Gastrointestinal bleeding with direct oral anticoagulants in patients with atrial fibrillation and anaemia.

INTRODUCTION: A high risk of gastrointestinal bleeding has been reported with the use of some direct oral anticoagulants (DOACs). This risk may be of particular concern in individuals with associated anaemia. The aim of this study is to investigate potential differences in the risks of gastrointestinal bleeding and stroke among the four available DOACs in patients with atrial fibrillation (AF) and moderate or severe anaemia. MATERIALS AND METHODS: All Danish patients diagnosed with incident AF who had a baseline haemoglobin measurement and subsequently initiated DOAC therapy between 2012 and 2021 were identified through administrative registries. Only patients with moderate or severe anaemia (N = 7269) were included and evaluated regarding the risk of hospitalization for gastrointestinal bleeding and stroke. Standardized absolute 1-year risks of stroke and gastrointestinal bleeding were calculated from multivariable Cox regression analyses. DOACs were compared pairwise RESULTS: Compared with apixaban, both dabigatran and rivaroxaban were associated with a significantly increased risk of gastrointestinal bleeding with standardized 1-year risk ratios of 1.73 (95 % confidence interval [CI], 1.10-2.35) and 1.56 (95 % CI, 1.18-1.93), respectively, while no significant difference was seen in the comparison of apixaban with edoxaban 1.32 (95 % CI, 0.41-2.32). No significant differences in gastrointestinal bleeding were observed with pairwise comparisons of dabigatran, rivaroxaban and edoxaban. Finally, no significant difference in stroke risk among the four DOACs was observed. CONCLUSION: In AF patients with moderate or severe anaemia, apixaban was associated with a significantly lower risk of gastrointestinal bleeding than dabigatran and rivaroxaban. No significant difference in stroke risk was observed across all four available DOACs.

Safety and efficacy of direct oral anticoagulants in patients with anaemia and atrial fibrillation: an observational nationwide Danish cohort study.

AIMS: The aim of this study was to evaluate the risk of stroke and bleeding among patients with atrial fibrillation (AF) treated with direct oral anticoagulants (DOACs) despite anaemia at treatment initiation time. METHODS AND RESULTS: All Danish patients (N = 41 321) diagnosed with incident AF, having a baseline haemoglobin (Hb), and subsequently initiated DOAC therapy between 2012 and 2019 were identified through administrative registry databases. Patients with anaemia were subdivided according to the World Health Organization classification of anaemia and evaluated regarding risk of stroke and composite bleeding endpoint [hospitalization due to urogenital, gastrointestinal (GI), or intracranial bleeding or epistaxis]. Standardized absolute 1-year risks of stroke and composite bleeding endpoint were calculated using multivariable Cox regression analyses. The standardized absolute 1-year risk difference for composite bleeding increased by 0.96% [95% confidence interval (CI) 0.38-1.54] for patients with moderate/severe anaemia compared with patients with no anaemia. This risk was mainly driven by an increase in standardized absolute 1-year risk for serious GI bleeding, which increased by 0.41% (95% CI 0.19-0.63). No significant difference in standardized absolute 1-year bleeding risk was observed among patients with mild anaemia compared with patients with no anaemia 0.36% (95% CI -0.10 to 0.82). No significant difference in standardized absolute 1-year risk of stroke was observed among patients with mild anaemia, -0.16% (95% CI -0.13 to 0.15), and moderate/severe anaemia, -0.47% (95% CI -0.16 to 0.19), compared with patients with no anaemia. CONCLUSION: For AF patients receiving DOACs, moderate/severe anaemia is a risk factor for serious GI bleeding, while stroke risk is the same regardless of whether anaemia was present at baseline or not.

Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. METHODS: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. RESULTS: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023). CONCLUSIONS: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Plasma YKL-40, a new biomarker for atrial fibrillation?

AIMS: The aim of this study was to determine changes in a new potential biomarker plasma YKL-40 in patients with atrial fibrillation (AF) before and after electrical cardioversion (CV). METHODS AND RESULTS: Plasma concentrations of YKL-40 were measured in 56 patients (mean age 65 years, range 34-84) with persistent AF (lasting mean 128 days, range 14-960), in 19 age-matched patients with permanent AF, and in 19 healthy subjects. The patients with persistent AF underwent CV. Plasma YKL-40 was measured prior to CV, and at follow-up after 24 h, 30 and 180 days. Patients with persistent AF had lower plasma YKL-40 than patients with permanent AF [70 microg/L (42-105)] vs. [138 microg/L (48-225)] (P = 0.003), and higher levels than healthy subjects [41 microg/L (29-52)] (P = 0.001). Patients (n = 22) who were still in sinus rhythm (SR) at follow-up 30 days after CV had unchanged plasma YKL-40 compared with baseline levels. The baseline levels of YKL-40 were correlated to the levels of IL-6, but not to high sensitivity C-reactive protein. CONCLUSION: Patients with AF have significantly elevated levels of YKL-40. YKL-40 was not a significant predictor of successful CV to SR. Plasma levels of YKL-40 did not fall after restoration of SR.

Prognostic impact of hs-CRP and IL-6 in patients with persistent atrial fibrillation treated with electrical cardioversion.

