Keith A A Fox

Keith A A Fox
The University of Edinburgh | UoE · Centre for Cardiovascular Science

MB ChB, FRCP, F Med Sci

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1,168
Publications
184,610
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Publications

Publications (1,168)
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
Full-text available
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...
Article
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...
Article
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...
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Full-text available
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...
Article
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...
Article
Full-text available
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
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Full-text available
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...
Article
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...
Article
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...
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Full-text available
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...
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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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
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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...
Article
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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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
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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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
Background/Introduction The PEGASUS-TIMI 54 trial showed that prolonged treatment with ticagrelor reduces the cumulative occurrence of ischemic adverse events. CLARIFY is the biggest real life registry on chronic coronary syndrome. Purpose - To evaluate the percentage of patients eligible for long-term ticagrelor therapy in the CLARIFY registry. –...
Article
Introduction Atrial fibrillation (AF) remains a common cause of stroke and anticoagulation (AC) treatment reduces the risk of stroke. Reasons for patients with AF not receiving anticoagulation are generally attributed to the clinician decision, however in reality a proportion of patients refuse anticoagulation. The aim of our study was to investiga...
Article
Background In patients with coronary or peripheral artery disease, intensified antithrombotic therapy with aspirin plus low dose rivaroxaban reduced cardiovascular outcomes compared with aspirin alone. Polypharmacy and multimorbidity are frequent in patients with vascular disease and are often perceived as barriers to more intensive pharmacotherapy...
Article
Background Non-Vitamin K Antagonists (NOAC) are replacing vitamin K Antagonists (VKA) as first line oral anticoagulant therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF). Discontinuation of OAC might put patients at increased risk. It was anticipated that patients who were on NOAC would discontinue OAC less. Purpose We compare...
Article
Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial demonstrated that the combination therapy of rivaroxaban and aspirin reduced major adverse cardiovascular events (MACE) compared to aspirin alone in patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD). Purpose W...
Article
Importance: Patients with symptomatic lower extremity peripheral artery disease (LE-PAD) experience an increased risk of major vascular events. There is limited information on what clinical features of symptomatic LE-PAD prognosticate major vascular events and whether patients at high risk have a greater absolute benefit from low-dose rivaroxaban...
Article
Background and purpose: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascul...
Preprint
Full-text available
Objectives: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the efficacy and safety of this approach is uncertain. We investigated whether an early-rule out pathway is safe and effective for the management of patients with suspected acute coronary syndrome. Design: A stepped-wedge cluster randomise...
Article
Aims: Prediction models for outcomes in atrial fibrillation (AF) are used to guide treatment. While regression models have been the analytic standard for prediction modelling, machine learning (ML) has been promoted as a potentially superior methodology. We compared the performance of ML and regression models in predicting outcomes in AF patients....
Article
Background Longitudinal bleeding risk scores have been validated in patients treated with dual antiplatelet therapy (DAPT) following percutaneous coronary intervention. How these scores apply to the population of patients with acute coronary syndrome (ACS) treated without revascularization remains unknown. The objective was to evaluate and compare...
Article
Full-text available
Background: Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of pati...
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Full-text available
Anticoagulant plasma concentrations and patient characteristics might affect the benefit–risk balance of therapy. The study objective was to assess the impact of model-predicted rivaroxaban exposure and patient characteristics on outcomes in patients receiving rivaroxaban for venous thromboembolism (VTE) prophylaxis (VTE-P) after hip/knee replaceme...
Article
Full-text available
Rivaroxaban exposure and patient characteristics may affect the rivaroxaban benefit–risk balance. This study aimed to quantify associations between model-predicted rivaroxaban exposure and patient characteristics and efficacy and safety outcomes in patients with non-valvular atrial fibrillation (NVAF), using data from the phase 3 ROCKET AF trial (N...
Article
Full-text available
Anticoagulant plasma concentrations and patient characteristics might affect the benefit–risk balance of therapy. This study assessed the impact of model-predicted rivaroxaban exposure and patient characteristics on outcomes in patients receiving rivaroxaban for venous thromboembolism treatment (VTE-T) using data from the phase 3 EINSTEIN–DVT and E...
Article
Full-text available
Aims: The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain. Methods and results: In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n = 48 282...
Article
Background: Rivaroxaban 2.5mg twice daily plus aspirin 100mg reduced the risk of cardiovascular events as compared to aspirin monotherapy in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial but increased the risk of major bleedings. Analysis of net clinical benefit (NCB) is of key clinical relevance and repres...
Article
Aims: The COMPASS trial demonstrated that the combination of rivaroxaban 2.5mg twice-daily and aspirin 100mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD) by 24% during a mean follow-up of 23 months. We...
Article
Full-text available
Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE...
Article
Introduction High incidence of bleeding events remains a key risk for patients taking anticoagulants, especially those in need of long-term combination therapy with antiplatelet agents. As a consequence, patients may not receive clinically indicated combination antithrombotic therapy. Here, we report on VE-1902, a member of a novel class of precisi...