Atrial fibrillation (AF) is a commonly occurring abnormal heartbeat. Patients with AF are at high risk of having strokes. Blood thinners such as direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) are effective for stroke prevention. However, their benefit comes with an increased risk of bleeding. The clinical trials that studied the effects of DOACs in patients with AF excluded patients with liver disease. However, liver disease can increase the risk of stroke as well as the risk of bleeding. In addition, liver disease can affect the pharmacology of DOACs. Thus, the aim of our study is to describe how these drugs are used, their effectiveness for stroke prevention, and their safety with respect to bleeding in patients with both AF and liver disease. To this end, we will first describe the patterns of prescription of DOACs in these patients from 2011 to 2019. Then, we will compare the occurrence of stroke, bleeding, and death between DOACs and VKAs during the same time period. Finally, we will compare the rates of stroke, bleeding, and death between apixaban and rivaroxaban, which are two commonly used DOACs.
Patients with liver disease were systematically excluded from the randomized trials assessing the efficacy and safety of direct oral anticoagulants (DOACs) for stroke prevention in non-valvular atrial fibrillation (NVAF). However, liver disease can modify the pharmacology of DOACs, and it can also increase both the thrombotic and the bleeding risk of NVAF patients, which complicates anticoagulant treatment in this vulnerable population. To date, observational studies assessing the effectiveness and safety of DOACs in NVAF patients with concomitant liver disease have been scarce. Moreover, they had methodological limitations rendering the interpretation of their results difficult. Of note, no studies have compared head-to-head apixaban versus rivaroxaban, the two DOACs most used for stroke prevention in NVAF. Thus, the objective of this study will be to assess the utilisation, effectiveness, and safety of DOACs in NVAF patients with liver disease, while also comparing apixaban versus rivaroxaban in the same population. To this end, we will first describe the utilisation of DOACs in NVAF patients with liver disease between 2011 (the year DOACs were approved for stroke prevention in NVAF in the United Kingdom) and 2019 by characterising the groups of patients who initiate DOACs versus the therapeutic alternative vitamin K antagonists (VKAs), characterising the groups of patients who switch from VKAs to DOACs versus remaining on VKAs, and assessing long-term treatment persistence of DOACs versus VKAs. Then, we will assess the association between use of DOACs vs use of VKAs and risk of ischaemic stroke, major bleeding, and all-cause mortality in NVAF patients with liver disease. We will also the association between use of apixaban vs use of rivaroxaban and risk of these outcomes. For confounding control, we will use inverse probability of treatment weighting-based propensity scores. Finally, we will estimate the net clinical benefit of DOACs vs VKAs (and apixaban vs rivaroxaban).
Ischaemic stroke, major bleeding, all-cause mortality, net clinical benefit.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Antonios Douros - Corresponding Applicant - McGill University
Christel Renoux - Collaborator - McGill University
Giada Sebastiani - Collaborator - McGill University
Kristian Filion - Collaborator - McGill University
Robert Platt - Collaborator - McGill University
Ying Cui - Collaborator - Sir Mortimer B Davis Jewish General Hospital
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation