OC 15.4 - Menstrual bleeding in adolescents taking dabigatran for acute VTE treatment and secondary prevention

Background: Anticoagulation is associated with an increased risk of abnormal menstrual bleeding (AMB). AMB was less frequent with dabigatran etexilate (DE) than warfarin in adult women with venous thromboembolism (VTE), however AMB was not evaluated in adolescents anticoagulated with DE or standard of care (SOC) in pediatric studies.

Aims: Evaluate AMB events in DE- and SOC-treated adolescent females aged 10 to < 18 years for treatment and secondary VTE prophylaxis from the pediatric trial program.

Methods: AMBs were evaluated in adolescents in DIVERSITY (NCT01895777), where patients with confirmed VTE initially treated with heparins were randomized (2:1) to receive up to 3 months of DE or SOC and the secondary VTE prevention trial (NCT02197416), where patients with persistent VTE risk factors were anticoagulated with DE for up to 12 months (no SOC arm existed in this trial).
AMB events and severity were reported by trial investigators and evaluated from adverse event data. All bleeding events (BE) from both trials were adjudicated. All events occurred on treatment and are reported descriptively.

Results: There were 93 and 72 adolescent females in DIVERSITY and the secondary VTE prevention trial, respectively. AMB occurred in 4/65 (6.2%) DE and 4/28 (14.3%) SOC patients in DIVERSITY (Table). Non-menstrual BEs were reported in 13/65 (20.0%) DE and 11/28 (39.3%) SOC patients. No major but one Clinically Relevant Non-Major (CRNM) BE was reported among AMB events in the DE. In the secondary prevention trial, AMB occurred in 9/72 (12.5%) patients treated with DE, with one CRNM BE, and non-menstrual BEs in 20/72 (27.8%) patients with one major bleeding.

Conclusion(s): Despite small numbers, there were fewer AMBs associated with DE treatment than with SOC in DIVERSITY and an overall low AMB rate in the secondary VTE prevention trial across the adolescent female population from 10 to < 18 years.