study has certain limitations. The sample size was relatively small and the duration of follow-up was 12 weeks. Considering the median number of days to the first venous thromboembolism in patients with nephrotic syndrome was 272 days [In conclusion, indobufen, an antiplatelet drug with an anticoagulation effect, provided equivalent effects to warfarin in preventing thromboembolic events and was associated with a reduced risk of bleeding events in adult patients with nephrotic syndrome. Therefore, indobufen is recommended for the prevention of thromboembolic events in patients with nephrotic syndrome. Nonetheless, further large-scale, randomized controlled trials should be performed to verify the efficacy and safety of indobufen in patients with nephrotic syndrome.