Keith A A Fox

University of Edinburgh | UoE · Centre for Cardiovascular Science

The Fourth Universal Definition of Myocardial Infarction recommends a classification based on aetiology, in recognition that the underlying pathophysiology of myocardial infarction influences the approach to investigation and treatment. Type 1 myocardial infarction occurs due to atherosclerotic plaque rupture with thrombosis, whereas type 2 myocard...

Background Physiologic changes due to extremes of body weight may affect the efficacy and tolerability of antiplatelet treatment. However, it remains unclear whether the risks and benefits of intensified antiplatelet therapy among patients with diabetes and stable coronary artery disease (CAD) are affected by body mass index (BMI). Purpose To asse...

Background The incidence of major gastrointestinal bleeding (GIB) in patients on low‐dose direct‐acting oral anticoagulants (DOACs) is relatively unknown. Estimates from randomised controlled trials (RCTs) are lacking. Aims To assess GIB incidence and predictors from RCT data of patients on aspirin, low‐dose rivaroxaban, or both. Methods This was...

Background The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)—the landmark trial...

Background Days alive out of hospital (DAOH) is an objective and patient‐centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. Methods and Results ROCKET AF (Rivaroxaban Once Daily Ora...

Background: In the COMPASS trial, the combination of acetylsalicylic acid (ASA) plus 2.5 mg rivaroxaban twice daily (dual-pathway inhibition, DPI) has been shown to be superior to ASA monotherapy for the reduction in ischemic major adverse cardiovascular events (MACEs, i.e., cardiovascular death, stroke, or myocardial infarction). Methods: The inte...

Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization o...

Background Guidelines for patients with atrial fibrillation (AF) at high thromboembolic risk recommend oral anticoagulants (OACs) for preventing stroke and systemic embolism (SE). The reasons for guideline non-adherence are still unclear. Aim The aim is to identify clinical, demographic and non-patient characteristics associated with withholding O...

Background Oral anticoagulation (OAC) is key in preventing stroke in patients with atrial fibrillation (AF). However, patients with AF and dementia pose practical therapeutic challenges, such as compliance and haemorrhagic complications, resulting in possible underuse of cardiovascular (CV) treatment. Purpose The aim of this study is two-fold: a)...

Background Atrial fibrillation (AF) is associated with cardio-embolic stroke. It remains unclear whether AF outcomes are related to the care speciality at AF diagnosis. Purpose To explore associations between the care speciality at AF diagnosis and the risks of clinical outcomes in newly diagnosed AF patients. Methods GARFIELD-AF is an internatio...

Background Clinical use of the GRACE scoring system is recommended across international guidelines to guide early treatment stratification in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Recently, the machine learning-based GRACE 3.0 score was derived from patients with NSTE-ACS undergoing contemporary treatment appro...

Background: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). Hypothesis: An externally validated model improves ICH risk stratification. Methods: Independent factors associated with ICH were identified by Cox proportional hazard...

Aims: This study aims to describe both management and prognosis of patients with diabetes mellitus (DM) and newly diagnosed atrial fibrillation (AF), overall as well as by antidiabetic treatment, and to assess the influence of oral anticoagulation (OAC) on outcomes by DM status. Methods: The study population comprised 52 010 newly diagnosed pati...

Objective To determine the effectiveness of risk stratification using the Global Registry of Acute Coronary Events (GRACE) risk score (GRS) for patients presenting to hospital with suspected non-ST elevation acute coronary syndrome. Design Parallel group cluster randomised controlled trial. Setting Patients presenting with suspected non-ST elevat...

Aims This study aimed to identify relationships in recently diagnosed atrial fibrillation (AF) patients with respect to anticoagulation status, use of guideline-directed medical therapy (GDMT) for comorbid cardiovascular conditions (co-GDMT), and clinical outcomes. The Global Anticoagulant Registry in the FIELD (GARFIELD)-AF is a prospective, inter...

Objective There is a substantial incidence of stroke in patients with atrial fibrillation (AF) not receiving anticoagulation. The reasons for not receiving anticoagulation are generally attributed to clinician’s choice, however, a proportion of AF patients refuse anticoagulation. The aim of our study was to investigate factors associated with patie...

Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute Cardiovascular Care (ACVC) and Euro...

Background: There is uncertainty surrounding the use of direct oral anticoagulants (DOACs) in patients with kidney dysfunction. Methods: Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY [Randomized Evaluation...

