Rhythm versus rate control in patients with newly diagnosed atrial fibrillation - Observations from the GARFIELD-AF registry.

Background: Investigate real-world outcomes of early rhythm versus rate control in patients with recent onset atrial fibrillation. Methods: The Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) is an international multi-centre, non-interventional prospective registry of newly diagnosed (≤6 weeks' duration) atrial fibrillation patients at risk for stroke. Patients were stratified according to treatment initiated at baseline (≤48 days post enrolment), and outcome risks evaluated by overlap propensity weighted Cox proportional-hazards models. Results: Of 45,382 non-permanent atrial fibrillation patients, 23,858 (52.6 %) received rhythm control and 21,524 (47.4 %) rate control. Rhythm-controlled patients had lower median age (68.0 [Q1;Q3: 60.0;76.0] versus 73.0 [65.0;79.0]), fewer histories of stroke/transient ischemic attack/systemic embolism (9.4 % versus 13.0 %), and lower expected probabilities of death (median GARFIELD-AF death score 4.0 [2.3;7.5] versus 5.1 [2.8;9.2]). The two groups had the same median CHA2DS2-VASc scores (3.0 [2.0;4.0]) and similar proportions of anticoagulated patients (rhythm control: 66.0 %, rate control: 65.5 %). The propensity-score-weighted hazard ratios of rhythm vs rate control (reference) were 0.85 (95 % CI: 0.79-0.92, p-value < 0.0001) for all-cause mortality, 0.84 (0.72-0.97, p-value 0.020) for non-haemorrhagic stroke/systemic embolism and 0.90 (0.78-1.04, p-value 0.164) for major bleeding. Conclusion: Rhythm control strategy was initiated in about half of the patients with newly diagnosed non-valvular non-permanent atrial fibrillation. After balancing confounders, significantly lower risks of all-cause mortality and non-haemorrhagic stroke were observed in patients who received early rhythm control.

Outcomes of Oral Anticoagulation in Atrial Fibrillation Patients With or Without Comorbid Vascular Disease: Insights From the GARFIELD-AF Registry.

BACKGROUND: Many patients with atrial fibrillation suffer from comorbid vascular disease. The comparative efficacy and safety of different types of oral anticoagulation (OAC) in this patient group have not been widely studied. METHODS: Adults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed for 24 months. Associations of vascular disease with clinical outcomes were analyzed using adjusted hazard ratios (HR) obtained via Cox proportional-hazard modeling. Outcomes of OAC vs no OAC, and of non-vitamin K antagonist OAC (NOAC) vs vitamin K antagonist (VKA) treatment, were compared by overlap propensity-weighted Cox proportional-hazard models. RESULTS: Of 51,574 atrial fibrillation patients, 25.9% had vascular disease. Among eligible atrial fibrillation patients, those with vascular disease received OAC less frequently than those without (63% vs 73%). Over 2-year follow-up, patients with vascular disease showed a higher risk of all-cause mortality (HR 1.30; 95% confidence interval [CI], 1.16-1.47) and cardiovascular mortality (HR 1.59; 95% CI, 1.28-1.97). OAC was associated with a significant decrease in all-cause mortality and non-hemorrhagic stroke, and increased risk of major bleeding in non-vascular disease. In vascular disease, similar but non-significant trends existed for stroke and major bleeding. A significantly lower risk of all-cause mortality (HR 0.74; 95% CI, 0.61-0.90) and major bleeding (HR 0.45; 95% CI, 0.29-0.70) was observed in vascular disease patients treated with NOACs, compared with VKAs. CONCLUSIONS: Atrial fibrillation patients with a history of vascular disease have worse long-term outcomes than those without. The association of NOACs vs VKA with clinical outcomes was more evident in atrial fibrillation patients with vascular disease.

Predictors of intracranial hemorrhage in patients with atrial fibrillation treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF registries.

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 modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. RESULTS: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. CONCLUSIONS: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Oral anticoagulation across diabetic subtypes in patients with newly diagnosed atrial fibrillation: A report from the GARFIELD-AF registry.

