Early Risks of Death, Stroke/Systemic Embolism, and Major Bleeding in Patients With Newly Diagnosed Atrial Fibrillation.

BACKGROUND: Atrial fibrillation is associated with increased risks of death, stroke/systemic embolism, and bleeding (incurred by antithrombotic therapy), which may occur early after diagnosis. METHODS: We assessed the risk of early events (death, stroke/systemic embolism, and major bleeding) over 12 months and their relation to the time after diagnosis of atrial fibrillation in 52 014 patients prospectively enrolled in the GARFIELD-AF registry (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) between March 2010 and August 2016. RESULTS: Over 12 months, 2140 patients died (mortality rate, 4.3; 95% CI, 4.2-4.5 per 100 person-years), of whom 288 (13.5%) died in the first month (6.8; 95% CI, 6.1-7.6). Over 12 months, 657 patients had a stroke/systemic embolism (1.3; 95% CI, 1.2-1.4) and 411 had a major bleeding (0.8; 95% CI, 0.8-0.9). During the first month, the rates (per 100 person-years) of stroke/systemic embolism and major bleed were 2.3 (95% CI, 1.9-2.8) and 1.5 (95% CI, 1.2-1.9), respectively. The elevated 1-month mortality rate was mostly attributable to cardiovascular mortality (3.5; 95% CI, 3.0-4.1), in particular, heart failure, sudden death, and acute coronary syndromes (1.0 [95% CI, 0.8-1.4], 0.6 [95% CI, 0.4-0.8], and 0.5 [95% CI, 0.3-0.8], respectively). Age, heart failure, prior stroke, history of cirrhosis, vascular disease, moderate-to-severe kidney disease, diabetes mellitus, and living in North or Latin America were independent predictors of a higher risk of early death, whereas anticoagulation and living in Europe or Asia were independent predictors of a lower risk of early death. A predictive model developed for the 1-month risk of death had a C-statistic of 0.81 (95% CI, 0.78-0.83). CONCLUSIONS: The increased hazard of early events, in particular, cardiovascular mortality, in newly diagnosed atrial fibrillation points to the importance of comprehensive care for such patients and should alert clinicians to detect warning signs of possible early mortality. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01090362.

Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals.

BACKGROUND: The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata. METHODS AND FINDINGS: A systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%-1.82%) and 0.41% (95% CI, 0.31%-0.53%) for <65-year-olds. New AF detection rate increased progressively with age from 0.34% (<60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (<60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60-64 years; and 1,089 for <60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples. CONCLUSIONS: People with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and >70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations.

Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Factors associated with work productivity among people with COPD: Birmingham COPD Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are more likely to take time off work (absenteeism) and report poor performance at work (presenteeism) compared to those without COPD. Little is known about the modifiable factors associated with these work productivity outcomes. AIM: To assess the factors associated with work productivity among COPD patients. METHODS: Cross-sectional analysis of baseline data from a subsample (those in paid employment) of the Birmingham COPD Cohort study. Absenteeism was defined by self-report over the previous 12 months. Presenteeism was assessed using the Stanford Presenteeism Scale. Logistic regression analysis was used to assess the effects of sociodemographic, clinical and occupational characteristics on work productivity. RESULTS: Among 348 included participants, increasing dyspnoea was the only factor associated with both absenteeism and presenteeism (p for trend<0.01). Additionally, increasing history of occupational exposure to vapours, gases, dusts or fumes (VGDF) was independently associated with presenteeism (p for trend<0.01). CONCLUSIONS: This is the first study to identify important factors associated with poor work productivity among patients with COPD. Future studies should evaluate interventions aimed at managing breathlessness and reducing occupational exposures to VGDF on work productivity among patients with COPD.

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists.

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably.

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

BACKGROUND: Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. METHODS/DESIGN: In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach. DISCUSSION: This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. TRIAL REGISTRATION: Current controlled trials ISRCTN14930255.

An international longitudinal registry of patients with atrial fibrillation at risk of stroke (GARFIELD): the UK protocol.

