A. Evans 1, 2, M. Davies 1, 2, L. Wise1, S. Shakir1, 2*

1Drug Safety Research Unit, Southampton, 2University of Portsmouth, Portsmouth, United Kingdom

Background

The ROSE (Rivaroxaban Observational Safety Evaluation) Specialist Cohort Event Monitoring (SCEM) study was conducted to monitor the safety and use of rivaroxaban for Stroke Prevention in patients (pts) with non-valvular AF (SPAF) and the prevention and/or treatment of Deep Vein Thrombosis and/or Pulmonary Embolism (DVT/PE) in the secondary care setting in England and Wales. The study complements another study conducted in primary care by focusing on the acute phase of treatment.

Objectives

To estimate the incidence of major and clinically-relevant non-major (CRNM) bleeding (ISTH definition) in patients prescribed rivaroxaban for the first time for SPAF and DVT/PE indications.

Methods

Patients were identified through speciality groups (2013-2016), supported by UK Clinical Research Networks. Risk factors for bleeding (HAS-BLED) and bleeding outcomes were collected via detailed questionnaires completed by hospital specialists at baseline and ≥ 12 weeks. Summary descriptive statistics and 12 week incidence risk and rate (per 100 patient years) were calculated.

Results

The cohort consisted of 2542 pts including 965 patients with AF (38.0% of cohort; median age 76 years [IQR 69, 83], 517 [53.6%] male), median HAS-BLED score 2 (IQR 1-3) (moderate risk of major bleeding) and 1532 patients with DVT/PE (60.3% of cohort; median age 63 years [IQR 48, 73], 836 [54.6%] male), median HAS-BLED score 1 (IQR 0-2) (low risk of major bleeding).

AF group: Rate: Major + CRNM bleeding 28.2 (95% CI 21.0, 37.1; n=51), Major Bleed 5.5 (95% CI 2.6-10.1; n=10), CRNM bleeding 22.7 (95% CI 16.3-30.8; n=41).

Major Bleed risk in pre-specified sites: gastrointestinal (GI) (0.2%; n=2), urogenital (UG) (0.2%; n=2), intracranial (IC) (0.2%; n=2) and all other critical organ (excluding IC) (0.1%; n=1).

DVT/PE group: Rate: Major + CRNM bleeding 36.2 (95% CI 29.4, 44.1; n=98), Major Bleed 8.3 (95% CI 5.3, 12.5; n=23), CRNM bleeding 27.6 (95% CI 21.7, 34.6; n=75).

Major Bleed risk in pre-specified sites: GI (0.7%; n=11), UG (0.3%; n=5), IC (0.1%; n=1) and all other critical organ (excluding IC) (0.0%; n=0).

Conclusions

The incidence of major bleeding was low and no new safety concerns were raised. Unique aspects of this study design enabled collection of highly detailed information from cardiologists, faciliating accurate calculation of risk scores and the application of clinical trial outcome definitions, in a real-word setting. Differences in methodology between this and other study designs prevents meaningful comparison.