OBJECTIVE: The aim of this study was to assess the role of inflammatory processes in the development of atrial fibrillation (AF) and the prognostic impact of inflammatory markers in predicting long-term risk of AF recurrence after electrical cardioversion (CV). METHODS: High-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were measured in 56 patients with persistent AF (lasting mean 128 days (range 14-960), mean age 65 years (34-84)), 19 healthy volunteers and 19 patients with permanent AF. Patients with persistent AF underwent CV. Blood samples were taken prior to CV and after 1, 30 and 180 days. RESULTS: The immediate success rate of CV was 88%, while the total recurrence rate after 180 days was 68%. Patients with permanent AF had significantly higher levels of hs-CRP and IL-6 than patients with persistent AF (p = 0.0011, p<0.001). Patients in sinus rhythm (SR) after 180 days had significantly lower baseline hs-CRP (1.25 mg/L (0.5-2.4) versus 2.0 mg/L (0.9-3.3), p<0.001) and IL-6 (1.96 pg/mL (1.35-2.7) versus 2.75 pg/mL (1.55-3.62), p<0.001) than patients with recurrent AF. Baseline IL-6 was the only independent predictor of recurrent AF (p = 0.04) in a multivariate Cox analysis. Patients in the lowest hs-CRP quartile (<0.8 mg/L) had significantly lower AF recurrence rates after 180 days (50% versus 74% in the other three quartiles combined; p = 0.0069). CONCLUSION: Patients with AF had elevated levels of inflammatory markers. Low hs-CRP and IL-6 prior to CV are associated with a lower risk of AF recurrence after CV.

ANP and BNP in atrial fibrillation before and after cardioversion--and their relationship to cardiac volume and function.

The role of atrial (ANP) and B-type (BNP) natriuretic peptide in atrial fibrillation (AF) is not clear. Our aim was to describe ANP and BNP in AF, and their changes following cardioversion in persistent AF. Furthermore, we wanted to assess the association between ANP and BNP and cardiac volume and function evaluated by magnetic resonance imaging. ANP and BNP decreased significantly following cardioversion. After 180 days of sinus rhythm, ANP and BNP were still significantly elevated. Same results were seen in patients with lone AF. Left and right atrial volumes correlated positively with ANP and BNP. Changes in left atrial volume were predictive of changes in ANP and BNP following cardioversion. AF may cause enduringly elevated ANP and BNP and atrial volume seems to be an important determinant of ANP and BNP in AF.

Atrial and ventricular volume and function evaluated by magnetic resonance imaging in patients with persistent atrial fibrillation before and after cardioversion.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and 25% of those >40 years old will experience AF. Left atrial size and left ventricular function are independently related to cardiovascular morbidity and mortality. Our aim was to evaluate cardiac volume and function using magnetic resonance imaging in patients with persistent AF and to describe the changes after cardioversion (CV). Sixty consecutive patients with persistent AF and 19 healthy volunteers had cardiac volumes evaluated by cinematographic breath-hold magnetic resonance imaging. Patients with AF were evaluated before CV and at 1, 30, and 180 days after CV, if still in sinus rhythm. All atrial and ventricular volumes and left ventricular mass decreased and ejection fractions increased significantly after CV (p <0.0001 for all variables). Atrial and ventricular diastolic volumes increased significantly the day after CV. The atrial diastolic volumes had decreased significantly at 30 days and ventricular volumes at 180 days. The atrial systolic volumes decreased significantly the day after CV, but the ventricular systolic volumes remained constant the day after CV and decreased thereafter. Only the right atrial volumes were normalized 180 days after CV. The same results were found in a subgroup of patients with lone AF. In conclusion, reversal of atrial dimensions and function happened earlier than ventricular reversal after CV in persistent AF. Atrial reversal began immediately and ventricular reversal was not seen before 30 days after CV. Our results suggest that the changes to the left atrium and both ventricles caused by AF could be permanent and that CV of AF may be preferable.

Atrial and ventricular volume and function in persistent and permanent atrial fibrillation, a magnetic resonance imaging study.

Left atrial size is independently related to cardiovascular morbidity and mortality, and atrial fibrillation (AF) is strongly associated with atrial size. Our aims were to report atrial and ventricular dimensions in patients with AF evaluated with magnetic resonance imaging (MRI), and to assess the inter-study reproducibility of the measurements. Nineteen healthy volunteers, 19 patients with permanent AF, and 58 patients with persistent AF had cardiac dimensions evaluated by 6-mm cinematographic breath-hold MRI scans using a 1.5 Tesla Siemens Vision Magnetom scanner with a phased array chest coil. Intraobserver variability and inter-study reproducibility of the cardiac volumes and ejection fractions (EF) gave acceptable Bland-Altman plots, good correlations (R2: 0.80-0.99), and low reproducibility coefficients. The mean atrial volumes were similar in the two groups with AF [systolic vol. index (SVI): 75.9-80.3 mL/m2; diastolic vol. index (DVI): 77.4-82.1 mL/m2] and significantly different from the healthy volunteers (SVI: 30.3 mL/m2; DVI: 62.3 mL/m2; p < 0.0001). Mean left ventricular (LV) volumes and EF were significantly different in permanent AF (SVI: 34.2 mL/m2; DVI: 68.3 mL/m2; EF: 50.8%) compared to persistent AF [SVI: 44.0 mL/m2 (p = 0.02); DVI: 77.2 mL/m2 (p = 0.03); EF: 44.9% (p = 0.02)], and closer to the normal values (SVI: 22.4 mL/m2; DVI: 66.5 mL/m2; EF: 67.0%). MRI is a highly reproducible method for measurement of atrial and ventricular dimensions in healthy volunteers and in patients with AF. Our results suggest that atrial dilatation appears within the first months of AF and stays more or less unchanged thereafter. The LV appears to dilate early as a response to AF, but later seems to adapt.