Award Title: Anticoagulation in advanced Chronic Kidney Disease- Exploring and Guiding Current Prescribing Practice in the UK
Funder: Health Education England

Abstract: Patients with chronic kidney disease (CKD) are at increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Usual treatment for VTE or AF includes anticoagulant therapy. However, they are also at an increased risk of bleeding making the decision to initiate anticoagulation complex. Unlike the general population there is a lack of evidence to support the benefits and define the risks of anticoagulation in patients with advanced CKD. A dearth of guidance or recommendations for anticoagulation in the nephrology field, from acute anticoagulation to long term prevention, is evident. Patients with CKD do not have access to educational materials to support their decision-making process with a class of medicines defined high-risk . The aim of this research is to develop a practice guideline for anticoagulation prescribing in advanced CKD to support patients and clinicians. There will be four workstreams to this study: Workstream 1- The current evidence base will be identified with a systematic review of the literature relating to anticoagulant prescribing practise in advanced CKD. Appropriate databases and grey literature will be searched. This review will form the basis of a questionnaire of UK prescribing practice which will be developed by the research team and Manchester Kidney Patient Research Advisory Group (MKPRAG) and distributed online via both renal and haematology networks. Workstream 2- Identification of the reasons for variation in anticoagulation prescribing protocols will be identified using a purposive sample of professionals from workstream 1. Telephone interviews using 'think out-loud' methodology case vignettes will allow us to investigate the cognitive processes involved in anticoagulation decision-making and factors affecting treatment choice. Identification of primary care prescribing practice and outcomes will be investigated through retrospective analysis of data from FARSITE, a pre-existing database. A preliminary search identified 1207 patients with CKD and AF where investigation of primary effectiveness (ischemic stroke) and primary safety (major bleeding) will be undertaken using a Cox proportional hazards regression with statistician input. Workstream 3- Exploration of CKD patient's views and experiences of anticoagulation will be undertaken using focus groups with a purposive sample of patients. The focus group topics will be designed with MKPRAG and include information needs of patients when making treatment decisions. Focus groups will be audio-recorded with thematic analysis of the transcripts undertaken by the research team and the MKPRAG.Workstream 4- The Delphi method will be used to develop consensus with experts on best anticoagulant practice in the UK. Statements will be prepared by the research team using findings from workstreams 1, 2 and 3. Pre-defined criteria will determine when consensus has been reached with a maximum of three rounds. Appropriate statements from the consensus will be included. The patient co-applicant, MKPRAG and selected focus group members will work to compile the patient section of the guideline using findings from workstream 3. A Renal Association (RA) guide of best practice for anticoagulation in CKD will be formed by the research team, expert reference group and MKPRAG which will be disseminated via conferences, patient networks and haematology forums.

Lay Abstract: Blood thinning medications- known as anticoagulants- are high risk medications because under-dosed patients are at risk of blood clots and over-dosed patients are at risk of bleeding, often with fatal consequences. Patients with chronic kidney disease (CKD) are at higher risk of experiencing both clotting and bleeding episodes than those with normal kidney function. There exists a thin line between the risks (bleeding and clots) and benefits (improved survival) of anticoagulation in kidney patients. This makes anticoagulant use in this group of patients more complex. There is strong evidence that patients with CKD have an increased risk of atrial fibrillation (a heart rhythm disturbance) which can lead to stroke. However these patients also have an increased risk of bleeding without any anticoagulation compared to those with normal kidney function. Unfortunately there are still large gaps in what is known about the use of blood thinning drugs in this population. This means that treatment decision is highly variable as it is challenging for health professionals when making anticoagulation decisions to decide what might be best for the patient. Discussions with patients are tough as there is not necessarily enough information available to help them to make an informed decision about their treatment options. There is a lack of knowledge regarding CKD patient perspectives on anticoagulant therapy. We don't know what CKD patients are more concerned by- clots or bleeding- this study aims to explore some of these ideas and perspectives. Patients' knowledge of their medication and medical condition can affect treatment outcomes, and this becomes more critical in patients prescribed oral anticoagulants due to the narrow window of safety of this class of medication, and the potentially devastating sequelae of both under and over treatment. This study aims to identify differences in prescribing and reasons for these differences. The study will undertake a nationwide survey of current practice and follow this up with some in-depth interviews with clinical staff. Patients' views will be sought on anticoagulation to help understand patients' concerns and ideas. All of these parts of the study will then be used to help form the basis of a guideline that will be agreed upon with a group of experts in this field and a group of patients. This document should support both clinicians and patients when making difficult decisions around anticoagulant treatment. Patients and the public will be a key part of this work with a patient co-applicant and support from the Manchester Kidney Patient Research Advisory Group. The patient co-applicant has been involved in the design of the study from the beginning and there will be regular input during the study from the Patient Research Advisory Group. As the research progresses the findings will be presented at scientific conferences with written papers for scientific journals. A summary of findings will be distributed in kidney patient magazines. In addition links available from the research teams' expertise will be used to publicise these findings as extensively as possible.

Research Activity Codes: 6.1 PHARMACEUTICALS;7.3 MANAGEMENT AND DECISION MAKING
Health Categories: RENAL AND UROGENITAL