Risk of Recurrent Bleeding Events in Nonvalvular Atrial Fibrillation Treated with Vitamin K Antagonists: A Clinical Practice Research Datalink Study.

David Evans,Steven Lister,Cormac Sammon,Min You,Alex Bird,Ian Menown,Raza Alikhan,Cinira Lefevre

doi:10.1055/s-0039-1698413

Abstract

Background There is little evidence on how the occurrence of a bleed in individuals on vitamin K antagonists (VKAs) impacts the risk of subsequent bleeds, and thromboembolic and ischemic events. Such information would help to inform treatment decisions following bleeds. Objective To estimate the impact of bleeding events on the risk of subsequent bleeds, venous thromboembolism (VTE), stroke, and myocardial infarction (MI) among patients initiating VKA treatment for new-onset nonvalvular atrial fibrillation (NVAF). Methods We conducted an observational cohort study using a linked Clinical Practice Research Datalink—Hospital Episode Statistics dataset. Among a cohort of individuals with NVAF, the risk of clinically relevant bleeding, VTE, stroke, and MI was compared between the period prior to the first bleed and the periods following each subsequent bleed. The rate and cost of general practitioner (GP) consultations, prescriptions, and hospitalizations were also compared across these periods. Results The risk of clinically relevant bleeding events was observed to be elevated at least twofold in all periods following the first bleeding event. The risk of VTE, stroke, and MI was not found to differ according to the number of clinically relevant bleeding events. The rate and cost of GP consultations, GP prescriptions, and hospitalizations were increased in all periods relative to the period prior to the first bleed. Conclusions The doubling in the risk of bleeding following the first bleed, taken alongside the stable risk of MI, VTE, and stroke, suggests that the risk–benefit balance for VKA treatment should be reconsidered following the first clinically relevant bleed.

Highlights

The risk of venous thromboembolism (VTE), stroke, and myocardial infarction (MI) was not found to differ according to the number of clinically relevant bleeding events
Atrial fibrillation (AF) is associated with an increased risk of arterial thromboembolism and ischemic stroke, and the use of oral anticoagulant (OAC) treatments is recommended for patients with AF and elevated CHA2DS2-VASc risk scores.[7,8]
Study Population The study population consisted of all individuals in the Clinical Practice Research Datalink (CPRD)-HES linked database with a vitamin K antagonists (VKAs) prescription recorded between the January 1, 2003 and the December 31, 2013 who met the following criteria: AF diagnosis recorded prior to their first VKA prescription, no evidence of valvular AF, at least 18 years old at first VKA prescription, at least 12 months of follow-up prior to the first VKA prescription, no evidence of prior Non-VKA OACs (NOACs) of VKA use, and registered with a practice meeting CPRD quality criteria for at least 12 months before the first VKA prescription, with records that met CPRD quality criteria (►Supplementary Fig. S1)

Summary

Introduction

AF is associated with an increased risk of arterial thromboembolism and ischemic stroke, and the use of oral anticoagulant (OAC) treatments is recommended for patients with AF and elevated CHA2DS2-VASc (stroke) risk scores.[7,8] Conventionally, vitamin K antagonists (VKAs) have been used for anticoagulation for stroke prevention in AF patients as well as the treatment and prevention of recurrent venous thromboembolism (VTE). There is little evidence on how the occurrence of a bleed in individuals on vitamin K antagonists (VKAs) impacts the risk of subsequent bleeds, and thromboembolic and ischemic events. Such information would help to inform treatment decisions following bleeds

Methods

Results

Conclusion