The characteristics and incidence of gastrointestinal bleeding and ischaemic stroke in patients with atrial fibrillation using low versus standard-dose anticoagulants

Dr Chan, Esther Wai Yin   (Principal Investigator (PI))

Mr Yan Ka Chun   (Co-Investigator)

Professor Wong Ian Chi Kei   (Co-Investigator)

Dr Chui Sze Ling Celine   (Co-Investigator)

Dr Wan Yuk Fai Eric   (Co-Investigator)

14

2020-06-30

2021-08-29

69330

The characteristics and incidence of gastrointestinal bleeding and ischaemic stroke in patients with atrial fibrillation using low versus standard-dose anticoagulants

anticoagulation, bleed, dose, gastroprotective agent, NOAC, stroke

Gastroenterology/Hepatobiliary,Epidemiology

201910159148

Seed Fund for PI Research – Basic Research

2019

Completed

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant mortality and morbidity, with as much as a 5-fold risk of embolic stroke and 1.5-fold increased risk of stroke per decade (1). AF increases the risk of hospitalisation and adverse drug events, contributing significant burden to patients, caregivers, and society. In Hong Kong, the Hospital Authority saw nearly 90,000 patients with AF in 2017, with an approximate increase of 10,000 patients per year. Considering the significant morbidity and mortality associated with AF and the public health implications in Asia and worldwide, research to optimise the current treatment armamentarium are essential. Currently, oral anticoagulants (OACs; warfarin and non-vitamin K antagonists [NOACs]) are the mainstay prevention for cardioembolic stroke and reduction of mortality in patients with AF. Four NOACs are available in Hong Kong: dabigatran etexilate, rivaroxaban, apixaban, and edoxaban. Yet, therapeutic benefits of NOACs come with an increased risk of bleeding, including gastrointestinal bleeding (GIB), especially in Asians who are predisposed to bleeds. Few studies have assessed the protective role of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) against GIB in patients with AF on NOACs. Our previous study revealed a ~50% reduction in GIB risk among 5,041 patients on dabigatran when gastroprotective agents (PPI/H2RA) were prescribed (incidence rate ratio [IRR], 0.52; 95% CI, 0.35-0.77) (2). This work was incorporated into guideline recommendation made in the European Heart Rhythm Association (EHRA) guidelines (2, 3). The guideline authors noted that this work was the first of its kind to examine GIB prevention with NOACs and that more such studies are needed (2). As the volume of NOACs are increasing in recent years, we are now able to conduct comparative analyses between NOACs with a focus on the incidence of GIB and effectiveness of gastroprotective agents in prevention GIB when different doses (low versus standard) of NOACs are used. To date, evidence on preventive measures against GIB in patients taking NOACs remains scant. In particular, how the dose of NOAC used (low vs standard) affect the incidence of GIB and ischaemic stroke in patients taking NOACs has not been fully characterised, especially in Asians. Moreover, since patients on low-dose NOACs potentially have lower GIB risk, it is currently unknown whether concomitant gastroprotective therapy would further reduce GIB and benefit this patient population. Furthermore, it remains unclear whether concomitant gastroprotective therapy would reduce effectiveness of NOACs to prevent ischaemic stroke, due to potential drug-drug interactions between NOACs and gastroprotective agents (4). Addressing these knowledge gaps, an observational study in real-life clinical practice will provide a comprehensive risk-benefit profile to better guide the choice of gastroprotective agents for prevention of GIB in patients with AF taking different doses of NOACs. Specifically, the objectives of this project are as follows: 1. To determine the characteristics and incidence of GIB and ischaemic stroke in patients with AF using low-dose compared to standard-dose NOACs 2. To determine the characteristics and incidence of GIB and ischaemic stroke comparing PPI/H2RA users versus non-users in patients with AF taking low or standard-dose NOACs References: 1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983-8. 2. Chan EW, Lau WC, Leung WK, Mok MT, He Y, Tong TS, Wong IC. Prevention of Dabigatran-Related Gastrointestinal Bleeding With Gastroprotective Agents: A Population-Based Study. Gastroenterology. 2015;149(3):586-95 e3. 3. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbuchel H, Group ESCSD. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330-93. 4. Bolek T, Samos M, Stanciakova L, Ivankova J, Skornova I, Stasko J, Galajda P, Kubisz P, Mokan M. The Impact of Proton Pump Inhibition on Dabigatran Levels in Patients With Atrial Fibrillation. Am J Ther. 2019;26(3):e308-e13