Effect of early cryoballoon ablation on atrial fibrillation recurrence-A Danish nationwide register study.

INTRODUCTION: Cryoballoon ablation is a safe and efficient rhythm control strategy in atrial fibrillation (AF) patients. The impact of time from diagnosis to ablation is unclear. The aim of this study was to examine the impact of timing of first-time cryoballoon ablation on AF recurrence in a nationwide cohort of AF patients. METHODS AND RESULTS: From nationwide registers, all AF patients ≥18 years of age who underwent first-time AF cryoballoon ablation in Denmark from 2012 to 2018 were included. The AF patients were stratified by ablation timing: Early group (≤1 year after AF diagnosis), intermediate group (1-3 years after AF diagnosis), and late group (≥3 years after AF diagnosis). By adjusted Cox regression models, the effect of timing on AF recurrence was examined. This study included 1064 AF patients with a median age of 63 years. Most patients were male (66%) and had paroxysmal AF (67%). The 1-year risk of AF recurrence increased from 31% in the early group to 41% and 44% in the intermediate and late group. The hazard ratios (95% confidence intervals) were 1.28 (0.95, 1.74) in the intermediate group and 1.42 (1.09, 1.86) in the late group when compared to the early group. Continuous diagnosis-to-ablation time seemed to have the greatest impact on AF recurrence within the first 2 years. CONCLUSION: In AF patients undergoing cryoballoon ablation, late timing of ablation was associated with a significantly higher AF recurrence rate when compared to early timing of ablation. These findings support early cryoballoon ablation to improve the outcomes after ablation.

Understanding the incidence of Atrial Fibrillation and Stroke in Hypertrophic Cardiomyopathy Patients: Insights from Danish nationwide Registries.

BACKGROUND: The treatment of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) can be challenging since AF aggravates symptoms and increases the risk of stroke. Which factors contribute to the development of AF and stroke in HCM remains unknown. PURPOSE: Determine the incidence of AF and stroke in HCM patients and identify risk factors. METHODS: Using Danish National Registers all HCM patients from 2005-2018 were included. The association between HCM, incident AF and stroke was investigated using multivariable Cox proportional-hazard analysis. Cumulative incidences were calculated using the Aalen-Johansen estimator. RESULTS: Among 3,367 patients without prevalent AF, 24% reached the endpoint of incident AF with death as a competing risk. Median follow-up time was 4 years. AF incidence was equal between sexes and increased for patients with ischemic heart disease (HR 1.33, CI[1.08-1.63]), hypertension (HR 1.36, CI[1.14-1.67]) and obstructive HCM (HR 1.27, CI[1.05-1.52]). A total of 7% developed stroke, with no difference detected stratifying for presence of AF. Sub-analysis revealed that when AF was treated with oral anticoagulants (OAC) stroke was less likely (HR 0.4, CI[0.18-0.86], p = 0.02). However, 34% of patients were not receiving adequate anticoagulation following AF diagnosis. CONCLUSION: Obstructive HCM, hypertension and ischemic heart disease was associated with increased risk of AF. Prevalent AF alone was not predictive of stroke, however AF patients treated with OAC were significantly less likely to develop stroke, suggesting that this development is driven by the protective effect of OAC. Despite this, 34% of patients did not receive OAC.

Short- and long-term risk of atrial fibrillation recurrence after first time ablation according to body mass index: a nationwide Danish cohort study.

AIMS: Overweight is associated with increased risk of atrial fibrillation (AF), but the impact of overweight and AF recurrence after ablation is less clear. Despite this, an increasing number of AF ablations are carried out in overweight patients. We investigated the impact of body mass index (BMI) on AF recurrence rates after ablation. METHODS AND RESULTS: Through Danish nationwide registers, all patients undergoing first-time AF ablation between 2010 and 2018 were identified. Exposure of interest was BMI. The primary outcome was recurrent AF, defined from either any usage of antiarrhythmic medication, AF hospitalization, cardioversion, or re-ablation. A total of 9188 patients were included. Median age and interquartile range was 64 (60-75) in the normal-weight group and 60 (53-66) in the morbidly obese. There was an increase in comorbidity burden with increasing BMI, including a higher prevalence of heart failure, chronic obstructive pulmonary disease, diabetes, and hypertension. At 1- and 5-year follow ups, recurrence rates of AF increased incrementally by BMI categories. The hazard ratios and 95% confidence intervals of recurrent AF after ablation were 1.15 (1.07-1.23), 1.18 (1.09-1.28), and 1.26 (1.13-1.41) in overweight, obese, and morbidly obese, respectively, compared with normal-weight patients. Procedure duration and X-ray dose exposure also increased with increasing BMI. CONCLUSION: Following AF ablation, recurrence rates of AF increased incrementally with increasing BMI. Therefore, aggressive weight management pre ablation in overweight patients could potentially provide substantial benefits and improve short- and long-term outcomes after ablation.

