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Background and Aims: Trends in patient selection and use of pharmacotherapy prior to catheter ablation (CA) for supraventricular tachycardia (SVT) are not well described. This study examined temporal trends in patients undergoing first-time CA for regular SVT, including atrioventricular nodal re-entry tachycardia (AVNRT), accessory pathways (APs), and ectopic atrial tachycardia (EAT) on a nationwide scale in Denmark in the period 2001-2018., Methods and Results: Using Danish Nationwide registers, 9959 patients treated with first-time CA for SVT between 2001 and 2018 were identified, of which 6023 (61%) received CA for AVNRT, 2829 (28%) for AP, and 1107 (11%) for EAT. Median age was 55, 42, and 55 in the AVNRT, APs, and EAT group, respectively. The number of patients receiving CA increased from 1195 between 2001 and 2003 to 1914 between 2016 and 2018. The percentage of patients with a CHA 2 DS 2 -VASc score ≥ 2 increased in all patient groups. The number of patients who underwent CA with no prior use of antiarrhythmic- or rate limiting medicine increased significantly, though prior use of beta-blockers increased for AVNRT patients. Use of verapamil decreased in all three SVT groups (P < 0.05). Use of amiodarone and class 1C antiarrhythmics remained low, with the highest usage among EAT patients., Conclusion: Between 2001 and 2018, CA was increasingly performed in patients with SVT, primarily AVNRT- and EAT patients. The burden of comorbidities increased. Patients undergoing CA without prior antiarrhythmic- or rate-limiting drug therapy increased significantly. Use of beta-blockers increased and remained the most widely used drug., (© 2023. The Author(s).)

Background: Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events., Methods and Results: Using Danish nationwide registries, all patients with first-time ablation for atrial fibrillation were identified and included from 2010 to 2018. Patients were divided into 4 groups by diagnosis-to-ablation time: <1.0 year (early ablation), 1.0 to 1.9 years, 2.0 to 2.9 years, and >2.9 years (late ablation). The primary end point was atrial fibrillation recurrence after the 90-day blanking period, defined by admission for atrial fibrillation, cardioversions, use of antiarrhythmic drugs, or repeat atrial fibrillation ablations. The secondary end point was a composite end point of heart failure, ischemic stroke, or death, and each event individually. The study cohort consisted of 7705 patients. The 5-year cumulative incidence of atrial fibrillation recurrence in the 4 groups was 42.9%, 54.8%, 55.9%, and 58.4%, respectively. Hazard ratios were 1.20 (95% CI, 1.07-1.35), 1.29 (95% CI, 1.13-1.47), and 1.40 (95% CI, 1.28-1.53), respectively, with the early ablation group as reference. The hazard ratio for the combined secondary end point was 1.22 (95% CI, 1.04-1.44) in the late ablation group compared with the early ablation group., Conclusions: In patients undergoing ablation for atrial fibrillation, early ablation was associated with a significantly lower risk of atrial fibrillation recurrence. Furthermore, the associated risk of heart failure, ischemic stroke, or death was significantly lower in early-compared with late-ablation patients.

Aims: It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS)., Methods and Results: Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%)., Conclusion: Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements., Competing Interests: Conflict of interest: M.P. discloses the following relationships—advisory board: AstraZeneca, Janssen-Cilag, and Novo Nordisk; grant support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number CPD5Y-2022004-HF); and speaker honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, and Janssen-Cilag. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Relypsa, and Roche Diagnostics; speaker engagements with Novartis and Roche Diagnostics; and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. C.B. discloses the following relationships—speaker honorarium: Bayer. T.B.-S. discloses the following relationships—steering committee member of the Amgen-financed GALACTIC-HF trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘NUDGE-FLU’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-1’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-2’ trial, and steering committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial; advisory board: Sanofi Pasteur, Amgen, and GSK; speaker honorarium: Novartis, Sanofi Pasteur, and GSK; and research grants: GE Healthcare and Sanofi Pasteur. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNFOC0074083) and has received lecture and advisory board fees from Novo Nordisk. C.P.M. is supported by a grant from the National Institutes of Health (K23HL167659) and has received consulting fees/honorarium from Roche Diagnostics and Abbott Laboratories. L.K. discloses the following relationships—speaker honorarium from Novo Nordisk, Novartis, AstraZeneca, Boehringer, and Bayer. N.T.O. discloses the following relationships—research funding: Abbott and Shockwave. D.L.B. discloses the following relationships—advisory board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures and Hims; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. The other authors report no relevant disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To describe the population of patients diagnosed with hypertrophic cardiomyopathy (HCM) in Denmark and determine temporal trends in incidence and patient characteristics over time., Design: Nationwide retrospective cohort study., Setting: Danish nationwide administrative and clinical registers and databases., Participants: All patients aged ≥16 years diagnosed with HCM from 2005 to 2018., Outcomes Measures: Time trends in HCM diagnosis, patient characteristics, comorbidities and pharmacotherapy were identified and tested for significance using the Cochran-Armitage trend test., Results: 3856 HCM patients were included (median age 68 years (IQR 56-78)). Although there were more males (53%), females were older (72 years vs 63 years) and more likely to have their type of HCM classified as obstructive (54% vs 38%). A consistent rise in HCM cases per year was detected and there was a significant decline in