Heavy menstrual bleeding in women treated with rivaroxaban and vitamin K antagonists and the risk of recurrent venous thromboembolism.

Anticoagulants increase the risk of heavy menstrual bleeding (HMB). We sought to investigate the incidence, predictors and management of HMB in women on rivaroxaban compared to those on vitamin K antagonists (VKA). We addressed the issue as to whether HMB is associated with VTE recurrences. We performed a single-center prospective study in menstruating women aged 18-55years treated with rivaroxaban or VKA≥3months since the index VTE episode. Seventy six women on rivaroxaban and 45 patients on VKA were included. Patients on rivaroxaban more commonly reported HMB compared with those on VKA (31 [41%] vs. 8 [18%], p=0.009). Women treated with rivaroxaban more frequently needed interventions to reduce menstruation compared with those on VKA (29 [38%] vs. 6 [13%], p=0.004). During the median follow-up time of 13months, there were 8 (11%) recurrent VTE on rivaroxaban and 3 (7%) on VKA (p=0.5). Rivaroxaban treatment predisposed to HMB (odds ratio [OR] 3.2, 95% [confidence interval] CI 1.4-8.2, p=0.007) and the interruption of anticoagulant treatment for 2-3days (OR 3.2, 95% CI 1.1-11.6, p=0.033). HMB during the rivaroxaban treatment predisposed to recurrent VTE (OR 5.3, 95% CI 1.1-33.3, p=0.038). In menstruating women following VTE, rivaroxaban is associated with a two-fold higher risk of HMB compared with VKA. HMB predisposes to recurrent VTE episode, most likely due to the short interruptions of anticoagulation.

Bryk AH ，Piróg M ，Plens K ，Undas A ... -  《-》

Abnormal uterine bleeding in VTE patients treated with rivaroxaban compared to vitamin K antagonists.

Rivaroxaban is a convenient oral anticoagulant for patients with venous thromboembolism (VTE). The impact of rivaroxaban and vitamin K antagonists (VKAs) on abnormal uterine bleeding (AUB) in real life has not been previously explored. We performed a single-center retrospective study on AUB in female VTE patients of reproductive age who were treated with either rivaroxaban or VKAs. Questionnaire results were available for 52 patients in each treatment group. Approximately two thirds of all women reported AUB after initiation of anticoagulant therapy. Patients using rivaroxaban were more likely to experience prolonged (>8days) menstrual bleeding (27 % vs. 8.3%, P=0.017). Rivaroxaban treatment increased the duration of menstrual bleeding from median 5 (IQR 3.5-6.0) days before start of treatment to 6 (IQR 4.1-8.9) days (P<0.001). VKA treatment did not lead to significant prolongation of the menstrual period. Patients on rivaroxaban more frequently reported an unscheduled contact with a physician for AUB than women using VKAs (41% vs. 25%, P=0.096). They also reported increased need for menorrhagia-related medical or surgical intervention (25% vs. 7.7%, P=0.032) and had more adaptations of anticoagulant therapy (15% vs. 1.9%, P=0.031). AUB is frequent after initiation of anticoagulant therapy for acute symptomatic VTE. Compared to VKAs, rivaroxaban was associated with prolonged menstrual bleeding and more medical interventions and adaptation of anticoagulant treatment for AUB. These data can guide proactive discussion with patients starting anticoagulant therapy.

De Crem N ，Peerlinck K ，Vanassche T ，Vanheule K ，Debaveye B ，Middeldorp S ，Verhamme P ，Peetermans M ... -  《-》

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration.

Martinelli I ，Lensing AW ，Middeldorp S ，Levi M ，Beyer-Westendorf J ，van Bellen B ，Bounameaux H ，Brighton TA ，Cohen AT ，Trajanovic M ，Gebel M ，Lam P ，Wells PS ，Prins MH ... -  《-》

Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: a French nationwide propensity-matched cohort study.

The safety and effectiveness of non-vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy. With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched-treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64-1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72-1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64-1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47-1.85) risks were comparable between rivaroxaban and VKA new users. In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

Maura G ，Blotière PO ，Bouillon K ，Billionnet C ，Ricordeau P ，Alla F ，Zureik M ... -  《-》

Comparative safety and effectiveness of rivaroxaban versus VKAs in patients with venous thromboembolism. A Danish nationwide registry-based study.

Sindet-Pedersen C ，Langtved Pallisgaard J ，Staerk L ，Gerds TA ，Fosbøl EL ，Torp-Pedersen C ，Gislason G ，Olesen JB ... -  《-》