45 research outputs found

    Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

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    Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

    Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

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    OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

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

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    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

    Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

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    BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

    Risk factors for left atrial thrombus in younger patients (aged &lt; 65 years) with atrial fibrillation or atrial flutter: Data from the multicenter left atrial thrombus on transesophageal echocardiography (LATTEE) registry

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    BACKGROUND: Our aim was to assess the characteristics and to identify predictors of left atrial thrombus (LAT) in patients under age 65 with atrial fibrillation (AF) or atrial flutter (AFl). METHODS: We conducted a subanalysis of a multicenter, prospective, observational study [the LATTEE registry]. Consecutive AF/AFl patients referred for cardioversion or ablation were enrolled. RESULTS: Of the 3,109 patients included in the study, 1,276 were under age 65 (41%). Compared to non-LAT patients, those with LAT (n = 76) had higher CHA(2)DS(2)-VASc score (p < 0.001), more frequently had non-paroxysmal AF/AFl (p < 0.001), heart failure (p < 0.001), history of diabetes mellitus (p = 0.001), transient ischemic attack (p = 0.04), coronary artery disease (p = 0.02), and chronic kidney disease (p < 0.001). The LAT patients were also more often smokers (p = 0.004) and were more frequently treated with vitamin K antagonists (VKAs) (p < 0.001). Transthoracic echocardiography revealed a higher left atrial area (p < 0.001), lower left ventricular ejection fraction (LVEF) (p < 0.001), and lower value of LA appendage emptying volume in LAT than in non-LAT patients (p < 0.001). LVEF (OR 2.95; 95% CI: 1.32–6.59, p = 0.008), non-paroxysmal AF/AFl (OR 7.1; 95% CI: 2.05–24.63, p = 0.002) and treatment with VKAs (OR 4.92; 95% CI: 2.48–9.75, p < 0.001) were identified as independent predictors of LAT in younger patients. CONCLUSIONS: Our study, which focused on younger patients with AF/AFl, indicated substantial clinical and echocardiographic differences between participants with and without LAT. In the AF/AFl patients younger than age 65, the independent predictors of LAT included non-paroxysmal AF/AFl, lower LVEF, and treatment with VKAs

    Risk factors for left atrial thrombus in younger patients (aged < 65 years) with atrial fibrillation or atrial flutter: Data from the multicenter left atrial thrombus on transesophageal echocardiography (LATTEE) registry

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    BackgroundOur aim was to assess the characteristics and to identify predictors of left atrial thrombus (LAT) in patients under age 65 with atrial fibrillation (AF) or atrial flutter (AFl). MethodsWe conducted a subanalysis of a multicenter, prospective, observational study [the LATTEE registry]. Consecutive AF/AFl patients referred for cardioversion or ablation were enrolled. ResultsOf the 3,109 patients included in the study, 1,276 were under age 65 (41%). Compared to non-LAT patients, those with LAT (n = 76) had higher CHA(2)DS(2)-VASc score (p < 0.001), more frequently had non-paroxysmal AF/AFl (p < 0.001), heart failure (p < 0.001), history of diabetes mellitus (p = 0.001), transient ischemic attack (p = 0.04), coronary artery disease (p = 0.02), and chronic kidney disease (p < 0.001). The LAT patients were also more often smokers (p = 0.004) and were more frequently treated with vitamin K antagonists (VKAs) (p < 0.001). Transthoracic echocardiography revealed a higher left atrial area (p < 0.001), lower left ventricular ejection fraction (LVEF) (p < 0.001), and lower value of LA appendage emptying volume in LAT than in non-LAT patients (p < 0.001). LVEF (OR 2.95; 95% CI: 1.32-6.59, p = 0.008), non-paroxysmal AF/AFl (OR 7.1; 95% CI: 2.05-24.63, p = 0.002) and treatment with VKAs (OR 4.92; 95% CI: 2.48-9.75, p < 0.001) were identified as independent predictors of LAT in younger patients. ConclusionsOur study, which focused on younger patients with AF/AFl, indicated substantial clinical and echocardiographic differences between participants with and without LAT. In the AF/AFl patients younger than age 65, the independent predictors of LAT included non-paroxysmal AF/AFl, lower LVEF, and treatment with VKAs

    Increased Body Mass Index and Risk of Left Atrial Thrombus in Nonvalvular Atrial Fibrillation Patients-Data from the Left Atrial Thrombus on Transesophageal Echocardiography (LATTEE) Registry

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    An increased body mass index (BMI) is associated with a higher incidence of atrial fibrillation (AF) and a higher risk of thromboembolic complications in AF patients. The aim of this study was to investigate the effect of BMI on the risk of left atrial thrombi (LATs) in patients with nonvalvular AF/atrial flutter (AFl) (NV AF/AFl). Patients diagnosed with NVAF/AFl (between November 2018 and May 2020) were selected from the multicenter, prospective, observational Left Atrial Thrombus on Transesophageal Echocardiography (LATTEE) registry that included AF/AFl patients referred for cardioversion or ablation followed by transesophageal echocardiography. A total of 2816 AF/AFl patients (63.6% males; mean age 65.8 years; mean BMI 29.8 kg/m(2)) were included in the study. Two hundred and twenty-two of them (7.9%) had LATs. Compared with normal-weight patients, those with BMIs >= 25 kg/m(2) more frequently presented clinical factors potentially provoking LATs, such as non-paroxysmal AF/AFl (p = 0.04), hypertension (p < 0.001), and diabetes (p < 0.001); had higher CHA(2)DS(2) scores (p < 0.001); and had larger LA dimensions (LA diameter and LA area) (p < 0.001 for both parameters). On the other hand, they showed some features negatively related to thromboembolic risk; for example, they were younger (p < 0.001) and were more often male (p = 0.002). In addition, patients with abnormal BMIs were more likely to be smokers (p = 0.006) and to be treated with oral anticoagulants (p = 0.005). Despite these differences in the prevalence of thromboembolic risk factors, the incidence of LATs was not increased in patients with abnormal body weight (overweight and obese compared to normal-weight patients) in this large real-life cohort of AF/AFl patients. This is probably due to the balanced composition regarding the prevalence of positive and negative thromboembolic risk factors

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

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    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\u2013Atrial Fibrillation (GARFIELD-AF). Among 17\ua0168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (\ub1antiplatelet therapy) at enrolment, and of these patients, 5066 with 653 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70\ua0905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56\ub70% vs 49\ub78%; median, 59\ub77% vs 50\ub70%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0\ub7860 [0\ub7852\u20130\ub7867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0\ub7829 [0\ub7821\u20130\ub7837]). The difference between FIR and TTR explained 17\ub74% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably

    Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients

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    BACKGROUND: The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. METHODS: In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated. RESULTS: A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome--2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P=0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P=0.04). CONCLUSIONS: In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.)

    Evolocumab and clinical outcomes in patients with cardiovascular disease

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    peer reviewedBACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. © 2017 Massachusetts Medical Society
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