BACKGROUND: Atrial fibrillation (AF) is an independent risk factor for stroke and a significant predictor of mortality. Evidence-based guidelines for stroke prevention in AF recommend antithrombotic therapy corresponding to the risk of stroke. In practice, many patients with AF do not receive the appropriate antithrombotic therapy and are left either unprotected or inadequately protected against stroke. The purpose of the Global Anticoagulant Registry in the FIELD (GARFIELD) is to determine the real-life management and outcomes of patients newly diagnosed with non-valvular AF. METHODS/DESIGN: GARFIELD is an observational, international registry of newly diagnosed AF patients with at least one additional investigator-defined risk factor for stroke. The aim is to enrol 55,000 patients at more than 1000 centres in 50 countries worldwide. Enrolment will take place in five independent, sequential, prospective cohorts; the first cohort includes a retrospective validation cohort. Each cohort will be followed up for 2 years. The UK stands to be a significant contributor to GARFIELD, aiming to enrol 4,582 patients, and reflecting the care environment in which patients with AF are managed. The UK protocol will also focus on better understanding the validity of the two main stroke risk scores (CHADS2 and CHA2DS2VASC) and the HAS-BLED bleeding risk score, in the context of a diverse patient population. DISCUSSION: The GARFIELD registry will describe how therapeutic strategies, patient care, and clinical outcomes evolve over time. This study will provide UK-specific comprehensive data that will allow a range of evaluations both at a national level and in relation to global data and contribute to a better understanding of AF management in the UK. TRIAL REGISTRATION: ClinicalTrial.gov: NCT01090362.

ICSH guidance for INR and D-dimer testing using point of care testing in primary care.

This guideline has been written on behalf of the International Council for Standardisation in Haematology (ICSH) and focuses on two point of care haematology tests used within primary care, namely International Normalised Ratio (INR) and D-dimer. Primary care covers out of hospital settings and can include General Practice (GP), Pharmacy and other non-hospital settings (although these guidelines would also be applicable to hospital out-patient settings). The recommendations are based on published data in peer reviewed literature and expert opinion; they should supplement regional requirements, regulations or standards.

Optimising prediction of mortality, stroke, and major bleeding for patients with atrial fibrillation: validation of the GARFIELD-AF tool in UK primary care electronic records.

BACKGROUND: The GARFIELD-AF tool is a novel risk tool that simultaneously assesses the risk of all-cause mortality, stroke or systemic embolism, and major bleeding in patients with atrial fibrillation (AF). AIM: To validate the GARFIELD-AF tool using UK primary care electronic records. DESIGN AND SETTING: A retrospective cohort study using the Clinical Practice Research Datalink (CPRD) linked with Hospital Episode Statistics data and Office for National Statistics mortality data. METHOD: Discrimination was evaluated using the area under the curve (AUC) and calibration was evaluated using calibration-in-the-large regression and calibration plots. RESULTS: A total of 486 818 patients aged ≥18 years with incident diagnosis of non-valvular AF between 2 January 1998 and 31 July 2020 were included; 50.6% (n = 246 425/486 818) received anticoagulation at diagnosis The GARFIELD- AF models outperformed the CHA2DS2VASc and HAS-BLED scores in discrimination ability of death, stroke, and major bleeding at all the time points. The AUC for events at 1 year for the 2017 models were: death 0.747 (95% confidence interval [CI] = 0.744 to 0.751) versus 0.635 (95% CI = 0.631 to 0.639) for CHA2DS2VASc; stroke 0.666 (95% CI = 0.663 to 0.669) versus 0.625 (95% CI = 0.622 to 0.628) for CHA2DS2VASc; and major bleeding 0.602 (95% CI = 0.598 to 0.606) versus 0.558 (95% CI = 0.554 to 0.562) for HAS- BLED. Calibration between predicted and Kaplan- Meier observed events was inadequate with the GARFIELD-AF models. CONCLUSION: The GARFIELD-AF models were superior to the CHA2DS2VASc score for discriminating stroke and death and superior to the HAS-BLED score for discriminating major bleeding. The models consistently underpredicted the level of risk, suggesting that a recalibration is needed to optimise its use in the UK population.

International longitudinal registry of patients with atrial fibrillation at risk of stroke: Global Anticoagulant Registry in the FIELD (GARFIELD).