The management of atrial fibrillation (AF), the most common sustained arrhythmia, impacts healthcare resource utilization (HCRU). This study aims to estimate global resource use in AF patients, using the GARFIELD-AF registry. A prospective cohort study was conducted to characterize HCRU in AF patients enrolled in sequential cohorts from 2012 to 201...

Importance In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, there was a significant reduction in the adjudicated primary outcome among patients with stable atherosclerotic vascular disease randomized to dual pathway inhibition (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily) vs aspirin monotherap...

Purpose To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy. Methods A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindop...

Background Many patients with atrial fibrillation (AF) have comorbid vascular disease. The effects of oral anticoagulation (OAC) in AF patients with vascular disease, however, have not been widely studied. Purpose To investigate the impact of OAC in AF patients with (Vasc) or without (nVasc) concomitant vascular disease. Methods GARFIELD-AF is th...

Background Atrial fibrillation (AF) is associated with a significant increase in stroke risk. Anticoagulation (AC) guidelines recommend stratification of stroke risk to aid AC choice. However, despite evidence supporting AC, the associated bleeding risk often leads to underdosing or omission of AC. Transition from stratification of stroke and bleed...

Background Various BP characteristics, e.g., systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), as well as heart rate (HR) may affect the risk of both cardiovascular events and bleeding events. However, the exact way in which these characteristics and outcomes are associated among patients with diabetes and stab...

Background The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is a worldwide non-interventional study of stroke prevention in patients with non-valvular AF.Methods and results52,080 patients with newly diagnosed AF were prospectively enrolled from 2010 to 2016. 4121 (7.9%) of these patients were recruited in DACH [Germ...

Risk stratification plays a key role in identifying acute myocardial infarction (AMI) patients at higher risk of mortality. However, current AMI risk scores such as the Global Registry of Acute Coronary Events (GRACE) score were derived from predominantly Caucasian populations and may not be applicable to Asian populations. We previously developed...

Objective While greater body mass index (BMI) is associated with increased risk of developing atrial fibrillation (AF), the impact of BMI on outcomes in newly diagnosed AF is unclear. We examine the influence of BMI on outcomes and whether this is modified by sex and evaluate the effect of non-vitamin K oral anticoagulants (NOACs) in patients with...

Importance: Type 2 myocardial infarction occurs owing to multiple factors associated with myocardial oxygen supply-demand imbalance, which may confer different risks of adverse outcomes. Objective: To evaluate the prevalence and outcomes of different factors associated with oxygen supply-demand imbalance among patients with type 2 myocardial inf...

Background Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood...

Aims It is unknown whether Asian and non-Asian patients with atherosclerotic vascular disease derive similar benefits from long-term antithrombotic therapy. Methods and results In patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in The Cardiovascular Outcomes for People Using Anticoagulation Strat...

Aims To determine the characteristics of patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both, initiating dual pathway inhibition (DPI) using rivaroxaban 2.5 mg twice daily plus aspirin, and to report their clinical outcomes and bleeding rates in clinical practice compared to the COMPASS randomized trial, which prov...

Aims To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily during long term...

Background Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the...

Aim Atrial fibrillation (AF) management guidelines advise using risk tools to optimize AF treatment. This study aims to develop a dynamic and clinically applicable digital device to assess stroke and bleeding risk, and to facilitate outcome improvements in AF patients. The device will provide tailored treatment recommendations according to easily a...

The benefit and utility of high-sensitivity cardiac troponin (hs-cTn) in the diagnosis of myocardial infarction in patients with kidney impairment is unclear. Here, we describe implementation of hs-cTnI testing on the diagnosis, management, and outcomes of myocardial infarction in patients with and without kidney impairment. Consecutive patients wi...

Background: The outcomes of patients newly diagnosed with atrial fibrillation (AF) following the introduction of direct-acting oral anticoagulants are not well known. Aim: To determine the 2-year outcomes of patients newly diagnosed with AF, and the effectiveness of oral anticoagulants in everyday practice. Design and setting: This was a prosp...

Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) in CKD poses a challenge due to the increased bleeding and clotting tendencies, particularly since patients with CKD were underrepresented in rand...

Objective In patients with newly diagnosed atrial fibrillation (AF), do baseline risk factors and stroke prevention strategies account for the geographically diverse outcomes. Design Global Anticoagulant Registry in the FIELD-Atrial Fibrillation is a prospective multinational non-interventional registry of patients with newly diagnosed AF (n=52 01...

