Roy* 1, 2, S. Dhanda1, 2, L. Wise1, S. Shakir1, 2

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

Background

Clinical trials and observational studies have reported bleeding risk in patients taking oral anticoagulants. It is valuable to understand the predictors for major bleeding in patients prescribed rivaroxaban in primary care in England.

Objectives

Multivariable logistic regression (MLR) analyses to explore potential risk factors for major bleeding within gastrointestinal (GI), urogenital (UG) and intracranial (IC) sites.

Methods

A case/non-case design was used to study the association between clinical risk factors and major bleeding in a cohort of rivaroxaban patients (N=17546) in a single-arm Modified-Prescription Event Monitoring study identifying patients from dispensed prescriptions in England (2012-2016), followed for 12 months. Clinical risk factors for bleeding and bleeding outcomes were collected from prescribing general practitioners via questionnaires sent at ≥3, and ≥12 months observation. Univariate and multivariable logistic regression analyses were performed to examine the association for each different site. Multivariable analyses models were based on 2 different clinical approaches; Clinical Risk Factors Selection (CS) model and HAS-BLED (HB) model. The CS model included all reported clinical risk factors for bleeding. The HAS-BLED model included the HAS-BLED clinical risk score categories (low, moderate or high risk) and gender. Statistically significant (p<0.05) associations from the MLR models are presented in the results section.

Results

Risk factors for Major GI bleed (n=176)

CS Model: Age 65-74 years vs <65 years: OR=2.4 [95% CI 1.3, 4.6]; Age ≥75years vs <65 years: OR=4.2 [95% CI 2.3, 7.5]; Predisposition to or history of bleeding: OR=4.8 [95% CI 3.1, 7.5] HB Model: Moderate vs low: OR=4.0 [95% CI 2.1, 7.6]; High vs low: OR=8.9 [95% CI 4.0, 19.9] Risk factors for Major UG bleed (n=36) CS Model: Age 65-74 years vs <65 years: OR=0.2 [95% CI 0.1, 0.7]; Females vs males: OR= 2.9 [95% CI 1.4, 6.1]; Malignancy: OR=2.6 [95% CI 1.1, 6.3] HB Model: Females vs males: OR=2.7 [95% CI 1.3, 5.6] Risk factors for Major IC bleed (n=57) CS Model: Age ≥75 years vs <65 years: OR=2.8 [95% CI 1.1, 6.9]; History of cerebrovascular accident/transient ischaemic attack (CVA/TIA) (including haemorrhagic CVA): OR=2.2 [95% CI 1.3, 3.9]; Predisposition to or history of bleeding: OR 2.6 [95% CI 1.0, 6.7] HB Model: Moderate vs low: OR=3.3 [95% CI 1.2, 9.1]; High vs low: OR=9.0 [95% CI 2.5, 31.9]

Conclusion

Use of the case/non-case design to explore risk factors for bleeding in rivaroxaban patients using the CS model identified age ≥65 and history of bleeding or predisposition as statistically significant prognostic factors for major GI bleeds. For major UG bleeds, age group 65-74 years, female gender (which may be related to vaginal bleeding including menorrhagia) and malignancy were statistically significant in the CS model. For major IC bleeds, age ≥75 years, history of CVA/TIA and history of bleeding or predisposition to bleeding were identified as statistically significant risk factors in the CS model. The HB model showed that moderate and high risk scores were statistically significant risk factors for major GI and IC bleeds and gender statistically significant for major UG bleeds. Overall, findings from the CS model and the HB model are in keeping with known clinical risk factors for bleeding.