Gastrointestinal bleeding and the risk of colorectal cancer in anticoagulated patients with atrial fibrillation.

AIMS: Gastrointestinal bleeding (GI-bleeding) is frequent in patients with atrial fibrillation (AF) treated with oral anticoagulation (OAC) therapy. We sought to investigate to what extent lower GI-bleeding represents the unmasking of an occult colorectal cancer. METHODS AND RESULTS: A total of 125 418 Danish AF patients initiating OAC therapy were identified using Danish administrative registers. Non-parametric estimation and semi-parametric absolute risk regression were used to estimate the absolute risks of colorectal cancer in patients with and without lower GI-bleeding. During a maximum of 3 years of follow-up, we identified 2576 patients with lower GI-bleeding of whom 140 patients were subsequently diagnosed with colorectal cancer within the first year of lower GI-bleeding. In all age groups, we observed high risks of colorectal cancer after lower GI-bleeding. The absolute 1-year risk ranged from 3.7% [95% confidence interval (CI) 2.2-6.2] to 8.1% (95% CI 6.1-10.6) in the age groups ≤65 and 76-80 years of age, respectively. When comparing patients with and without lower GI-bleeding, we found increased risk ratios of colorectal cancer across all age groups with a risk ratio of 24.2 (95% CI 14.5-40.4) and 12.3 (95% CI 7.9-19.0) for the youngest and oldest age group of ≤65 and >85 years, respectively. CONCLUSION: In anticoagulated AF patients, lower GI-bleeding conferred high absolute risks of incident colorectal cancer. Lower GI-bleeding should not be dismissed as a benign consequence of OAC therapy but always examined for a potential underlying malignant cause.

Impact of Nationwide COVID-19 Lockdowns on the Implantation Rate of Cardiac Implantable Electronic Devices.

AIM: The COVID-19 pandemic resulted in a significant decrease in the number of hospital admissions for severe emergent cardiovascular diseases during lockdowns worldwide. This study aimed to determine the impact of both the first and the second Danish nationwide lockdown on the implantation rate of cardiac implantable electronic devices (CIEDs). METHODS: We retrospectively analysed the number of CIED implantations performed in Denmark and stratified them into 3-week intervals. RESULTS: The total number of de novo CIED implantations decreased during the first lockdown by 15.5% and during the second by 5.1%. Comparing each 3-week interval using rate ratios, a significant decrease in the daily rates of the total number of de novo and replacement CIEDs (0.82, 95% CI [0.70, 0.96]), de novo CIEDs only (0.82, 95% CI [0.69, 0.98]), and non-acute pacemaker implantations (0.80, 95% CI [0.63, 0.99]) was observed during the first interval of the first lockdown. During the second lockdown (third interval), a significant decrease was seen in the daily rates of de novo CIEDs (0.73, 95% CI [0.55, 0.97]), and of pacemakers in total during both the second (0.78, 95% CI [0.62, 0.97]) and the third (0.60, 95% CI [0.42, 0.85]) intervals. Additionally, the daily rates of acute pacemaker implantation decreased during the second interval (0.47, 95% CI [0.27, 0.79]) and of non-acute implantation during the third interval (0.57, 95% CI [0.38, 0.84]). A significant increase was observed in the number of replacement procedures during the first interval of the second lockdown (1.70, 95% CI [1.04, 2.85]). CONCLUSIONS: Our study found only modest changes in CIED implantations in Denmark during two national lockdowns.

Electrical cardioversion of atrial fibrillation and the risk of brady-arrhythmic events.