Introduction Diabetes mellitus (DM) is one of the most common comorbidities observed in patients with atrial fibrillation (AF). It is associated with increased risks of stroke/SE and death. Purpose To assess the impact of NOAC and VKA on outcomes of newly diagnosed AF in patients with DM and 2-year follow-up. Methods The study population comprise...

Introduction Rivaroxaban is recommended as an option for anticoagulation in patients with nonvalvular atrial fibrillation (AF) with one or more risk factors for stroke. The approved/recommended rivaroxaban dose for stroke prevention in patients with atrial fibrillation (AF) is solely based on renal function: 20 mg once daily (od) for patients with...

Introduction Large phase III trials of non-valvular atrial fibrillation (AF) patients have shown a favourable risk-to-benefit ratio with Non-Vitamin K antagonist oral anticoagulants (NOAC) compared to Vitamin K antagonists (VKA). Although the results of these trials are directly applicable to many AF patients, important subsets of patients were und...

Introduction Non-vitamin-K oral anticoagulants (NOACs) were recommended in preference to oral vitamin K antagonists (VKAs) in the 2020 updated guidelines for stroke prevention in atrial fibrillation (AF), from the European Society of Cardiology (ESC). Rivaroxaban is a NOAC that is approved in many countries worldwide for reducing the risk of stroke...

Introduction Generalisability of patient selection in the landmark trials for the approval of apixaban (ARISTOTLE) and rivaroxaban (ROCKET AF) for use in non-valvular atrial fibrillation (AF) is limited. Although observational data have confirmed the safety and efficacy of these non-vitamin K oral anticoagulants (NOACs) in unselected AF populations...

Introduction There is debate on the extent to which differences in selection criteria and outcome definitions used for ARISTOTLE and ROCKET AF – the trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular atrial fibrillation – influenced their differences in outcomes relative to vitamin K antagonists (VKAs). In absence o...

Background In event‐driven clinical trials, study termination is based on accrual of a target number of primary efficacy events. For noninferiority trials in which superiority is conditionally examined, the ideal cohort in which to track event accrual is unclear. We used data from the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibiti...

Background p38 mitogen activated kinase (MAPK) mediates the response to pro-inflammatory cytokines following myocardial infarction (MI) and is inhibited by losmapimod. Methods LATITUDE-TIMI 60 (ClinicalTrials.gov NCT02145468) randomized patients with MI to losmapimod or placebo for 12 weeks (24 weeks total follow-up). In this pre-specified analysi...

Aims Peripheral artery disease (PAD) patients suffer a high risk of major cardiovascular (CV) events, with athero-thrombo-embolism as the underlying pathophysiologic mechanism. Recently, two large randomized clinical trials evaluated the efficacy and safety of low-dose rivaroxaban twice daily plus aspirin in stable PAD outpatients and those immedia...

Background: The combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily compared with 100 mg aspirin once daily reduces major adverse cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD). Objectives: The aim of this work was to report the effects of the combinati...

Background In patients with coronary or peripheral arterial disease, adding low dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients. Aims To analyze whether the benefits and risks of rivaroxaban plus aspirin varies in patients with comorbidities and receiving multip...

Importance The relative safety and patency of skeletonized vs pedicled internal mammary artery grafts in patients undergoing coronary artery bypass graft (CABG) surgery are unknown. Objective To investigate the association of skeletonized vs pedicled harvesting with internal mammary artery graft patency and clinical outcomes 1 year after CABG surg...

Background Oral anticoagulation (OAC) in atrial fibrillation (AF) reduces the risk of stroke/systemic embolism (SE). The impact of OAC discontinuation is less well documented. Objective Investigate outcomes of patients prospectively enrolled in GARFIELD-AF who discontinued OAC. Methods OAC discontinuation was defined as cessation of treatment for...

Objective: In patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 m...

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that rivaroxaban plus aspirin reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD). We explored whether CHA2DS2-VASc or CHADS2 scores, well-validated to...

Aims: To determine whether the GARFIELD-AF integrated risk tool predicts mortality, non-haemorrhagic stroke/systemic embolism (SE), and major bleeding for up to two years after new onset AF and to assess how this risk tool performs compared with CHA2DS2-VASc and HAS-BLED. Methods and results: Potential predictors of events included demographic a...

Background Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials. Methods We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials...