prevalence of heart failure (2005: 20% to 2018: 12%, p<0.001) and ischaemic heart disease (2005: 31% to 2019: 16%, p≤0.001). Prevalence of atrial fibrillation and stroke remained notable and unchanged. Lastly, the rate of hospitalisations decreased over time (2005: 64% to 2016: 46%, p<0.001), while the rate of outpatient follow-up increased (2005: 81% to 2016: 87%, p 0.003)., Conclusion: There was a consistent rise in HCM cases with decreasing morbidity burden. Females were older at diagnosis and more likely to have their type of HCM classified as obstructive. The rate of outpatient follow-up is increasing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Conflict of interest: JH has received consultant fees and speaker honoraria from Biosense Webster, Medtronic, and Boston Scientific, and research funding from Biosense Webster and Medtronic. R.H.W. has received consultant fees, speaker honoraria, and research funding from Biosense Webster. All remaining authors have declared no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Atrial fibrillation (AF) and heart failure (HF) often coexist. However, whether AF onset before HF or vice versa is associated with the worst outcome remains unclear. A consensus of large studies can guide future research and preventive strategies to better target high-risk patients., Methods and Results: We included all Danish cases with the coexistence of AF and HF (2005-17) using nationwide registries. Patients were divided into three separate groups (i) AF before HF, (ii) HF before AF, or (iii) AF and HF diagnosed concurrently (±30 days). Adjusting landmark Cox analyses (index date was the time of the latter diagnosis of AF or HF) were used for evaluating the association of the three groups with a composite outcome of ischaemic stroke or death. Among a total of 49 042 patients included, 40% had AF before HF, 27% had HF before AF, and 33% had AF and HF diagnosed concurrently. The composite endpoint accrued more often in patients with HF before AF compared to the two other groups (<0.001), and this remained significant in the adjusted analyses with hazard ratios (95% confidence intervals) of 1.26 (1.22-1.30) compared to AF before HF. Finally, antihypertensive treatment, oral anticoagulants, amiodarone, statins, and AF ablation were associated with a lower hazard ratio of the composite endpoint (all < 0.001)., Conclusions: In this large Danish national cohort, diagnosis of HF before AF was associated with an increased absolute risk of death compared to AF before HF and AF and HF diagnosed concurrently. Antihypertensive treatment, oral anticoagulants, amiodarone, statins, and AF ablation may improve prognosis., Competing Interests: Conflict of interest: P.M.O. acts as an advisor to Prolaio Inc. All remaining authors have declared no conflicts of interest.., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Long-term prognostic implications of serial high-sensitivity troponin concentrations in subjects with suspected acute coronary syndrome are unknown., Methods and Results: Individuals with a first diagnosis of myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019 who underwent two high-sensitivity troponin-T (hsTnT) measurements 1-7 h apart were identified through Danish national registries. Absolute and relative risks for death at days 0-30 and 31-365, stratified for whether subjects had normal or elevated hsTnT concentrations, and whether these concentrations changed by <20%, > 20 to 50%, or >50% in either direction from first to second measurement, were calculated through multivariable logistic regression with average treatment effect modeling. Of the 28 902 individuals included, 2.8% had died at 30 days, whereas 4.9% of those who had survived the first 30 days died between days 31-365. The standardized risk of death was highest among subjects with two elevated hsTnT concentrations (0-30 days: 4.3%, 31-365 days: 7.2%). In this group, mortality was significantly higher in those with a > 20 to 50% or >50% rise from first to second measurement, though only at 30 days. The risk of death was very low in subjects with two normal hsTnT concentrations (0-30 days: 0.1%, 31-365 days: 0.9%) and did not depend on relative or absolute changes between measurements., Conclusions: Individuals with suspected acute coronary syndrome and two consecutively elevated hsTnT concentrations consistently had the highest risk of death. Mortality was very low in subjects with two normal hsTnT concentrations, irrespective of changes between measurements., Competing Interests: Conflict of interest: M.P. discloses the following relationships—Advisory Board: AstraZeneca, Janssen-Cilag; Grant Support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number: CPD5Y-2022004-HF); Speaker Honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, Janssen-Cilag. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, speaker engagements with AstraZeneca, Novartis, and Roche Diagnostics, and participates on clinical trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. C.B. discloses the following relationships—speaker honorarium: Bayer. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNFOC0074083) and has received lecture and advisory board fees from Novo Nordisk. T.B.-S. discloses the following relationships—Steering Committee member of the Amgen financed GALACTIC-HF trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘NUDGE-FLU’ trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘DANFLU-1’ trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘DANFLU-2’ trial, Steering Committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial, Advisory Board: Sanofi Pasteur, Amgen and GSK, speaker honorarium: Novartis, Sanofi Pasteur and GSK, Research grants: GE Healthcare and Sanofi Pasteur. L.K. discloses the following relationships—speaker honorarium from Novo Nordisk, Novartis, AstraZeneca, Boehringer, and Bayer. N.T.O. discloses the following relationships—research funding: Abbott, Shockwave. D.L.B. discloses the following relationships—advisory board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. The other authors report no relevant disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Cancer is a well-known risk factor of venous thromboembolism (VTE). Some cancers are believed to be more thrombogenic. The