Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight

Abstract

Objectives To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non‐major bleeding were compared between patients with bodyweight <60 kg, 60‐120 kg, and >120 kg. Methods Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013‐8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. Results Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3‐ and 6‐month incidence of major bleeding compared to the bodyweight 60‐120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60‐120kg group (P = .01). Conclusions Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

Efficacy, Safety, and Exposure of Apixaban in Patients with High Body Weight or Obesity and Venous Thromboembolism: Insights from AMPLIFY

“…Another study in 366 patients with a BMI ≥ 40 kg/m 2 prescribed an anticoagulant for venous thromboembolism (apixaban, n = 47; rivaroxaban, n = 152; warfarin, n = 167) found the incidences of recurrent VTE and major bleeding to be similar between each NOAC and warfarin [ 21 ]. An analysis of the Mayo Clinic VTE Registry consisting of 2577 patients with VTE receiving anticoagulant treatment (apixaban, n = 772; rivaroxaban, n = 502) found similar rates of recurrent VTE and major bleeding between apixaban-treated and rivaroxaban-treated patients across body weight groups (< 60, 60 to 120, and > 120 kg) [ 22 ]. Observational data comparing rivaroxaban with warfarin are available from a propensity score-matched analysis using pooled data from two US claims databases.…”

Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism: Use in Patients with Advanced Renal Impairment, Obesity, or Other Weight-Related Special Populations

“…Another study found recurrent VTE and major bleeding rates that were reduced by more than one-half in obese patients receiving a DOAC compared with a low-molecularweight heparin (LMWH) or warfarin (►Table 6). 84 Again, these results may be clinically meaningful, but only 8.5% of the patients in this study weighed greater than 120 kg. One study attempted to compare rivaroxaban to apixaban and found a rate of recurrent VTE of 6.4% in those receiving rivaroxaban and 0% in patient receiving apixaban (p ¼ 0.49).…”

“…In a prospective observational study, patients weighing less than 60 kg receiving apixaban or rivaroxaban for the treatment of VTE (n ¼ 90) had one-half the rate of recurrent VTE at 3 months compared with patients receiving a DOAC in the reference weight group (n ¼ 1,076; 1.5 vs. 3.2%; p ¼ 0.43), but a doubling in the rate of major bleeding (6.1 vs. 2.7%; p ¼ 0.15). 84 These same trends were also demonstrated with the use of a LMWH and VKA. Use of apixaban or rivaroxaban in these patients with low body weight had a nonsignificant 70% reduction in recurrent VTE (1.5 vs. 5.3%; p ¼ 0.25), and a nonsignificant 44% reduction in major bleeding (6.1 vs. 10.9%; p ¼ 0.32) compared with the use of a LMWH and VKA (n ¼ 71).…”

“…There have been several observational studies that have evaluated the efficacy and safety of DOACs in patients with VTE and obesity (►Table 6). [83][84][85][86][87][88][89][90][91] As previously mentioned, observational studies have several limitations. These studies also have mixed objectives, with some studies primarily comparing outcomes in obese versus nonobese patients, and others comparing DOACs versus warfarin in obese patients.…”

“…79,80 Although the phase 3 VTE data are consistent in patients with obesity, the observational data are limited and often combined with data with rivaroxaban. 39,84,85,90 Other Weight-Related Special Populations…”