BACKGROUND: Atrial fibrillation (AF) is associated with high rates of morbidity and mortality. Patients with AF carry a fivefold increased risk of stroke and the risk of death from AF-related stroke is doubled. Current management is often inadequate, leaving patients at risk for a potentially fatal or disabling event. The purpose of the GARFIELD registry is to evaluate the management and outcomes of patients with newly diagnosed non-valvular AF at risk for stroke. DESIGN: The GARFIELD registry is an observational, multicenter, prospective study of patients with newly diagnosed AF and one or more additional risk factors for stroke. The aim is to enroll 55,000 patients at >1,000 centers in 50 countries. Enrollment will take place in five independent, sequential, prospective cohorts. An additional retrospective validation cohort of 5,000 patients with established AF and at least one additional risk factor for stroke will be conducted in parallel with cohort one. The study started in December 2009, with a planned recruitment period of 4 years and a minimum of 2-year follow-up for each patient. SUMMARY: The GARFIELD registry will provide valuable insights into the clinical management and related outcomes of AF patients throughout many regions of the world and across the spectrum of healthcare systems. By capturing data from unselected patients treated in everyday practice, the registry has the potential to identify best practices as well as deficiencies in available treatment options for specific patient populations and to describe how therapeutic strategies, patient care, and outcomes will evolve over time.

GARFIELD-AF risk score for mortality, stroke, and bleeding within 2 years in patients with atrial fibrillation.

AIMS: To determine whether the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) integrated risk tool predicts mortality, non-haemorrhagic stroke/systemic embolism, and major bleeding for up to 2 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 and clinical characteristics, choice of treatment, and lifestyle factors. A Cox proportional hazards model was identified for each outcome by least absolute shrinkage and selection operator methods. Indices were evaluated in comparison with CHA2DS2-VASc and HAS-BLED risk predictors. Models were validated internally and externally in ORBIT-AF and Danish nationwide registries. Among the 52 080 patients enrolled in GARFIELD-AF, 52 032 had follow-up data. The GARFIELD-AF risk tool outperformed CHA2DS2-VASc for all-cause mortality in all cohorts. The GARFIELD-AF risk score was superior to CHA2DS2-VASc for non-haemorrhagic stroke, and it outperformed HAS-BLED for major bleeding in internal validation and in the Danish AF cohort. In very low- to low-risk patients [CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)], the GARFIELD-AF risk score offered strong discriminatory value for all the endpoints when compared to CHA2DS2-VASc and HAS-BLED. The GARFIELD-AF tool also included the effect of oral anticoagulation (OAC) therapy, thus allowing clinicians to compare the expected outcome of different anticoagulant treatment decisions [i.e. no OAC, non-vitamin K antagonist (VKA) oral anticoagulants, or VKAs]. CONCLUSIONS: The GARFIELD-AF risk tool outperformed CHA2DS2-VASc at predicting death and non-haemorrhagic stroke, and it outperformed HAS-BLED for major bleeding in overall as well as in very low- to low-risk group patients with AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF: NCT01090362, ORBIT-AF I: NCT01165710; ORBIT-AF II: NCT01701817.

Cluster randomised controlled trial of screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the pilot study for the SAFER trial.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures. METHODS AND ANALYSIS: SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective. ETHICS AND DISSEMINATION: The London-Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

Does self-management of oral anticoagulation therapy improve quality of life and anxiety?

BACKGROUND: Research related to service requirements for anticoagulation management has focussed on clinical and health economic outcomes and paid little attention to the impact of treatment and service delivery on patients' quality of life. This was the first large UK study to evaluate the effect of patient self-management (PSM) of oral anticoagulation on treatment-related quality of life (TRQoL) and anxiety in comparison with routine care (RC) and to explore the effect of level of therapeutic control on TRQoL and anxiety across and within each model of care. METHODS: A quantitative survey, set in primary care in the West Midlands. The subjects were 517 randomized controlled trial participants, 242 receiving PSM and 275 RC. Postal questionnaires at baseline and 12 months comprised the State Trait Anxiety Inventory and a treatment-specific measure of positive (satisfaction and self-efficacy) and negative aspects (daily hassles, strained social network and psychological distress) of TRQoL. Change in anxiety and TRQoL scores were compared between PSM and RC. Subgroup analysis was based upon level of therapeutic control (high, medium and low). RESULTS: Overall, 83% (n = 202) PSM and 55% (n = 161) RC patients contributed data. Anxiety scores were similar in both groups. PSM demonstrated greater improvement in self-efficacy than RC across the study period. A statistically significant between-group difference (PSM versus RC) in the self-efficacy also existed in subgroups with medium and high levels of therapeutic control. CONCLUSIONS: PSM is not associated with increased anxiety and has a positive effect upon some aspects of TRQoL compared to RC.

Cardioversion in patients with newly diagnosed non-valvular atrial fibrillation: observational study using prospectively collected registry data.