purpose of this study was to investigate the characteristics of patients with incident gastrointestinal cancers (GI) and their associated 1-year risk and timing of venous thromboembolic events and the 1-year mortality., Methods: This study was a retrospective cohort study. Through Danish nationwide registries, all patients with first-time GI cancer diagnosis from 2008 to 2018 were identified. Incident VTE events were identified within a 1-year follow-up after GI cancer diagnosis using the Aalen-Johansen estimator. Cox proportional-hazard models were applied to investigate risk factors for VTE events and the impact of VTE on mortality., Results: A total of 87 069 patients were included and stratified by cancer types: liver (5.8%), pancreatic (12.0%), gastric (6.9%), small intestinal (1.9%), colorectal (61.8%), oesophageal (7.3%) and gallbladder (3%). Most VTE events happened close to onset of the cancer diagnosis with declining events by time. The 1-year cumulative incidence of VTE differed according to cancer type with pancreatic cancer being most thrombogenic (7.8%), and colorectal and liver cancer being the least (3.6%). Prior VTE, heart failure, chronic obstructive pulmonary disease (COPD), liver disease, chronic kidney disease (CKD) and diabetes increased the VTE risk. Overall, the patients with GI cancer had high 1-year mortality of 33.3% with patients with pancreatic cancer having the highest mortality (70.3%)., Conclusion: We found that most VTE events happen close to onset of the GI cancer diagnosis and thrombogenicity differed by type of GI cancer, ranging from 7.8% in patients with pancreatic cancer to 3.6% in colorectal and patients with liver cancer. Prior VTE, heart failure, COPD, liver disease, CKD and DM were associated with increased risk of VTE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Atrial fibrillation (AF) is a predominant risk factor of ischaemic stroke and treatment with oral anticoagulants (OACs) is recommended in all patients with risk factors. This study sought to examine treatment patterns of OACs in older patients with AF., Design: Retrospective, cross-sectional study., Setting: Danish nationwide administrative and clinical registers and databases., Participants: A total of 40 027 patients, > 75 years of age, after their first hospital contact due to AF between 2010 and 2018., Primary and Secondary Outcomes Measures: The primary event of interest was claimed prescriptions for OACs within 180 days after first hospital contact due to AF. Proportions of patients treated with OACs were estimated and clinical factors associated with the probability of receiving OAC treatment were identified using adjusted logistic regression models., Results: A total of 40 027 patients were included with a slight majority of women (54%). The median age was 81 years (IQR 78-86). We found that an overall 32 235 patients (81%) were prescribed an OAC after their first hospital contact due to AF with a marked increase in the proportion of patients treated from 2010 to 2018. Factors related to a decreased probability of receiving treatment were bleeding risk factors such as a history of haemorrhagic stroke (OR 0.21, 95% CI 0.16 to 0.27), any bleeding (OR 0.58, 95% CI 0.53 to 0.62) as well as markers of frailty such as osteoporosis (OR 0.78, 95% CI 0.71 to 0.85)., Conclusion: In this large nationwide study, we found that in older patients with AF, the overall rates of OAC prescription were generally high (~80%) and increasing during the last decade. Factors associated with not receiving guideline recommended OAC treatment were generally related to bleeding risk factors or frailty., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE)., Methods: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores)., Results: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses., Conclusion: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating., Gov Id: NCT04377035., (© 2021. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Aim: To determine the risk of adverse outcomes across the spectrum of glycated haemoglobin (HbA1c) levels among hospitalized COVID-19 patients with and without diabetes., Materials and Methods: Danish nationwide registries were used to study the association between HbA1c levels and 30-day risk of all-cause mortality and the composite of severe COVID-19 infection, intensive care unit (ICU) admission and all-cause mortality. The study population comprised patients hospitalized with COVID-19 (3 March 2020 to 31 December 2020) with a positive polymerase chain reaction (PCR) test and an available HbA1c ≤ 6 months before the first positive PCR test. All patients had at least 30 days of follow-up. Among patients with diabetes, HbA1c was categorized as <48 mmol/mol, 48 to 53 mmol/mol, 54 to 58 mmol/mol, 59 to 64 mmol/mol (reference) and >64 mmol/mol. Among patients without diabetes, HbA1c was stratified into <31 mmol/mol, 31 to 36 mmol/mol (reference), 37 to 41 mmol/mol and 42 to 47 mmol/mol. Thirty-day standardized absolute risks and standardized absolute risk differences are reported., Results: We identified 3295 hospitalized COVID-19 patients with an available HbA1c (56.2% male, median age 73.9 years), of whom 35.8% had diabetes. The median HbA1c was 54 and 37 mmol/mol among patients with and without diabetes, respectively. Among patients with diabetes, the standardized absolute risk difference of the composite outcome was higher with HbA1c < 48 mmol/mol (12.0% [95% confidence interval {CI} 3.3% to 20.8%]) and HbA1c > 64 mmol/mol (15.1% [95% CI 6.2% to 24.0%]), compared with HbA1c 59 to 64 mmol/mol (reference). Among patients without diabetes, the standardized absolute risk difference of the composite outcome was greater with HbA1c < 31 mmol/mol (8.5% [95% CI 0.5% to 16.5%]) and HbA1c 42 to 47 mmol/mol (6.7% [95% CI 1.3% to 12.1%]), compared with HbA1c 31 to 36 mmol/mol (reference)., Conclusions: Patients with COVID-19 and HbA1c < 48 mmol/mol or HbA1c > 64 mmol/mol had a higher associated risk of the composite outcome. Similarly, among patients without diabetes, varying HbA1c levels were associated with higher risk of the composite outcome., (© 2021 John Wiley & Sons Ltd.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Conflict of interest None declared., (Copyright © 2021. Published by Elsevier Inc.)

