VTE is common after total hip (THR) or knee (TKR) replacement. Anticoagulants reduce the risk of VTE but result in bleeding, requiring assessment of benefitrisk.
To improve estimates of treatment effects on lowfrequency events, data were pooled from 4 phase 3 clinical trials (RECORD14) of rivaroxaban vs enoxaparin regimens (or enoxaparin/placebo combination in 1 study) for the prevention of deep vein thrombosis and pulmonary embolism after THR and TKR. Studies differed in treatment duration and comparator dose, but pooling was supported by similar study designs, identical endpoints and event ascertainment methods and the same independent, centralblinded adjudication committee. Benefitrisk was assessed by comparing the excess number of outcome events for benefits vs that for harms over the treatment period. Excess number of events was defined as the number of events in a hypothetical population of 10,000 patients treated with enoxaparin minus the number of events in such a population treated with rivaroxaban. A positive value indicates that fewer events occur in patients treated with rivaroxaban. The analysis was undertaken for several clinically comparable pairs of composite benefit and harm outcomes (Table). Pooled MantelHaenszel weighted risk differences were used to compute excess numbers of benefit and harm events, and differences between excess numbers of events were used to evaluate net clinical benefit (NCB). Benefits and risks were weighted equally. An assessment was also performed using all treatmentemergent serious adverse events (SAEs) as reported by investigators.
Rivaroxaban is associated with significantly fewer total VTE, major VTE, and symptomatic VTE/allcause mortality events than enoxaparin, whereas enoxaparin was associated with a smaller number of bleeding events, although only the composite of major + clinically relevant nonmajor bleeding was significantly different. In each comparison, excess number of bleeding events was less than excess number of VTErelated events by a factor of 410. Enoxaparin was associated with an excess of 194 treatmentemergent SAEs compared with rivaroxaban. In all cases, there was a positive NCB for rivaroxaban vs enoxaparin with 95% confidence intervals excluding 0, suggesting that the benefits of rivaroxaban exceed the risks of enoxaparin.
This quantitative benefitrisk approach compares interventions in a clinically relevant population. Using an NCB approach, for a variety of endpoints, benefits consistently exceed harms for rivaroxaban compared to enoxaparin after elective THR/TKR.
Taxonomy of Interventions to Prevent Adverse Events and Readmissions After Hospital Discharge
To cite this abstract:Turpie A, Levitan B, Berlin J, Homering M, DiBattiste P, Friedman R, Berkowitz S, Yuan Z. Quantitative Benefitrisk Assessment of Rivaroxaban for the Prevention of Venous Thromboembolism (Vte). Abstract published at Hospital Medicine 2012, April 1-4, San Diego, Calif. Abstract 97653. Journal of Hospital Medicine. 2012; 7 (suppl 2). https://www.shmabstracts.com/abstract/quantitative-benefitrisk-assessment-of-rivaroxaban-for-the-prevention-of-venous-thromboembolism-vte/. Accessed July 17, 2019.