BACKGROUND: Electrical cardioversion (ECV) is a common procedure for terminating atrial fibrillation (AF). ECV is associated with brady-arrhythmic events, however, the age-specific risks of clinically significant brady-arrhythmic events are unknown. METHODS: Using Danish nationwide registers, we identified patients with AF at their first non-emergent ECV between 2005 and 2018 and estimated their 30-day risk of brady-arrhythmic events. Moreover, factors associated with increased risks of brady-arrhythmias were identified. Absolute risks were estimated using logistic regression models fitted with natural splines as well as standardization (G-formula). RESULTS: We identified 20,725 eligible patients with a median age of 66 years (IQR 60-72) and most males (73%). The 30-day risks of brady-arrhythmic events after ECV were highly dependent on age with estimated risks ranging from 0.5% (95% CI 0.2-1.7) and 1.2% (95% CI 0.99-1.5) to 2.7% (95% CI 2.1-3.3) and 5.1% (95% CI 2.6-9.7) in patients aged 40, 65, 80, and 90 years, respectively. Factors associated with brady-arrhythmias were generally related to cardiovascular disease (eg, ischemic heart disease, heart failure, valvular AF) or a history of syncope. We found no indications that pre-treatment with anti-arrhythmic drugs conferred increased risks of brady-arrhythmic events (standardized absolute risk difference -0.25% [95% CI -0.67 to 0.17]). CONCLUSIONS: ECV conferred clinically relevant 30-day risks of brady-arrhythmic events, especially in older patients. Anti-arrhythmic drug treatment was not found to increase the risk of brady-arrhythmias. Given the widespread use of ECV, these data should provide insights regarding the potential risks of brady-arrhythmic events.

Protocol for detecting unrecognized sleep apnea in patients with atrial fibrillation by a home-monitoring device: the DAN-APNO study.

BACKGROUND: Determining the presence of modifiable risk factors for atrial fibrillation (AF), such as sleep apnea is of clinical importance due to the potential impact targeting these risk factors can have on the progression and burden of AF. Using new digital-based technology is a promising solution to the underreporting of sleep apnea highlighted by academical societies in recent years. The aim of this study is to report the prevalence and severity of sleep apnea in patients with AF and, secondarily, assess the accuracy and feasibility of a new home-screening device for sleep apnea (NightOwl™ by Ectosense). METHODS: DAN-APNO is a cross-sectional study at the Department of Cardiology, Herlev-Gentofte Hospital recruiting patients with AF referred to anticoagulation initiation aged 18 to 90 years without known sleep apnea. At least 150 patients will be recruited and undergo medical history, clinical evaluation, several sleep-apnea questionnaires, and a sleep-recording evaluation for four nights with sleep apnea home-monitoring device NightOwl™. Additionally, the first 20 participants and participants with moderate-severe sleep apnea by screening are referred to cardio-respiratory monitoring (CRM). This clinical evaluation allows the comparison of standard evaluation method and the NightOwl™. Clinical measures include Apnea-Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), pulse rate, as well as questionaries about sleep apnea assessment and the clinical feasibility of the NightOwl™ device. Main outcomes comprise analysis of the prevalence and severity of sleep apnea, and clinical and demographic predictors of moderate and severe sleep apnea. In addition, correlation analyses for accuracy measures between CRM and NightOwl™ will be conducted along with patient ease-of-use and satisfaction questionnaires. DISCUSSION: This study is limited by selection bias; only patients with atrial fibrillation from anticoagulation clinic is asked to participate, which could limit the generalizability of our results. However, this study aims to test whether a miniaturized simple home-monitoring device for detecting sleep apnea in patients with AF potentially can evaluate sleep apnea more conveniently and easier. Trial Registration The study is registered the 18-02-2021 at clinicaltrials.gov with registration number: NCT04760002.

Oral fluoroquinolones and risk of aortic or mitral regurgitation: a nationwide nested case-control study.