Background: Although troponin elevation is associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19), prognostic implications of serial troponin testing are lacking. We investigated the association between serial troponin measurements and adverse COVID-19 outcomes., Methods: Using Danish registries, we identified COVID-19 patients with a high-sensitivity troponin measurement followed by a second measurement within 1-24 h. All measurements during follow-up were also utilized in subsequent time-varying analyses. We assessed all-cause mortality associated with the absence/presence of myocardial injury (≥1 troponin measurement >99th percentile upper reference limit) and absence/presence of dynamic troponin changes (>20% relative change if first measurement elevated, >50% relative change if first measurement normal)., Results: Of 346 included COVID-19 patients, 56% had myocardial injury. Overall, 20% had dynamic troponin changes. In multivariable Cox regression models, myocardial injury was associated with all-cause mortality (HR = 2.56, 95%CI = 1.46-4.51), as were dynamic troponin changes (HR = 1.66, 95%CI = 1.04-2.64). We observed a low incidence of myocardial infarction (4%) and invasive coronary procedures (4%) among patients with myocardial injury., Conclusions: Myocardial injury and dynamic troponin changes determined using serial high-sensitivity troponin testing were associated with poor prognosis among patients with COVID-19. The risk of developing myocardial infarction requiring invasive management during COVID-19 hospitalization was low., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Manan Pareek discloses the following relationships – Advisory Board: AstraZeneca, Janssen-Cilag; Speaker Honorarium: AstraZeneca; Bayer; Boehringer Ingelheim, Janssen-Cilag. Dr. Deepak L. Bhatt discloses the following relationships - Advisory Board: Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Novartis, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co‑leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Lilly, Medtronic, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Takeda. The other authors report no relevant disclosures., (© 2022 The Authors.)

Aims: Older patients with atrial fibrillation (AF) are at risk of adverse outcomes, which is accentuated by comorbidities. We sought to examine the association between morbidity burden and the treatment of older AF patients., Methods and Results: Using Danish nationwide registers we included patients ≥70 years of age between 2010 and 2017 at their first hospitalization due to AF. Using multiple logistic regression models we examined the association between morbidity burden and the odds of receiving oral anticoagulants (OACs), anti-arrhythmic drugs (AADs), and rhythm-control procedures (direct current cardioversions and catheter ablations). A total of 48 995 patients were included with a majority of women (54%), with a median age of 80 years [interquartile range (IQR) 75-85], and a median morbidity burden of 2 comorbidities (IQR 1-3). Increasing morbidity burden was associated with decreasing odds of OAC treatment with patients having >5 comorbidities having the lowest odds [odds ratio (OR) 0.38, 95% confidence interval (CI) 0.35-0.42] compared to patients with low morbidity burden (0-1 comorbidities). Having >5 comorbidities were associated with increased odds of AAD treatment (OR 1.90, 95% CI 1.64-2.21) and decreased odds of AF procedures (OR 0.39, 95% CI 0.31-0.48), compared to patients with a low morbidity burden (0-1 comorbidities). Examining morbidity burden continuously revealed similar results., Conclusions: In older AF patients, multimorbidity was associated with lower odds of receiving OACs and rhythm-control procedures but increased odds of AADs. This presents a clinical conundrum as multimorbid patients potentially benefit the most from treatment with OACs., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs) have an increased risk of bleeding including haematuria. In the general population, gross haematuria is associated with urinary tract cancer. Consequently, we aimed to investigate the potential association between gross haematuria and urinary tract cancer in anticoagulated patients with AF., Methods and Results: Using Danish nationwide registers, we included Danish AF patients treated with OACs between 2001 and 2015. Non-parametric estimation and semi-parametric absolute risk regression were used to estimate the absolute risk of urinary tract cancer in patients with and without gross haematuria. We included 125 063 AF patients with a median age of 74 years (interquartile range 65-80) and a majority of males (57%). The absolute risk of gross haematuria 12 months after treatment initiation increased with age ranging from 0.37% [95% confidence interval (CI) 0.31-0.42] to 0.85% (95% CI 0.75-0.96) in the youngest and oldest age groups of ≤70 and >80 years of age, respectively. The 1-year risk of urinary tract cancer after haematuria ranged from 4.2% (95% CI 2.6-6.6) to 6.5% (95% CI 4.6-9.0) for patients in age group >80 and 71-80 years, respectively. Gross haematuria conferred large risk ratios of urinary tract cancer when comparing patients with and without haematuria across all age groups., Conclusion: Gross haematuria was associated with clinically relevant risks of urinary tract cancer in anticoagulated patients with AF. These findings underline the importance of meticulously examining anticoagulated patients with haematuria., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.)