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 patients with AF, 11 542 DM and 40 468 non-DM, enrolled in the GARFIELD-AF registry. Follow-up was truncated at 2 years after enrolment. Comparative effectiveness of OAC versus no OAC was assessed by DM status using a propensity score overlap weighting scheme and weights were applied to Cox models. RESULTS: Patients with DM [39.3% oral antidiabetic drug (OAD), 13.4% insulin ± OAD, 47.2% on no antidiabetic drug] had higher risk profile, OAC use, and rates of clinical outcomes compared with patients without DM. OAC use was associated in patients without DM and patients with DM with lower risk of all-cause mortality [hazard ratio 0.75 (0.69-0.83), 0.74 (0.64-0.86), respectively] and stroke/systemic embolism (SE) [0.69 (0.58-0.83), 0.70 (0.53-0.93), respectively]. The risk of major bleeding with OAC was similarly increased in patients without DM and those with DM [1.40 (1.14-1.71), 1.37 (0.99-1.89), respectively]. Patients with insulin-requiring DM had a higher risk of all-cause mortality and stroke/SE [1.91 (1.63-2.24)], [1.57 (1.06-2.35), respectively] compared with patients without DM, and experienced significant risk reductions of all-cause mortality and stroke/SE with OAC [0.73 (0.53-0.99); 0.50 (0.26-0.97), respectively]. CONCLUSIONS: In both patients with DM and patients without DM with AF, OAC was associated with lower risk of all-cause mortality and stroke/SE. Patients with insulin-requiring DM derived significant benefit from OAC.

Guideline-directed medical therapies for comorbidities among patients with atrial fibrillation: results from GARFIELD-AF.

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, international registry of patients with recently diagnosed non-valvular AF at risk of stroke (NCT01090362). Methods and results: Guideline-directed medical therapy was defined according to the European Society of Cardiology guidelines. This study explored co-GDMT use in patients enrolled in GARFIELD-AF (March 2013-August 2016) with CHA2DS2-VASc ≥ 2 (excluding sex) and ≥1 of five comorbidities-coronary artery disease, diabetes mellitus, heart failure, hypertension, and peripheral vascular disease (n = 23 165). Association between co-GDMT and outcome events was evaluated with Cox proportional hazards models, with stratification by all possible combinations of the five comorbidities. Most patients (73.8%) received oral anticoagulants (OACs) as recommended; 15.0% received no recommended co-GDMT, 40.4% received some, and 44.5% received all co-GDMT. At 2 years, comprehensive co-GDMT was associated with a lower risk of all-cause mortality [hazard ratio (HR) 0.89 (0.81-0.99)] and non-cardiovascular mortality [HR 0.85 (0.73-0.99)] compared with inadequate/no GDMT, but cardiovascular mortality was not significantly reduced. Treatment with OACs was beneficial for all-cause mortality and non-cardiovascular mortality, irrespective of co-GDMT use; only in patients receiving all co-GDMT was OAC associated with a lower risk of non-haemorrhagic stroke/systemic embolism. Conclusion: In this large prospective, international registry on AF, comprehensive co-GDMT was associated with a lower risk of mortality in patients with AF and CHA2DS2-VASc ≥ 2 (excluding sex); OAC therapy was associated with reduced all-cause mortality and non-cardiovascular mortality, irrespective of co-GDMT use. Clinical Trial Registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Determinants and clinical outcomes of patients who refused anticoagulation: findings from the global GARFIELD-AF registry.

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 patient refusal of anticoagulation and the clinical outcomes in these patients. METHODS: Our study population comprised patients in the Global Anticoagulant Registry in the FIELD (GARFIELD-AF) registry with CHA2DS2-VASc≥2. A logistic regression was developed with predictors of patient anticoagulation refusal identified by least absolute shrinkage and selection operator methodology. Patient demographics, medical and cardiovascular history, lifestyle factors, vital signs (body mass index, pulse, systolic and diastolic blood pressure), type of AF and care setting at diagnosis were considered as potential predictors. We also investigated 2-year outcomes of non-haemorrhagic stroke/systemic embolism (SE), major bleeding and all-cause mortality in patients who refused versus patients who received and patients who did not receive anticoagulation for other reasons. RESULTS: Out of 43 154 AF patients, who were at high risk of stroke, 13 283 (30.8%) did not receive anticoagulation at baseline. The reason for not receiving anticoagulation was unavailable for 38.7% (5146/13 283); of the patients with a known reason for not receiving anticoagulation, 12.5% (1014/8137) refused anticoagulation. Diagnosis in primary care/general practitioner, Asian ethnicity and presence of vascular disease were strongly associated with a higher risk of patient refusal of anticoagulation. Patient refusal of anticoagulation was associated with a higher risk of non-haemorrhagic stroke/SE (adjusted HR (aHR) 1.16 (95% CI 0.77 to 1.76)) but lower all-cause mortality (aHR 0.59 (95% CI 0.43 to 0.80)) compared with patients who received anticoagulation. The GARFIELD-AF mortality score corroborated this result. CONCLUSION: The data suggest patient refusal of anticoagulation is a missed opportunity to prevent AF-related stroke. Further research is required to understand the patient profile and mortality outcome of patients who refuse anticoagulation.