OBJECTIVE: To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN: Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING: 1317 participating sites in 35 countries. PARTICIPANTS: 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES: Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS: 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. CONCLUSION: In this large dataset of patients with recent onset non-valvular atrial fibrillation, a small proportion were treated with cardioversion. Direct current cardioversion was performed twice as often as pharmacological cardioversion, and there appeared to be no major difference in outcome events for these two cardioversion modalities. For the overall cardioversion group, after adjustments for confounders, a significantly lower risk of mortality was found in patients who received early cardioversion compared with those who did not receive early cardioversion. STUDY REGISTRATION: ClinicalTrials.gov NCT01090362.

Risks associated with discontinuation of oral anticoagulation in newly diagnosed patients with atrial fibrillation: Results from the GARFIELD-AF Registry.

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 the Global Anticoagulant Registry in the Field-Atrial Fibrillation study who discontinued OAC. METHODS: Oral anticoagulation discontinuation was defined as cessation of treatment for ≥7 consecutive days. Adjusted outcome risks were assessed in 23 882 patients with 511 days of median follow-up after discontinuation. RESULTS: Patients who discontinued (n = 3114, 13.0%) had a higher risk (hazard ratio [95% CI]) of all-cause death (1.62 [1.25-2.09]), stroke/systemic embolism (SE) (2.21 [1.42-3.44]) and myocardial infarction (MI) (1.85 [1.09-3.13]) than patients who did not, whether OAC was restarted or not. This higher risk of outcomes after discontinuation was similar for patients treated with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) (p for interactions range = 0.145-0.778). Bleeding history (1.43 [1.14-1.80]), paroxysmal vs. persistent AF (1.15 [1.02-1.29]), emergency room care setting vs. office (1.37 [1.18-1.59]), major, clinically relevant nonmajor, and minor bleeding (10.02 [7.19-13.98], 2.70 [2.24-3.25] and 1.90 [1.61-2.23]), stroke/SE (4.09 [2.55-6.56]), MI (2.74 [1.69-4.43]), and left atrial appendage procedures (4.99 [1.82-13.70]) were predictors of discontinuation. Age (0.84 [0.81-0.88], per 10-year increase), history of stroke/transient ischemic attack (0.81 [0.71-0.93]), diabetes (0.88 [0.80-0.97]), weeks from AF onset to treatment (0.96 [0.93-0.99] per week), and permanent vs. persistent AF (0.73 [0.63-0.86]) were predictors of lower discontinuation rates. CONCLUSIONS: In GARFIELD-AF, the rate of discontinuation was 13.0%. Discontinuation for ≥7 consecutive days was associated with significantly higher all-cause mortality, stroke/SE, and MI risk. Caution should be exerted when considering any OAC discontinuation beyond 7 days.

Comparative effectiveness of oral anticoagulants in everyday practice.

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 mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category (CHA2DS2-VASc) score ≥2 (excluding gender) in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation registry were analysed using an improved method of propensity weighting, overlap weights and Cox proportional hazards models. RESULTS: All-cause mortality, non-haemorrhagic stroke/systemic embolism (SE) and major bleeding over 2 years were compared in 25 551 patients, 7162 (28.0%) not treated with oral anticoagulant (OAC) and 18 389 (72.0%) treated with OAC (FXaI (41.8%), DTI (11.4%) and VKA (46.8%)). OAC treatment compared with no OAC treatment was associated with decreased risk of all-cause mortality (HR 0.82 (95% CI 0.74 to 0.91)) and non-haemorrhagic stroke/SE (HR 0.71 (95% CI 0.57 to 0.88)) but increased risk of major bleeding (HR 1.46 (95% CI 1.15 to 1.86)). Non-vitamin K antagonist oral anticoagulant (NOAC) use compared with no OAC treatment was associated with lower risks of all-cause mortality and non-haemorrhagic stroke/SE (HR 0.67 (95% CI 0.59 to 0.77)) and 0.65 (95% CI 0.50 to 0.86)) respectively, with no increase in major bleeding (HR 1.10 (95% CI 0.82 to 1.47)). NOAC use compared with VKA use was associated with lower risk of all-cause mortality and major bleeding (rates/100 patient-years 3.6 (95% CI 3.3 to 3.9) vs 4.8 (95% CI 4.5 to 5.2) and 1.0 (95% CI 0.9 to 1.1) vs 1.4 (95% CI 1.2 to 1.6); HR 0.79 (95% CI 0.70 to 0.89) and 0.77 (95% CI 0.61 to 0.98) respectively), with similar risk of non-haemorrhagic stroke/SE (rates/100 patient-years 0.8 (95% CI 0.7 to 0.9) versus 1.0 (95% CI 0.8 to 1.1); HR 0.96 (95% CI 0.73 to 1.25). CONCLUSION: Important benefits in terms of mortality and major bleeding were observed with NOAC versus VKA with no difference among NOAC subtypes. TRIAL REGISTRATION NUMBER: NCT01090362.