Background: Recurrence of atrial tachyarrhythmias after ablation of atrial fibrillation (AF) is common, although consensus guidelines advise against immediate re-ablation of "early recurrences" (occurring ≤ 90 days after ablation). However, recent studies show early recurrence is associated with "late recurrence" (occurring > 90 days) and question the duration of this "blanking period." We investigated incidence and timing of early recurrence in relation to late recurrence in a large nationwide cohort., Methods: From Danish nationwide registers, we included all patients aged 18 and older who underwent first-time ablation for AF between January 2005 and April 2017 and followed them for up to 2 years., Results: Of the total 7339 patients included (72% male; median age 62 years), 2801 (38%) experienced early recurrence. The odds of late recurrence were 2.34 times higher (95% confidence interval, 2.09-2.63; P < 0.001) given early recurrence, compared with those without early recurrence. In particular, both timing and frequency of early recurrences were associated with a significantly higher odds of late recurrence in a graded relationship: odds ratio (OR) 2.08/4.96/6.25 for early recurrences in the first/second/third month respectively (all P < 0.001); and OR 1.64/2.83/5.14 for those experiencing one/two/more than two episodes respectively (all P < 0.001); compared with those without early recurrence., Conclusion: In patients undergoing first-time ablation for AF, both the frequency and later onset of early recurrence are significantly associated with higher odds of late recurrence. This suggests the arbitrary blanking period should be abandoned in favor of a case-by-case assessment when evaluating candidates for re-ablation.

Objective: To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19., Design: Retrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender., Setting: All hospitals in Denmark., Participants: 1310 patients aged ≥18 years admitted to hospital with COVID-19 from 27th of February to 1st of May 2020, with available biochemistry data., Main Outcome Measures: A composite of death/ICU admission occurring within 30 days., Results: Of the 1310 patients admitted to hospital (54.6% men; median age 73.6 years), 352 (26.9%) experienced the composite endpoint and 263 (20.1%) died. For the composite endpoint, the absolute risks for moderately and severely elevated C reactive protein (CRP) were significantly higher, 21.5% and 39.2%, respectively, compared with 5.0% for those with normal CRP. Moderately and severely elevated leucocytes were significantly higher, 34.5% and 46.6% risk, respectively, compared with 23.2% for those with normal leucocytes. Moderately and severely decreased estimated glomerular filtration rates (eGFR) were significantly higher, 41.5% and 45.9% risk, respectively, compared with 30.4% for those with normal/mildly decreased eGFR. Normal and elevated ureas were significantly higher, 22.3% and 40.6% risk, respectively, compared with 7.3% for those with low urea. Elevated D-dimer was significantly higher, 31.8% risk, compared with 17.5% for those with normal D-dimer. Moderately and severely elevated troponins were significantly higher, 27.7% and 57.3% risk, respectively, compared with 9.4% for those with normal troponin. Elevated procalcitonin was significantly higher, 52.1% risk, compared with 28.0% for those with normal procalcitonin., Conclusion: In this nationwide study of patients admitted with COVID-19, elevated levels of CRP, leucocytes, procalcitonin, urea, troponins and D-dimer, and low levels of eGFR were associated with higher standardised absolute risk of death/ICU admission within 30 days., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Knowledge is scarce regarding how multimorbidity is associated with therapeutic decisions regarding oral anticoagulants (OACs) in patients with atrial fibrillation. Methods and Results We conducted a cross-sectional study of hospitalized patients with atrial fibrillation using the Get With The Guidelines-Atrial Fibrillation registry from 2013 to 2019. We identified patients ≥65 years and eligible for OAC therapy. Using 16 available comorbidity categories, patients were stratified by morbidity burden. A multivariable logistic regression model was used to determine the odds of receiving OAC prescription at discharge by morbidity burden. We included 34 174 patients with a median (interquartile range) age of 76 (71-83) years, 56.6% women, and 41.9% were not anticoagulated at admission. Of these patients, 38.6% had 0 to 2 comorbidities, 50.7% had 3 to 5 comorbidities, and 10.7% had ≥6 comorbidities. The overall discharge OAC prescription was high (85.6%). The prevalence of patients with multimorbidity increased from 59.7% in 2014 to 64.3% in 2019 ( P trend=0.002). Using 0 to 2 comorbidities as the reference, the adjusted odds ratio (95% CI) of OAC prescription were 0.93 (0.82, 1.05) for patients with 3 to 5 comorbidities and 0.72 (0.60, 0.86) for patients with ≥6 comorbidities. In those with ≥6 comorbidities, the most common reason for nonprescription of OACs were frequent falls/frailty (31.0%). Conclusions In a contemporary quality-of-care database of hospitalized patients with atrial fibrillation eligible for OAC therapy, multimorbidity was common. A higher morbidity burden was associated with a lower odds of OAC prescription. This highlights the need for interventions to improve adherence to guideline-recommended anticoagulation in multimorbid patients with atrial fibrillation.