Healthcare Resource Utilization in Patients with Newly Diagnosed Atrial Fibrillation: A Global Analysis from the GARFIELD-AF Registry.

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 2016 in 35 countries. Components of HCRU studied were hospital admissions, outpatient care visits, and diagnostic and interventional procedures occurring during follow-up. AF-related HCRU was reported as the percentage of patients demonstrating at least one event and was quantified as rate-per-patient-per-year (PPPY) over time. A total of 49,574 patients was analyzed, having an overall median follow-up of 719 days. Almost all patients (99.5%) had at least one outpatient care visit, while hospital admissions were the second most frequent medical contact, with similar proportions in North America (37.5%) and Europe (37.2%), and slightly higher in the other GARFIELD-AF countries (42.0%; namely Australia, Egypt, and South Africa). Asia and Latin America showed lower percentages of hospitalizations, outpatient care visits, and diagnostic and interventional procedures. Analyses of GARFIELD-AF highlighted the vast AF-related HCRU, underlying significant geographical differences in the type, quantity, and frequency of AF-related HCRU. These differences were likely attributable to health service availability and differing models of care.

Two-year outcomes of UK patients newly diagnosed with atrial fibrillation: findings from the prospective observational cohort study GARFIELD-AF.

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 prospective observational cohort study in UK primary care. METHOD: In total, 3574 patients aged ≥18 years with a new AF diagnosis were enrolled. A propensity score was applied using an overlap weighting scheme to obtain unbiased estimates of the treatment effect of anticoagulation versus no anticoagulation on the occurrence of death, non-haemorrhagic stroke/systemic embolism, and major bleeding within 2 years of diagnosis. RESULTS: Overall, 65.8% received anticoagulant therapy, 20.8% received an antiplatelet only, and 13.4% received neither. During the study period, the overall incidence rates of all-cause mortality, non-haemorrhagic stroke/systemic embolism, and major bleeding were 4.15 (95% confidence interval [CI] = 3.69 to 4.65), 1.45 (95% CI = 1.19 to 1.77), and 1.21 (95% CI = 0.97 to 1.50) per 100 person-years, respectively. Anticoagulation treatment compared with no anticoagulation treatment was associated with significantly lower all-cause mortality adjusted hazard ratio (aHR) 0.70 (95% CI = 0.53 to 0.93), significantly lower risk of non-haemorrhagic stroke/systemic embolism (aHR 0.39, 95% CI = 0.24 to 0.62), and a non-significant higher risk of major bleeding (aHR 1.31, 95% CI = 0.77 to 2.24). CONCLUSION: The data support a benefit of anticoagulation in reducing stroke and death, without an increased risk of a major bleed in patients with new-onset AF. Anticoagulation treatment in patients at high risk of stroke who are not receiving anticoagulation may further improve outcomes.

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.

The importance of the design of observational studies in comparative effectiveness research: Lessons from the GARFIELD-AF and ORBIT-AF registries.

Randomized controlled trials (RCTs) are considered the gold standard for estimating the effectiveness of a treatment. However, in many instances they are impractical to conduct because of time limitations, cost restrictions, or ethical reasons. As a consequence, non-randomized observational studies have an important role in comparative effectiveness and safety research since they can address issues that would not be possible using conventional RCT methodology. Observational studies can be strategically designed to reduce the risk of potential sources of bias by emulating the design principles of an equivalent but ideal randomized trial - the target trial - that would answer the research question of interest. In this article, we review some of the necessary components of observational studies required for valid causal inference within the framework of target trial emulation, so as to avoid common methodological pitfalls of study design. We discuss the assumptions of consistency, time-zero specification, exchangeability and positivity. To illustrate these concepts in a context where existing knowledge is well-established through clinical trials, we evaluate and compare the treatment effects of vitamin K antagonists (VKA) against no VKA (No VKA) on the treatment of atrial fibrillation from two real-world observational studies, namely the GARFIELD-AF and ORBIT-AF registries. Results are compared with those of published RCTs.

