Rivaroxaban slightly better than warfarin for frail patients with VTE
Treatment with rivaroxaban results in less recurrent venous thromboembolism (VTE) in frail patients with VTE, with similar good bleeding outcomes, compared with warfarin, reports a study.
“The relative effectiveness and safety of rivaroxaban compared with warfarin appears maintained in frail VTE patients treated in routine clinical practice,” researchers said.
A total of 58,089 incident VTE patients were identified, among whom 6,869 (1,365 rivaroxaban and 5,504 warfarin users) were classified as frail. [Am J Med 2018;131:933-938.e1]
Compared with warfarin, rivaroxaban reduced the hazard of the composite of recurrent VTE or major bleeding (hazard ratio [HR], 0.75; 95 percent CI, 0.57–0.98) and recurrent VTE alone (HR, 0.65; 0.44–0.97). There was no significant between-group difference in major bleeding (HR, 0.88; 0.61–1.27).
“We observed a 12-percent nonsignificant reduced hazard of major bleeding with rivaroxaban vs warfarin,” researchers said. “Sensitivity analysis based on the ≥0.20 cutoff of the JHCFI (Johns Hopkins Claims-based Frailty Indicator) score still suggested frail patients given rivaroxaban had at least as good thrombotic and bleeding outcomes as patients prescribed warfarin.”
In the past, frailty definitions used in broad patient populations covered age, cognitive impairment, number of prior hospitalizations, decreased mobility, low income, nutritional deficits and social withdrawal. [Maturitas 2017;95:31-35; J Gerontol A Biol Sci Med Sci 2006;61:262-266]
The EINSTEIN trials defined frailty as the presence of age >75 years, creatinine clearance <50 mL/min, and/or body weight <50 kg. [Thromb J 2013;11:21]
“[D]espite the differences in how frailty was defined and the overall proportion of patients classified as frail, the results of our analysis were generally consistent with those stemming from the EINSTEIN data,” researchers said. [Thromb J 2013;11:21]
In the EINSTEIN trial, patients randomized to receive rivaroxaban had significantly less frequent recurrent VTE or major bleeding compared with those assigned to receive vitamin K antagonist therapy (HR, 0.51; 0.34–0.77), with numerical reductions seen for both recurrent VTE (HR, 0.68) and major bleeding (HR, 0.27).
Additionally, there was a significant difference in major bleeding in favour of rivaroxaban vs vitamin K antagonist in frail patients (HR, 0.27; 0.13–0.54), but no such difference was observed in nonfrail patients (HR, 0.80; 0.49–1.29).
“The preceding results suggest rivaroxaban may be preferable in frail patients, and our sensitivity analysis results further support the EINSTEIN trial finding that major bleeding may be less frequent in frail venous thromboembolism patients treated with rivaroxaban,” researchers said.
“Furthermore, our results are also in overall agreement with the subgroup analyses in frail patients treated with apixaban or edoxaban in the respective phase III VTE treatment trials,” they added. [Thromb J 2014;12:21]
The present study identified frail patients who had ≥1 primary hospitalization/emergency department visit diagnosis codes for VTE, received rivaroxaban or warfarin as their first outpatient oral anticoagulant within 30 days of the index event, and had ≥12 months of insurance prior to the index VTE using the US MarketScan claims data from January 2012 to December 2016.
Researchers adjusted the differences in baseline covariates between cohorts using inverse probability of treatment weights based on propensity scores. The composite of recurrent VTE or major bleeding was the primary endpoint.
Researchers also tracked patient claims for up to 12 months after the index VTE or until endpoint occurrence, oral anticoagulant discontinuation/switch, insurance disenrollment, or end of follow-up. HRs with 95 percent CIs were calculated using Cox regression.