Background: Recent randomised clinical trials have suggested prognostic benefits of catheter ablation in highly selected patients with atrial fibrillation (AF) and heart failure (HF)., Objectives: This study sought to identify the treatment effect associated with catheter ablation in a broad population of patients with AF and HF., Methods: Through nationwide administrative registers in Denmark, we estimated the 2-year average treatment effect (ATE) of catheter ablation for AF on a composite endpoint of HF readmission, stroke and all-cause mortality at 1-year and 5-year landmark analyses. The primary cohort was patients with AF before HF, and the second cohort of patients with HF before AF., Results: A total of 13 756 patients were included with 9904 patients in the primary cohort, and 3852 in the secondary. An ATE (95% CI) reduction of the composite endpoint of 7.0% (4.5% to 9.5%) was observed in the primary cohort and 11.8% (6.0% to 17.6%) in the secondary in the 1-year landmark analysis with a reduction in all-cause mortality of 5.8% (3.7%-7.8%) and 6.3% (0.9%-11.7%), respectively. At the 5-year landmark, catheter ablation was associated with reductions in the composite endpoint and all-cause mortality in the primary (4.7% (2.3% to 7.2%), and 3.6% (1.0% to 6.3%), respectively), but not in the secondary cohort., Conclusions: Ablation was associated with decreased risk of HF readmission, stroke and all-cause mortality in patients with AF and HF. The effect is most substantial in patients with AF before HF and with catheter ablation after 1 year from the diagnosis of both conditions., Competing Interests: Competing interests: FG is an advisor for Abbott, Carmat; Corvia (unpaid) speaker: Novartis, Astra, Orion Pharma; and investigator for Alnylam., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Recommendations regarding ibuprofen use in relation to coronavirus disease 2019 (COVID-19) have been conflicting. We examined the risk of severe COVID-19 between ibuprofen-prescribed and non-ibuprofen patients with COVID-19 in a nationwide register-based study of patients with COVID-19 in Denmark between the end of February 2020 and May 16, 2020. Patients with heart failure (n = 208), < 30 years (n = 575), and prescribed other nonsteroidal anti-inflammatory drugs (n = 57) were excluded. Patients with ibuprofen prescription claims between January 1, 2020, and before COVID-19 diagnosis or April 30, 2020 (last available prescription) were compared with patients without ibuprofen prescription claims. Outcome was a 30-day composite of severe COVID-19 diagnosis with acute respiratory syndrome, intensive care unit admission, or death. Absolute risks and average risk ratios comparing outcome for ibuprofen vs. non-ibuprofen patients standardized to the age, sex, and comorbidity distribution of all patients were derived from multivariable Cox regression. Among 4,002 patients, 264 (6.6%) had ibuprofen prescription claims before COVID-19. Age, sex, and comorbidities were comparable between the two study groups. Standardized absolute risks of the composite outcome for ibuprofen-prescribed vs. non-ibuprofen patients were 16.3% (95% confidence interval (CI) 12.1-20.6) vs. 17.0% (95% CI 16.0-18.1), P = 0.74. The standardized average risk ratio for ibuprofen-prescribed vs. non-ibuprofen patients was 0.96 (95% CI 0.72-1.23). Standardized absolute risks of the composite outcome for patients with ibuprofen prescription claims > 14 days before COVID-19 vs. ≤ 14 days of COVID-19 were 17.1% (95% CI 12.3-22.0) vs. 14.3% (95% CI 7.1-23.1). In conclusion, in this nationwide study, there was no significant association between ibuprofen prescription claims and severe COVID-19., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Aims: Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs., Methods and Results: Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64-78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04-0.18%) for NOACs and 0.13% (0.03-0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69-0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40-2.61)] and with VKA [HR 1.95 (95% CI 1.21-2.69)]., Conclusion: Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Research regarding out-of-hospital cardiac arrest (OHCA) survival of diabetes patients is sparse and it remains unknown whether initiatives to increase OHCA survival benefit diabetes and non-diabetes patients equally. We therefore examined overall and temporal survival in diabetes and non-diabetes patients following OHCA., Methods: Adult presumed cardiac-caused OHCAs were identified from the Danish Cardiac Arrest Registry (2001-2014). Associations between diabetes and return of spontaneous circulation upon hospital arrival and 30-day survival were estimated with logistic regression adjusted for patient- and OHCA-related characteristics., Results: In total, 28,955 OHCAs were included of which 4276 (14.8%) had diabetes. Compared with non-diabetes patients, diabetes patients had more comorbidities, same prevalence of