Atrial fibrillation (AF) is a heart condition that increases the risk of stroke. To reduce this risk, individuals with AF are prescribed blood-thinning medications called anticoagulants such as warfarin or the more recently approved direct oral anticoagulants (DOACs). DOACs, including dabigatran, rivaroxaban, edoxaban, and apixaban, are preferred nowadays because of their similar efficacy and their greater ease of use. Many individuals with AF can also present with peripheral artery disease (PAD), in which the leg arteries become narrowed or blocked, affecting blood flow to the legs. PAD can lead to amputations and also increases the risk of stroke. Recent research has suggested that rivaroxaban, at lower dose than used in AF, might be particularly helpful for people with PAD. However, people with both PAD and AF were not studied since these patients need higher dose of DOACs.
Therefore, we will compare the safety and effectiveness of rivaroxaban and apixaban, another DOAC, in individuals who have both AF and PAD. We will examine how frequently they experience stroke, leg problems such as amputations, and bleeding events. This information will assist doctors in determining if rivaroxaban is most suitable for these patients. It could also lead to improved treatment recommendations for these leg artery issues and enhance the overall health of individuals coping with these conditions
Although DOACs are at least as effective and safe compared to VKAs in patients with AF and PAD, little is known about whether some DOACs are more effective and safer than others in this population. Besides, recent trials demonstrated lower cardiovascular and limb events with low dose of rivaroxaban in patients with PAD. Thus, we will conduct a population-based cohort study to determine the effectiveness and safety of rivaroxaban vs apixaban in patients with both AF and PAD. This study will be conducted by linking the CPRD, the HES inpatient and ONS mortality databases. We will form a cohort of patients with non-valvular AF (NVAF) and history of PAD, newly treated with rivaroxaban or apixaban between 2013 and 2021. All patients will be followed until one of the outcomes, death, oral anticoagulant discontinuation/switches, end of registration with the general practice, or end of the study period. Primary effectiveness outcomes will be a composite of stroke, transient ischaemic attack, and systemic embolism other than acute limb ischemia (ALI), and a composite outcome of a major limb event (MALE) defined as a major amputation, minor amputation, ALI, revascularization. The primary safety outcome will be major bleeding or death from bleeding. Secondary outcomes will include major cardiac events (MACE), a composite of a hospitalization for myocardial infarction, stroke, or cardiovascular death, and ALI or major amputation. We will use Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals of the outcomes of interest associated with rivaroxaban compared with apixaban. In secondary analyses, we will perform stratified analyses based on patients’ characteristics, stage of PAD and DOAC dosage. We will use a propensity score (PS)-based fine stratification and weighting to control for potential confounding. Several sensitivity analyses will be performed to assess the robustness of our results.
The primary effectiveness outcomes will be:
-a composite of hospitalisation with an incident ischaemic stroke, transient ischaemic attack (TIA), and systemic embolism (SE) other than acute limb ischemia (ALI).
-major limb event (MALE) defined as a hospitalisation for an ALI, major amputation (above the ankle), minor amputation or lower limb revascularization.
The primary safety outcome of interest will be a hospitalisation for bleeding or a related death.
Secondary outcomes will include:
- Major cardiac event (MACE) defined as a composite of hospitalisation for myocardial infarction, stroke, and cardiovascular death.
- A composite of hospitalisation with an incident ALI or major amputation.
ICD-10 codes are listed in Appendix 1. Corresponding procedure codes in HES are listed in Appendix 1.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Antoine Pariente - Collaborator - Inserm U1219 Bordeaux Population Health Research Center - Team AHeaD
Loubna DARI - Collaborator - McGill University
Sarah Beradid - Collaborator - Sir Mortimer B Davis Jewish General Hospital
HES Admitted Patient Care;ONS Death Registration Data