GARFIELD-AF: a worldwide prospective registry of patients with atrial fibrillation at risk of stroke.

The Global Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) examined real-world practice in a total of 57,149 (5069 retrospective, 52,080 prospective) patients with newly diagnosed AF at risk of stroke/systemic embolism, enrolled at over 1000 centers in 35 countries. It aimed to capture data on AF burden, patients' clinical profile, patterns of clinical practice and antithrombotic management, focusing on stroke/systemic embolism prevention, uptake of new oral anticoagulants, impact on death and bleeding. GARFIELD-AF set new standards for quality of data collection and analysis. A total of 36 peer-reviewed articles were already published and 73 abstracts presented at international congresses, covering treatment strategies, geographical variations in baseline risk and therapies, adverse outcomes and common comorbidities such as heart failure. A risk prediction tool as well as innovative observational studies and artificial intelligence methodologies are currently being developed by GARFIELD-AF researchers. Clinical Trial Registration: NCT01090362 (ClinicalTrials.gov).

Point-of-care testing in haemostasis.

Point-of-care testing (POCT) in haematology has seen a significant increase in both the spectrum of tests available and the number of tests performed annually. POCT is frequently undertaken with the belief that this will reduce the turnaround time for results and so improve patient care. The most obvious example of POCT in haemostasis is the out-of-hospital monitoring of the International Normalized Ratio in patients receiving a vitamin K antagonist, such as warfarin. Other areas include the use of the Activated Clotting Time to monitor anticoagulation for patients on cardio-pulmonary bypass, platelet function testing to identify patients with apparent aspirin or clopidogrel resistance and thrombelastography to guide blood product replacement during cardiac and hepatic surgery. In contrast to laboratory testing, POCT is frequently undertaken by untrained or semi-trained individuals and in many cases is not subject to the same strict quality control programmes that exist in the central laboratory. Although external quality assessment programmes do exist for some POCT assays these are still relatively few. The use of POCT in haematology, particularly in the field of haemostasis, is likely to expand and it is important that systems are in place to ensure that the generated results are accurate and precise.

Impact of COPD case finding on clinical care: a prospective analysis of the TargetCOPD trial.

OBJECTIVES: To investigate the impact of chronic obstructive pulmonary disease (COPD) case finding on clinical care. DESIGN: We conducted a prospective observational analysis of data from a pragmatic cluster randomised controlled trial in primary care in the West Midlands, UK (TargetCOPD). This compared alternative methods of COPD case finding against usual care. Data were extracted from electronic healthcare records and self-reported questionnaires for a subset of patients with newly diagnosed COPD. SETTING: 50 general practices that participated in the TargetCOPD trial. PARTICIPANTS: Patients aged 40-79 years newly identified with COPD by targeted case finding or by usual care, from 10 August 2012 to 22 June 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was addition to a COPD register by the end of the trial. The secondary outcome was a clinical care score, derived from the sum of clinical assessments and relevant interventions. Associations between participant characteristics and the primary and secondary outcomes were assessed using multilevel regression. RESULTS: 857 patients identified with COPD by case finding and 764 by usual care were included. Only 21.2% of case-found patients had been added to a COPD register, compared with 92.7% of those diagnosed by usual care. The odds of being added were greater in smokers (adjusted OR 8.68, 95% CI 2.53 to 29.8), and in those with lower percentage of predicted forced expiratory volume in 1 s (adjusted OR 0.96 per percentage rise, 95% CI 0.95 to 0.98). Patients who had been added to a COPD register had a significantly higher clinical care score (mean difference 5.06, 95% CI 4.36 to 5.75). CONCLUSIONS: Only one in five case-found patients had been registered with COPD. Patients added to a COPD register received significantly higher levels of appropriate clinical care. TRIAL REGISTRATION NUMBER: ISRCTN14930255; Post-results.