AIMS: Reports have suggested an increased risk of aortic and mitral regurgitation associated with oral fluoroquinolones (FQs) resulting in a safety warning published by the European Medicines Agency (EMA). However, these findings have not yet been replicated. METHODS AND RESULTS: Using Danish administrative registers, we conducted a nested case-control study in a nationwide cohort of individuals between 2005 and 2018. Cases were defined as the first occurrence of aortic or mitral regurgitation. Exposure of interest was the use of oral FQs. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were obtained by fitting time-dependent Cox regression models, with penicillin V as comparator, to assess the association between FQ use and incident valvular regurgitation. We identified 38 370 cases of valvular regurgitation with 1 115 100 matched controls. FQ exposure was not significantly associated with increased rates of aortic or mitral regurgitation (HR 1.02, 95% CI 0.95-1.09) compared with penicillin V users. Investigating the cumulative defined daily doses (cDDD) of FQs yielded similar results with no significant association between increasing FQ use and valvular regurgitation (e.g. HR 1.08, 95% CI 0.95-1.23 for cDDD >10 compared with cDDD 1-5). These results were consistent across several analyses including a cohort of patients with hypertension and using a case definition based on valvular surgical interventions. CONCLUSIONS: In a nationwide nested case-control study, FQs were not significantly associated with increased rates of valvular regurgitation. Our findings do not support a possible causal connection between FQ exposure and incident valvular regurgitation.

New-onset atrial fibrillation: incidence, characteristics, and related events following a national COVID-19 lockdown of 5.6 million people.

AIM: To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown. METHODS AND RESULTS: Using nationwide Danish registries, we included all patients, aged 18-90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020. The main comparison was between patients diagnosed during lockdown (12 March 12-1 April 2020) and patients diagnosed in the corresponding period 1 year previously. We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56-0.78), 0.53 (0.45-0.64), and 0.41 (0.34-0.50)]. There was a 47% drop in total numbers (562 vs. 1053). Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent. During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively. The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93-2.12). CONCLUSIONS: Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed. In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.

Catheter ablation for atrial fibrillation is associated with lower incidence of heart failure and death.

AIMS: Catheter ablation for atrial fibrillation (CAF) improves symptoms, but whether CAF improves outcome is less clear. The purpose of this study was to investigate whether CAF is associated with improved outcome in atrial fibrillation (AF) patients with previous direct current (DC) cardioversion. METHODS AND RESULTS: We performed a nationwide cohort study including all patients who underwent their 1st direct current cardioversion for AF in the period 2003-15 (N = 25 439). End points were all-cause death, cardiovascular death, stroke/thromboembolism, and incident heart failure (HF). Catheter ablation for AF was treated as a time-varying covariate and the association with outcome was assessed using Cox regression. We also constructed a propensity-matched cohort and assessed the association between CAF and outcome. Median follow-up was 5.3 years (inter-quartile range 3.0-8.7 years). A total of 3509 patients (13.8%) underwent CAF during the study period. Following adjustment for age, gender, comorbidities, medications, educational level, household income, and CHA2DS2VASc score, CAF was associated with reduced risks of all-cause death, cardiovascular death, and incident HF [all-cause death: hazard ratio (HR) 0.69, P < 0.001; cardiovascular death: HR 0.68, P = 0.003; incident HF: HR 0.76, P = 0.011]. Catheter ablation for AF was not associated with a reduced risk of stroke/thromboembolism. These results were replicated in a propensity-matched cohort. CONCLUSION: In AF patients with a prior DC cardioversion, CAF was associated with a reduced risk of all-cause and cardiovascular death. This may be due to a reduced risk of HF.

Prehospital continuous ECG is valuable for very early detection of atrial fibrillation in patients with acute stroke.