Residual stroke risk despite oral anticoagulation in patients with atrial fibrillation.

Background: Oral anticoagulation (OAC) reduces the risk of thromboembolic events in patients with atrial fibrillation (AF); however, thromboembolism (TE) still can occur despite OAC. Factors associated with residual risk for stroke, systemic embolism, or transient ischemic attack events despite OAC have not been well described. Objective: The purpose of this study was to evaluate the residual risk of thromboembolic events in patients with AF despite OAC. Methods: A total of 18,955 patients were analyzed in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF I and II) using multivariable Cox proportional hazard modeling. Mean age was 72 ± 10.7, and 42% were women. There were 451 outcome events. Results: The risk of TE despite OAC increased with CHA2DS2-VASc score: 0.76 (95% confidence interval [CI] 0.63-0.92) events per 100 patient-years for CHA2DS2-VASc score <4 vs 2.01 (95% CI 1.81-2.24) events per 100-patient years for CHA2DS2-VASc score >4. Factors associated with increased risk were previous stroke or transient ischemic attack (hazard ratio [HR] 2.87; 95% CI 2.30-3.59; P <.001), female sex (HR 1.52; 95% CI 1.24-1.86; P <.001), hypertension (HR 1.50; 95% CI 1.09-2.06; P = .01), and permanent AF (HR 1.47; 95% CI 1.12-1.94; P = .001). When transient ischemic attack was excluded, the results were similar, but permanent AF was no longer significantly associated with thromboembolic events. Conclusion: Patients with AF have a residual risk of TE with increasing CHA2DS2-VASc score despite OAC. Key risk markers include previous stroke/transient ischemic attack, female sex, hypertension, and permanent AF.

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.

Bleeding and related mortality with NOACs and VKAs in newly diagnosed atrial fibrillation: results from the GARFIELD-AF registry.

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 (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation), a worldwide prospective registry. Baseline treatment was vitamin K antagonists (VKAs) with or without antiplatelet (AP) agents (VKA ± AP) (20 151; 39.3%), NOACs ± AP agents (14 103; 27.5%), AP agents only (10 748; 21.0%), or no antithrombotics (6219; 12.1%). One-year follow-up event rates (95% confidence interval [CI]) of minor, clinically relevant nonmajor (CRNM), and major bleedings were 2.29 (2.16-2.43), 1.10 (1.01-1.20), and 1.31 (1.21-1.41) per 100 patient-years, respectively. Bleeding risk was lower with NOACs than VKAs for any bleeding (hazard ratio (HR) [95% CI]), 0.85 [0.73-0.98]) or major bleeding (0.79 [0.60-1.04]). Compared with no bleeding, the risk of death was higher with minor bleeding (adjusted HR [aHR], 1.53 [1.07-2.19]), CRNM bleeding (aHR, 2.59 [1.80-3.73]), and major bleeding (aHR, 8.24 [6.76-10.04]). The all-cause mortality rate was lower with NOACs than with VKAs (aHR, 0.73 [0.62-0.85]). Forty-five percent (114) of all deaths occurred within 30 days, and 40% of these were from intracranial/intraspinal hemorrhage (ICH). The rates of any bleeding and all-cause death were lower with NOACs than with VKAs. Major bleeding was associated with the highest risk of death. CRNM bleeding and minor bleeding were associated with a higher risk of death compared to no bleeding. Death within 30 days after a major bleed was most frequently related to ICH. This trial was registered at www.clinicaltrials.gov as #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).

Outcomes of Cardiac Catheterization in Patients With Atrial Fibrillation on Anticoagulation in Contemporary in Practice: An Analysis of the ORBIT II Registry.

