Abstract
This study aimed to explore the validity of the use of the net clinical benefit (NCB), i.e. the sum of major bleeding and thrombotic events, as a potential surrogate for all-cause mortality in clinical trials assessing antithrombotics. Published randomized controlled trials testing anticoagulants in the prevention or treatment of venous thromboembolism (VTE) and non-valvular atrial fibrillation (NVAF) were systematically reviewed. The validity of NCB as a surrogate endpoint was estimated by calculating the strength of correlation of determination (R2) and its 95% confidence interval (CI) between the relative risks of NCB and all-cause mortality. Amongst the 125 trials retrieved, the highest R2trial values were estimated for NVAF (R2trial = 0.41, 95% CI [0.03; 0.48]), and acute VTE (R2trial = 0.30, 95% CI [0.04; 0.84]). Conversely, the NCB did not correlate with all-cause mortality in prevention studies with medical (R2trial = 0.12, 95% CI [0.00; 0.36]), surgical (R2trial = 0.05, 95% CI [0.00; 0.23]), and cancer patients (R2trial = 0.006, 95% CI [0.00; 1.00]). A weak correlation between NCB and all cause-mortality was found in NVAF and acute VTE, whereas no correlation was observed in clinical situations where the mortality rate was low. Consequently, NCB should not be considered a surrogate outcome for all cause-mortality in anticoagulation trials.
Highlights
This study aimed to explore the validity of the use of the net clinical benefit (NCB), i.e. the sum of major bleeding and thrombotic events, as a potential surrogate for all-cause mortality in clinical trials assessing antithrombotics
The present study aimed to explore the validity of the NCB as a potential surrogate for all-cause mortality in trials testing antithrombotics for the prevention and treatment of venous thromboembolism (VTE) and non-valvular atrial fibrillation (NVAF)
27 studies were conducted in the field of NVAF (114,689 patients), 27 focused on acute treatment of VTE (55,216 patients), 25 on thromboprophylaxis in patients hospitalized for medical conditions (69,022 patients), and 38 on major orthopedic and abdominal surgery (70,982 patients)
Summary
This study aimed to explore the validity of the use of the net clinical benefit (NCB), i.e. the sum of major bleeding and thrombotic events, as a potential surrogate for all-cause mortality in clinical trials assessing antithrombotics. Patients hospitalized for medical illness, undergoing surgery, and cancer patients have a higher risk of venous thromboembolism or bleeding events than the general population[2,3,4] As they reduce the risk of death and injury related to thrombotic events, anticoagulants are the cornerstone of the management of these cardiovascular d iseases[5]. To take into account the balance between potential benefits (i.e. reduced risk of thromboembolism) and harm (i.e. increased risk of major bleeding) in randomized trials, the concept of net clinical benefit (NCB), which is the sum of major bleeding and thrombotic events, appeared recently as a potentially relevant outcome in phase III clinical trials evaluating antithrombotics[14] These measurable events lie within the pathophysiological spectrum of NVAF and VTE, allowing the summarization of treatment effects and increasing the number of total events, increasing the study power.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call