Sandeep Dhanda1,2, Miranda Davies1,2, Debabrata Roy1,2, Lesley Wise1, Saad Shakir1,2

Affiliations: 1 Drug Safety Research Unit, 2 University of Portsmouth

Background

Clinical trials and observational studies have reported bleeding risk in patients taking rivaroxaban. A PASS was carried out as part of the Risk Management Plan to monitor the safety and use of rivaroxaban using real-world primary care data in England.

Objectives

To estimate the risk of Major and CRNM bleeding in patients prescribed rivaroxaban for Stroke prevention in non-valvular AF (SPAF) and for the prevention and/or treatment of Deep Vein Thrombosis and/or Pulmonary Embolism DVT/PE in primary care.

Methods

Patients identified from dispensed prescriptions in England (2012-2016). Detailed questionnaires sent to general practitioners (GPs) at ≥3 and ≥12 months of observation collected information on risk factors for bleeding (HAS-BLED) and bleeding outcomes. Summary descriptive statistics and 12-month risk estimates were calculated.

Results

Cohort = 17546 patients: 10225 patients with AF (58.3% of cohort, median age 78 years [IQR 70-84], 5253 (51.4%) male); 5959 patients with DVT/PE (34.0 % of cohort, median age 66 years [IQR 50-78]; 3197 (53.6%) female). In both groups, the median HAS-BLED score was 1 (IQR 1-2, 0-1, respectively) reflecting a low risk of major bleeding.

AF group: Risk Major + CRNM bleeding 8.3% ([95% CI 7.8, 8.9]; n=825). Risk Major bleed 2.4% ([95% CI 2.1, 2.7]; n=239), CRNM bleeding 6.0% ([95% CI 5.5, 6.4]; n=592). Major bleeding further stratified by site: gastrointestinal (GI) (1.2%; n=117), urogenital (UG) (0.1%; n=13), intracranial (IC) (0.4%; n=42), all other critical organ (excluding IC) (0.3%; n=26) and all non-critical organ sites (0.4%; n=44).

DVT/PE group: Risk Major + CRNM bleeding 4.2% ([95% CI 3.7, 4.7]; n=240). Risk Major bleed 1.4% ([95% CI 1.1, 1.7]; n=82), CRNM bleeding 2.8% ([95% CI 2.4, 3.3]; n=162). Major bleeding further stratified by site: GI (0.7%; n=38), UG (0.3%; n=18), IC (0.2%; n=12), all other critical organ (excluding IC) (0.1%; n=4) and all non-critical organ sites (0.2%; n=10).

Conclusions

For the primary outcome of major bleeding, the estimates of risk in the AF and DVT/PE rivaroxaban user populations were overall low and consistent with those estimated from clinical trial data. Differences in methodologies and analysed study populations prevent meaningful comparisons with other studies. This study design has unique strengths, including the collection of timely, granular data directly from prescribing GPs, however selective reporting of outcomes and selection bias might be present, and should be considered when interpreting results.