INTRODUCTION: Early detection of atrial fibrillation (AF) after stroke is essential to achieve timely initiation of appropriate prophylactic treatment. We aimed to assess the diagnostic value of using prehospital continuous ECG (cECG) for AF detection after acute stroke. PATIENTS AND METHODS: In this retrospective cohort study, we included AF naïve ischemic stroke patients of 50 years or older. Medical records and corresponding digital prehospital cECGs were systematically reviewed. The proportion of AF detectable by prehospital cECG, in-hospital 12-lead ECG, telemetry and outpatient cECG was determined. McNemar's chi-squared test was used to compare probability of AF on prehospital cECG vs. in-hospital 12-lead ECG. RESULTS: In 500 included patients, a new onset AF was detectable by prehospital cECG in 27 patients (5.4% [95% CI 3.6-7.8]). In-hospital 12-lead ECG detected AF in 28 of 458 patients (6.1% [95% CI 4.1-8.7). Sixty-two (12.4% [95% CI 9.6-15.6]) were diagnosed with new onset AF by either prehospital cECG, in-hospital 12-lead ECG, in-hospital telemetry or outpatient cECG. Thus, 43.5% of all AF cases were detectable during prehospital transport. The probability of AF did not differ between prehospital cECG and in-hospital 12-lead ECG. Nevertheless, a lack in overlapping diagnoses meant number needed to screening with prehospital cECG was 16 for diagnosing one AF case not detected by in-hospital 12-lead ECG. CONCLUSION: Using prehospital cECG as an addition to very early AF evaluation after acute stroke had diagnostic value and could represent a low cost and easily accessible opportunity for very early AF detection. This may improve post-stroke care and save resources for further unnecessary AF screening. Conducting routine prehospital cECG after acute stroke and ensuring this is available to clinicians is encouraged.

Temporal trends in atrial fibrillation recurrence rates after ablation between 2005 and 2014: a nationwide Danish cohort study.

Aims: During the last decade, ablation has increasingly been used in rhythm control management of patients with atrial fibrillation (AF). Over time, experience and techniques have improved and indications for ablation have expanded. The purpose of this study was to investigate whether the recurrence rate of AF following ablation has improved during last decade. Methods and results: Through Danish nationwide registers, all patients with first-time AF ablation, between 2005 and 2014 in Denmark were identified. Recurrent AF after ablation was identified with 1 year follow-up. A total of 5425 patients undergoing first-time ablation were included. While patient median age increased over time the median AF duration prior to ablation decreased. The rates of recurrent AF decreased from 45% in 2005-2006 to 31% 2013-2014 with the relative risk of recurrent AF almost halved with an odds ratio of 0.57 [95% confidence intervals (95% CI) 0.47-0.68] in 2013-2014 compared with patients undergoing ablation in 2005-2006. Female gender, hypertension, AF duration >2 years, and cardioversion within 1 year prior to ablation were all associated with an increased risk of recurrent AF. Conclusion: One year risk of recurrent AF following first-time ablation has almost halved from 2006 to 2014. Hypertension, female sex, cardioversion 1 year prior to ablation, and AF duration for more than 2 years all increased the associated risk of recurrent AF.

Infective endocarditis and risk of death after cardiac implantable electronic device implantation: a nationwide cohort study.

AIMS: To determine the incidence, risk factors, and mortality of infective endocarditis (IE) following implantation of a first-time, permanent, cardiac implantable electronic device (CIED). METHODS AND RESULTS: From Danish nationwide administrative registers (beginning in 1996), we identified all de-novo permanent pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) together with the occurrence of post-implantation IE-events in the period from 2000-2012. Included were 43 048 first-time PM/ICD recipients. Total follow-up time was 168 343 person-years (PYs). The incidence rate (per 1000 PYs) of IE in PM was 2.1 (95% confidence interval [CI]: 1.7-2.6) for single chamber devices and 6.2 (95% CI: 4.5-8.7) for cardiac resynchronization therapy (CRT); similarly, the rate of IE in ICD was 3.7 (95% CI: 2.9-4.7) in single chamber devices and 6.3 (95% CI: 4.4-9.0) in CRT. In multivariable analysis, increased PM complexity served as independent risk factor for IE {dual chamber PM [hazard ratio (HR) 1.39; 95% CI: 1.07-1.80] and CRT [HR: 1.84; 95% CI: 1.20-2.84]}. During follow-up, generator replacement (HR: 2.79; 95% CI: 1.87-4.17) and lead revision (HR: 4.33; 95% CI: 3.25-5.78) in PMs were associated with increased risk. Corresponding estimates in ICDs were 2.49 (95% CI: 1.28-4.86) and 6.58 (95% CI: 4.49-9.63). Risk of death after IE was significantly increased in PM and ICD with HRs of 1.56 (95% CI: 1.33-1.82) and 2.63 (95% CI: 2.00-3.48), respectively. CONCLUSION: The risk of IE increased with increasing PM complexity. Other important risk factors were subsequent generator replacement and lead revision. IE was associated with an increased risk of mortality in the area of CIED.

Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage and examined the impact of subsequent AT use on the long-term clinical outcome. METHODS: We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were identified and followed up. We estimated the hazard ratio of all-cause death, thromboembolic events, or major bleeding according to use of AT. RESULTS: We identified 6369 patients between 2005 and 2013. Among these patients, 2978 (47%) had indication for AT, and during the follow-up, (median: 2.3 year) 1281 (43%) died, 497 (17%) had a thromboembolic event, and 536 (18%) had major bleeding. Postdischarge use of oral anticoagulation therapy among patients with indication for oral anticoagulation therapy was associated with a significant lower risk of death (adjusted hazard ratio, 0.59; 95% confidence interval, 0.43-0.82) and thromboembolic events (adjusted hazard ratio 0.58; 95% confidence interval, 0.35-0.97) and no increased risk of major bleeding (adjusted hazard ratio 0.65; 95% confidence interval, 0.41-1.02). In contrast, use of platelet inhibitors among patients with indication for platelet inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality and thromboembolic events and no increased risk of major bleeding.

Substantial differences in initiation of oral anticoagulant therapy and clinical outcome among non-valvular atrial fibrillation patients treated in inpatient and outpatient settings.

AIMS: Patients with atrial fibrillation (AF) are encountered and treated in different healthcare settings, which may affect the quality of care. We investigated the use of oral anticoagulant (OAC) therapy and the risk of thrombo-embolism (TE) and bleeding, according to the healthcare setting. METHODS AND RESULTS: Using national Danish registers, we categorized non-valvular AF patients (2002-11) according to the setting of their first-time AF contact: hospitalization (inpatients), ambulatory (outpatients), or emergency department (ED). Event rates and hazard ratios (HRs), calculated using Cox regression analysis, were estimated for outcomes of TE and bleeding. We included 116 051 non-valvular AF patients [mean age 71.9 years (standard deviation 14.1), 51.3% males], of whom 55.2% were inpatients, 41.9% outpatients, and 2.9% ED patients. OAC therapy 180 days after AF diagnosis among patients with a CHADS2 ≥ 2 was 42.1, 63.0, and 32.4%, respectively. Initiation of OAC therapy was only modestly influenced by CHADS2 and HAS-BLED scores, regardless of the healthcare setting. The rate of TE was 4.30 [95% confidence interval (CI) 4.21-4.40] per 100 person-years for inpatients, 2.28 (95% CI 2.22-2.36) for outpatients, and 2.30 (95% CI 2.05-2.59) for ED patients. The adjusted HR of TE, with inpatients as reference, was 0.74 (95% CI 0.71-0.77) for outpatients and 0.89 (95% CI 0.79-1.01) for ED patients. CONCLUSION: In a nationwide cohort of non-valvular AF patients, outpatients were much more likely to receive OAC therapy and had a significantly lower risk of stroke/TE compared with inpatients and ED patients. However, across all settings investigated, OAC therapy was far from optimal.

Familial clustering and subsequent incidence of atrial fibrillation among first-degree relatives in Denmark.

AIMS: Atrial fibrillation (AF) is associated with increased morbidity and mortality. Determination and quantification of familial risk may help identify high-risk patients. METHODS AND RESULTS: Using Danish nationwide registry data (1978-2012), we identified all first-time AF patients (probands) in Denmark. Relatives to these probands were grouped according to proband-relation: offspring from either maternal or paternal proband, and siblings to proband. Age-specific incidence of AF for these three groups of relatives and for the general Danish population was estimated. Using the general population as reference, we calculated adjusted rate ratios (RRs) of AF in the three groups of relatives. We identified 67 310, 103 822, and 11 800 AF probands who were mothers (median age 74 years, IQR 66-81), fathers (70 years, IQR 62-78), and siblings (46 years, IQR 38-52), respectively. Among those, 133 516, 221 774, and 21 448 offspring from a maternal proband, offspring from a paternal proband, and siblings, respectively, were screened for incident AF. This was recorded in 2536 (1.9%), 2906 (1.3%), and 292 (1.4%) relatives, respectively. Compared with the general Danish population, the adjusted RRs for incident AF were 3.37 [95% confidence interval (CI) 3.21-3.53] for offspring from maternal probands, 2.81 (95% CI 2.69-2.93) for offspring from paternal probands, and 5.20 (95% CI 4.61-5.85) for siblings to sibling probands. Subgroup analyses showed increased RRs with younger aged probands. CONCLUSION: Familial AF was associated with an increased RR of AF in first-degree relatives compared with the general Danish population. This suggests that familial AF is a major risk factor for developing AF in relatives.