bystander-witnessed arrests (51.7% vs. 52.7%) and bystander cardiopulmonary resuscitation (43.2% vs. 42.0%), more arrests in residential locations (77.3% vs. 73.0%) and were less likely to have shockable heart rhythm (23.5% vs. 27.9%). Temporal increases in return of spontaneous circulation and 30-day survival were seen for both groups (return of spontaneous circulation: 8.8% in 2001 to 22.3% in 2014 (diabetes patients) vs. 7.8% in 2001 to 25.7% in 2014 (non-diabetes patients); and 30-day survival: 2.8% in 2001 to 9.7% in 2014 vs. 3.5% to 14.8% in 2014, respectively). In adjusted models, diabetes was associated with decreased odds of return of spontaneous circulation (odds ratio 0.74 (95% confidence interval 0.66-0.82)) and 30-day survival (odds ratio 0.56 (95% confidence interval 0.48-0.65)) (interaction with calendar year p =0.434 and p =0.243, respectively)., Conclusion: No significant difference in temporal survival was found between the two groups. However, diabetes was associated with lower odds of return of spontaneous circulation and 30-day survival.

In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia. After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure. A chest X-ray showed signs of acute respiratory distress syndrome. Despite aggressive intensive care management, the patient died 7.5 hours after admission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia. In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea.

Background: In observational studies, case reports, and animal studies, amiodarone has been associated with incident cancer., Objective: The purpose of this study was to examine whether a dose-response relationship between amiodarone use and the risk of cancer could be ascertained in a large nationwide study cohort., Methods: Using nationwide registers, we included all Danish patients with atrial fibrillation (AF) treated with amiodarone from 1996 to 2014. Exposure was defined both by categories and as a continuous variable of the cumulative defined daily doses (cDDDs) of amiodarone. The associations between amiodarone cDDD and incident cancer, as well as organ-specific types of cancer (skin, liver, lung), were estimated using multivariable Cox regression models and reported as hazard ratios (HR) with 95% confidence intervals (CI) and using cubic restricted spline plots., Results: We included 18,503 patients with a median follow-up time of 8.1 years (interquartile range [IQR] 4.3-12.4). Median age was 70 years (IQR 63-77). A total of 2974 individuals developed cancer during follow-up. We found no association between increasing amiodarone exposure (cDDD 181-400 and cDDD >400) and the hazard of incident cancer (HR 0.95; 95% CI 0.87-1.04; and HR 1.01; 95% CI 0.92-1.10) with reference to patients with cDDD <181. Similar results were found when investigating specific cancer types (skin, liver, and lung) as well as cDDD as a continuous variable., Conclusion: In a large nationwide cohort of AF patients treated with amiodarone, we found no evidence of a dose-response relationship between cumulative dose of amiodarone and incident cancer risk., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify risk factors and to develop a predictive risk score for pacemaker implantation in patients with atrial fibrillation (AF)., Methods: Using Danish nationwide registries, patients with newly diagnosed AF from 2000 to 2014 were identified. Cox proportional-hazards regression computed HRs for risk factors of pacemaker implantation. A logistic regression was used to fit a prediction model for 3-month risk of pacemaker implantation and derived a risk score using 80% of the data and its predictive accuracy estimated using the remaining 20%., Results: Among 155 934 AF patients included, the median age (IQR) was 75 (65-83) and 51.3% were men. During a median follow-up time of 3.4 (1.2-5.0) years, 8348 (5.4%) patients received a pacemaker implantation. Risk factors of pacemaker implantation were (in order of highest risk first) age above 60 years, congenital heart disease, heart failure at age under 60 years, prior syncope, valvular AF, hypertension, ischaemic heart disease, male sex and diabetes mellitus. The derived risk score assigns points ranging from 1 to 14 to each of these risk factors. The 3-month risk of pacemaker implantation increased from 0.4% (95% CI: 0.2 to 0.8) at 1 point to 2.6% (95% CI: 1.9 to 3.6) at 18 points. Area under the receiver operator characteristics curve was 62.9 (95% CI: 60.3 to 65.5)., Conclusion: We highlighted risk factors of pacemaker implantation in newly diagnosed AF patients and created a risk score. The clinical utility of the risk score needs further investigation., Competing Interests: Competing interests: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Gunnar Gislason has ownership of stocks in Novo Nordisk Pharmaceuticals and reports research grants from AstraZeneca, Pfizer, Bristol Myers Squibb, Boerhringer Ingelheim and Bayer. Christian Torp-Pedersen declares grants for studies from Bayer. Other