Background Insulin use may be a better predictor of stroke risk and morbidity and mortality than diabetes in patients with atrial fibrillation. Objectives Determine if the increased risk of stroke observed in patients with AF and diabetes is restricted to those treated with insulin. Methods We analyzed the association between diabetes and treatme...

Background: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early-rule out pathway is safe and effective for patients with suspected acute coronary syndrome. Methods: We performed a stepped-wedge cluster randomized co...

Patients with acute coronary syndromes (ACS), particularly non-ST-segment elevation ACS, represent a spectrum of patients at variable risk of short- and long-term adverse clinical outcomes. Accurate prognostic assessment in this population requires the simultaneous consideration of multiple clinical and laboratory variables which may be under-recog...

Aims: We estimated the 2020 European Society of Cardiology-Acute Cardio Vascular Care (ESC-ACVC) quality indicators (QI) for the management of acute myocardial infarction, from three existing registries to determine the feasibility of assessment, room for improvement, association with outcomes, and suitability for centre benchmarking. Methods and...

In atrial fibrillation (AF), lower risks of death and bleeding with non-vitamin-K oral anticoagulants (NOACs) were reported in meta-analyses of controlled trials, but whether these findings hold true in real-world practice remains uncertain. Risks of bleeding and death were assessed in 52 032 patients with newly diagnosed AF enrolled in GARFIELD-AF...

Objectives This study evaluated the comparative effectiveness of vitamin K antagonists (VKAs), direct thrombin inhibitors (DTIs) and factor Xa inhibitors (FXaI) in patients with atrial fibrillation (AF) at risk of stroke in everyday practice. Methods Data from patients with AF and Congestive heart failure, Hypertension, Age 75 years, Diabetes mell...

Aims Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. H...

Background Direct oral anticoagulants are administered in fixed doses irrespective of body weight, but guidelines recommend against their use in patients with extremes of body weight. Objectives This study determined the effects of dual-pathway inhibition antithrombotic regimen (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg/day) compared with...

Background ROCKET AF demonstrated the efficacy and safety of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). We examined baseline characteristics and outcomes in patients enrolled in Latin America compared with the rest of the world (ROW). Methods ROCKET AF enrol...

Objectives Persistently impaired culprit artery flow (<TIMI 3) during primary percutaneous coronary intervention is a surrogate for failed myocardial perfusion. We evaluated the effects of intracoronary alteplase according to TIMI flow grade immediately preceding drug administration. Methods In T-TIME (trial of low-dose adjunctive alTeplase during...

Introduction Patients with chronic coronary syndrome (CCS) currently have overall a relatively low rate of long-term ischaemic events but some high risk subsets of patient still experience a worse prognosis such as polyarterial disease patients. Cigarette smoking and diabetes mellitus are strongly associated with polyarterial disease and may be ass...

Importance Although international guidelines recommend use of the Global Registries of Acute Coronary Events (GRACE) risk score (GRS) to guide acute coronary syndrome (ACS) treatment decisions, the prospective utility of the GRS in improving care and outcomes is unproven. Objective To assess the effect of routine GRS implementation on guideline-in...

Background Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction and is independently associated with adverse outcomes. Objective To determine whether or not a strategy involving low-dose intracoronary fibrinolytic therapy infused early after coronary reperfusion will reduce microvascular obstruc...

Background The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) evaluated ticagrelor compared to placebo for the prevention of myocardial infarction (MI), stroke and cardiovascular (CV) death in 19 220 patients with type 2 diabetes (T2DM) and stable coronary artery disease (CAD) with no prior myocard...

Background Coronary artery disease (CAD) and peripheral arterial disease (PAD) represent a significant burden in patients with cardiovascular disease (CVD). However, current antithrombotic therapies are inconsistently used because of clinical concerns about selecting patients with optimal benefit versus risk. Purpose We aimed to determine whether...

Introduction Higher body mass index (BMI) is associated with a higher risk of atrial fibrillation (AF). However, previous evidence has suggested an inverse association between BMI and risk of AF outcomes. Purpose To explore the association between BMI and outcomes in those with newly diagnosed AF in the GARFIELD-AF registry. Methods GARFIELD-AF i...

Introduction The GARFIELD-AF registry is a prospective, multicentre, observational study of adults with recently diagnosed non-valvular atrial fibrillation (AF) and at least one risk factor for stroke. In GARFIELD-AF the absolute risk reduction of mortality associated with anticoagulation is far greater than the apparent absolute risk reduction in...