Oral anticoagulation therapy after radiofrequency ablation of atrial fibrillation and the risk of thromboembolism and serious bleeding: long-term follow-up in nationwide cohort of Denmark.

AIM: To investigate the long-term risk of thromboembolism and serious bleeding associated with oral anticoagulation (OAC) therapy beyond 3 months after radiofrequency ablation (RFA) of atrial fibrillation (AF). METHODS AND RESULTS: Linking Danish administrative registries, 4050 patients undergoing first-time RFA (2000-11) were identified. Risk of thromboembolism and serious bleeding according to OAC therapy were analysed by incidence rates (presented per 100 person-years) and Cox proportional-hazard models. The median age was 59.5 years (interquartile range, IQR: 52.8-65.2); 26.5% were females. During a median follow-up of 3.4 years (IQR: 2.0-5.6), 71 (1.8%) thromboembolism cases were identified, where incidence rates with and without OAC were 0.56 (0.40-0.78)95%CI and 0.64 (0.46-0.89)95%CI, respectively. Oral anticoagulation discontinuation remained insignificant [hazard ratio 1.42(0.86-2.35)95%CI] in multivariable analysis. Beyond 3 months after RFA 87 (2.1%) serious bleedings occurred; incidence rates with and without OAC were 0.99 (0.77-1.27)95%CI and 0.44 (0.29-0.65)95%CI, respectively. Oral anticoagulation therapy was significantly associated with serious bleeding risk [hazard ratio 2.05(1.25-3.35)95%CI]. In an age- and gender-matched cohort (1 : 4) of 15 848 non-ablated AF patients receiving rhythm-control therapy, thromboembolic rates with and without OAC were 1.34 (1.21-1.49)95%CI and 2.14 (1.98-2.30)95%CI, respectively. Adjusted incidence rate ratio was 0.53 (0.43-0.65)95%CI favouring RFA cohort. CONCLUSION: Thromboembolic risk beyond 3 months after RFA was relatively low compared with a matched non-ablated AF cohort. With cautious interpretation due to low number of events, serious bleeding risk associated with OAC seems to outweigh the benefits of thromboembolic risk reduction. Randomized studies are warranted to test our results.

Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study.

BACKGROUND: The optimal long-term antithrombotic treatment of patients with coexisting atrial fibrillation and stable coronary artery disease is unresolved, and commonly, a single antiplatelet agent is added to oral anticoagulation. We investigated the effectiveness and safety of adding antiplatelet therapy to vitamin K antagonist (VKA) in atrial fibrillation patents with stable coronary artery disease. METHODS AND RESULTS: Atrial fibrillation patients with stable coronary artery disease (defined as 12 months from an acute coronary event) between 2002 and 2011 were identified. The subsequent risk of cardiovascular events and serious bleeding events (those that required hospitalization) was examined with adjusted Cox regression models according to ongoing antithrombotic therapy. A total of 8700 patients were included (mean age, 74.2 years; 38% women). During a mean follow-up of 3.3 years, crude incidence rates were 7.2, 3.8, and 4.0 events per 100 person-years for myocardial infarction/coronary death, thromboembolism, and serious bleeding, respectively. Relative to VKA monotherapy, the risk of myocardial infarction/coronary death was similar for VKA plus aspirin (hazard ratio, 1.12 [95% confidence interval, 0.94-1.34]) and VKA plus clopidogrel (hazard ratio, 1.53 [95% confidence interval, 0.93-2.52]). The risk of thromboembolism was comparable in all regimens that included VKA, whereas the risk of bleeding increased when aspirin (hazard ratio, 1.50 [95% confidence interval, 1.23-1.82]) or clopidogrel (hazard ratio, 1.84 [95% confidence interval, 1.11-3.06]) was added to VKA. CONCLUSIONS: In atrial fibrillation patients with stable coronary artery disease, the addition of antiplatelet therapy to VKA therapy is not associated with a reduction in risk of recurrent coronary events or thromboembolism, whereas risk of bleeding is increased significantly. The common practice of adding antiplatelet therapy to oral VKA anticoagulation in patients with atrial fibrillation and stable coronary artery disease warrants reassessment.