BACKGROUND: Patients with atrial fibrillation on oral anticoagulation (OAC) undergoing cardiac catheterization face risks for embolic and bleeding events, yet information on strategies to mitigate these risks in contemporary practice is lacking. METHODS: We aimed to describe the clinical/procedural characteristics of a contemporary cohort of patients with atrial fibrillation on OAC who underwent cardiac catheterization. Use of bleeding avoidance strategies and bridging therapy were described and outcomes including death, stroke, and major bleeding at 30 days and 1 year were compared by OAC type. RESULTS: Of 13 404 patients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II Registry from 2013 to 2016, 741 underwent cardiac catheterization (139 with percutaneous coronary intervention) in the setting of OAC. The patients' median age was 71, 61.8% were male, white (87.2%), had hypertension (83.7%), hyperlipidemia (72.1%), diabetes mellitus (31.6%), and chronic kidney disease (28.2%); 20.2% received warfarin while 79.8% received direct acting oral anticoagulant. One third of patients underwent radial artery access, and bivalirudin was used in 4.6%. Bridging therapy was used more often in patients on warfarin versus direct acting oral anticoagulant (16.7% versus10.0%). OAC was interrupted in 93.8% of patients. Patients on warfarin versus direct acting oral anticoagulant were equally likely to restart OAC (58.0% versus 60.7%), had similar use of antiplatelet therapy (44.0% versus 41.3%) after catheterization, and had similar rates of myocardial infarction and death at 1 year, but higher rates of major bleeding (43.3 versus 12.9 events/100 patient years) and stroke (4.9 versus 1.9 events/100 patient years). CONCLUSIONS: In a real-world registry of patients with atrial fibrillation undergoing cardiac catheterization, most cases are elective, performed by femoral access, with interruption of OAC. Bleeding avoidance strategies such as radial artery access and bivalirudin were used infrequently and use of bridging therapy was uncommon. Nearly 40% of patients did not restart OAC postprocedure, exposing patients to risk for stroke. Further research is necessary to optimize the management of patients with atrial fibrillation undergoing cardiac catheterization.

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation.

New artificial intelligence prediction model using serial prothrombin time international normalized ratio measurements in atrial fibrillation patients on vitamin K antagonists: GARFIELD-AF.

AIMS: Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from Global Anticoagulant Registry in the Field (GARFIELD)-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of prothrombin time international normalized ratio (PT-INR) within 30 days of enrolment. METHODS AND RESULTS: Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKAs) and had at least three measurements of PT-INR taken over the first 30 days after prescription were analysed. The AI model was constructed with multilayer neural network including long short-term memory and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0-30 after starting treatment and clinical outcomes over days 31-365 in a derivation cohort (cohorts 1-3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/systemic embolism (SE), and death was assessed in a validation cohort (cohorts 4-5; n = 1523). The model's c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively. CONCLUSIONS: Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analysed by computer to help predict adverse clinical outcomes.

Prior stroke and transient ischemic attack as risk factors for subsequent stroke in atrial fibrillation patients: A report from the GARFIELD-AF registry.

BACKGROUND: It is not always possible to verify whether a patient complaining of symptoms consistent with transient ischemic attack has had an actual cerebrovascular event. RESEARCH QUESTION: To characterize the risk of cardiovascular events associated with a history of stroke/transient ischemic attack in patients with atrial fibrillation. STUDY DESIGN AND METHODS: This study investigated the clinical characteristics and outcomes of patients with a history of stroke/transient ischemic attack among 52,014 patients enrolled prospectively in GARFIELD-AF registry. The diagnosis of stroke or transient ischemic attack was not protocol defined but based on physicians' assessment. Patients' one-year risk of death, stroke/systemic embolism, and major bleeding was assessed by multivariable Cox regression. RESULTS: At enrollment, 5617 (10.9%) patients were reported to have a history of stroke or transient ischemic attack. Patients with stroke or transient ischemic attack were older and had a greater burden of diabetes, moderate-to-severe kidney disease, and atherothrombosis and higher median CHA2DS2-VASc and HAS-BLED scores than those without history of stroke or transient ischemic attack. After adjustment, prior stroke/transient ischemic attack was associated with significantly higher risk for all-cause mortality (hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.12-1.42), cardiovascular death (HR, 1.22; 95% CI, 1.01-1.48), non-cardiovascular death (HR, 1.39; 95% CI, 1.15-1.68), and stroke/systemic embolism (HR, 2.17; 95% CI, 1.80-2.63) than patients without history of stroke/transient ischemic attack. In patients with a prior stroke alone higher risk was observed for all-cause mortality (HR, 1.29; 95% CI, 1.11-1.50), non-cardiovascular death (HR, 1.39; 95% CI, 1.10-1.77), and stroke/systemic embolism (HR, 2.29; 95% CI, 1.83-2.86). No significantly elevated risk of adverse events was seen for patients with history of transient ischemic attack alone. INTERPRETATION: A history of prior stroke or transient ischemic attack is a strong independent risk factor for mortality and stroke/systemic embolism. This excess risk is mainly attributed to a history of stroke (with or without transient ischemic attack), whereas history of transient ischemic attack is a weaker predictor. Clinical trial registration: NCT01090362.