Risk of gastrointestinal adverse effects of dabigatran compared with warfarin among patients with atrial fibrillation: a nationwide cohort study.

AIMS: To examine the risk of gastrointestinal adverse effects associated with dabigatran use compared with warfarin among patients with atrial fibrillation (AF). METHODS AND RESULTS: Patients with AF and no history of gastrointestinal diseases initiating dabigatran or warfarin were identified from Danish nationwide registries from 22 August 2011 until 31 December 2012. Patients were classified as naive or experienced users, according to prior use of oral anticoagulant (OAC) therapy. The risk of subsequent proton pump inhibitor (PPI) use, upper dyspepsia-like diagnoses (gastroesophageal reflux, gastritis, gastric, and duodenal ulcer) and gastrointestinal bleeding requiring hospitalization, gastroscopy, and discontinuation of dabigatran and warfarin was examined by cumulative incidence rates and multivariable adjusted Cox regression models. We identified five groups: OAC-naive warfarin (n = 4534); OAC-naive dabigatran 110 mg b.i.d. (dabigatran 110) (n = 1168); OAC-naive dabigatran 150 mg b.i.d. (dabigatran 150) (n = 1844); OAC-experienced dabigatran 110 (n = 1143); and OAC-experienced dabigatran 150 (n = 1748). Compared with OAC-naive warfarin, the rate of initiating PPIs was significantly increased for OAC-naive dabigatran 110 [hazard ratio (HR), 1.24; 95% confidence interval (CI), 1.02-1.50]. Other dabigatran regimes were not associated with a higher risk of initiating PPIs, upper dyspepsia-like diagnoses, gastrointestinal bleeding, or gastroscopy. The risk of discontinuation was increased for OAC-experienced dabigatran 150 (HR, 1.13; 95% CI, 1.02-1.25), but not for the other dabigatran-treated groups, relative to OAC-naive warfarin. CONCLUSION: Dabigatran was not associated with upper dyspepsia-like diagnoses or gastrointestinal bleeding requiring hospitalization, and gastroscopy. The risk of subsequent PPI use was increased for OAC-naive dabigatran 110 mg users, and the risk of discontinuation was increased for OAC-experienced dabigatran 150 mg users.

Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naïve atrial fibrillation patients: Danish nationwide descriptive data 2011-2013.

AIMS: Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted. METHODS AND RESULTS: Using Danish nationwide administrative registers, we identified all oral anticoagulation-naïve AF patients initiating oral anticoagulation from 22 August 2011 through 31 October 2013. Using logistic regression analysis, baseline characteristics and temporal utilization trends were compared between initiators of warfarin vs. one of the N OACs: dabigatran, rivaroxaban, or apixaban. We identified 18 611 oral anticoagulation-naïve AF patients of which 9902 (53%) initiated warfarin treatment, 7128 (38%) dabigatran, 1303 (7%) rivaroxaban, and 278 (1%) apixaban. Overall, 40% of newly initiated patients were started on dabigatran within the first 4 months of when the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and another 20% were started on either rivaroxaban or apixaban. Rivaroxaban and apixaban users generally had a higher predicted risk of stroke and bleeding compared with warfarin and dabigatran users. Older age, female gender, and prior stroke were some of the factors associated with NOAC use vs. warfarin, whereas chronic kidney disease, myocardial infarction, and heart failure showed the opposite association. CONCLUSION: Among oral anticoagulation-naïve AF patients initiated on oral anticoagulation in Denmark, warfarin initiation has declined since the introduction of dabigatran in August 2011. Dabigatran is the most frequently used alternative option to warfarin; however, use of rivaroxaban and apixaban is increasing. Patients initiated with rivaroxaban or apixaban in general have a higher predicted stroke and bleeding risks compared with warfarin or dabigatran initiators.