authors have no conflict of interest to declare., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort., Design: Retrospective cohort study., Setting: Danish nationwide registries., Participants: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year., Primary and Secondary Outcome Measures: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA 2 DS 2 VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes., Results: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA 2 DS 2 VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60)., Conclusion: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA 2 DS 2 VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding., Competing Interests: Competing interests: KF has received research grants Bayer/Janssen and AstraZeneca and Consulting/Fees Bayer, Sanofi/Regeneron and Verseon. FV has received honoraria for consulting and presentations from Bayer HealthCare, Boehringer Ibgelheimy, BMSPfizer and Daiichi-Sankyo. GHG has ownership of stocks in Novo Nordisk Pharmaceuticals and reports research grants from Pfizer, Bristol Myers Squibb, Boehringer Ingelheim and Bayer. CTP declares grants for studies from Bayer. Other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Management of atrial fibrillation (AF) with rate and/or rhythm control could lead to fall-related injuries and syncope, especially in the older AF population. We aimed to determine the association of rate and/or rhythm control with fall-related injuries and syncope in a real-world older AF cohort., Design: A retrospective cohort study., Setting: Danish nationwide administrative registries from 2000 to 2015., Participants: A total of 100 935 patients with AF aged 65 years or older claiming prescription of rate-lowering drugs (RLDs) and/or anti-arrhythmic drugs (AADs) were included. We compared the use of rate-lowering monotherapy with rate-lowering dual therapy, AAD monotherapy, and AAD combined with rate-lowering therapy., Measurements: Outcomes were fall-related injuries and syncope as a composite end point (primary) or separate end point (secondary)., Results: In this population, the median age was 78 years (interquartile range [IQR] = 72-84 y), and 53 481 (53.0%) were women. During a median follow-up of 2.1 years (IQR = 1.0-5.1), 17 132 (17.0%) experienced a fall-related injury, 5745 (5.7%) had a syncope, and 21 093 (20.9%) experienced either. Compared with rate-lowering monotherapy, AADs were associated with a higher risk of fall-related injuries and syncope. The incidence rate ratio (IRR) for the composite end point was 1.29 (95% confidence interval [CI]: 1.17-1.43) for AAD monotherapy and 1.46 [95% CI = 1.34-1.58] for AAD combined with rate-lowering therapy. When stratifying by individual drugs, amiodarone significantly increased the risk of fall-related injuries and syncope (IRR = 1.40 [1.26-1.55]). Compared with more than 180 days of rate-lowering monotherapy, a higher risk of all outcomes was seen in the first 90 days of any treatment; however, the greatest risk was in the first 14 days for those treated with AADs., Conclusion: In AF patients aged 65 years and older, AAD use was associated with a higher risk of fall-related injuries and syncope, and the risk was highest within the first 14 days for those treated with AADs. Only amiodarone use was associated with a higher risk. J Am Geriatr Soc 67:2023-2030, 2019., (© 2019 The American Geriatrics Society.)

Background: Management of atrial fibrillation (AF) with rate and rhythm therapy can cause bradyarrhythmia., Objectives: To assess overall risk, temporal risk, and subgroup at risk of bradyarrhythmia-related events by rate and/or rhythm therapy drugs., Methods: Using Danish nationwide registries, patients with AF between 2000 and 2014 were included if prescribed with rate-lowering drugs (RLDs) or antiarrhythmic drugs (AADs). An adjusted time-dependent Poisson regression model estimated the association between RLDs and AADs with a composite endpoint of pacemaker, temporary pacing, and bradyarrhythmia hospitalization. Secondary outcomes were each individual event., Results: Among 135,017 AF patients, 9196 (6.8%) patients experienced the composite endpoint with a median follow-up of 3.7 (interquartile range [IQR]: 1.6-7.0) years. Median age was 74 (IQR: 65-82) years and 47.6% were women. With rate-lowering monotherapy as the reference, the incidence rate ratios (IRR) (95% confidence interval) for the composite endpoint were 1.36 (1.29-1.43) for rate-lowering dual therapy, 1.62 (1.43-1.84) for antiarrhythmic monotherapy, and 2.49 (2.29-2.71) for AAD combined with RLDs. Similar trend was found for each secondary outcome. Particularly amiodarone increased the risk. This association was strongest within the first 2 weeks of treatment. In those treated with AAD combined with RLDs, high-risk populations were patients ≥70 years (IRR: 3.35 [2.51-4.45] compared to patients <60 years), and women (IRR: 1.35 [1.15-1.57], compared to men)., Conclusions: In real-world AF patients, rate-lowering dual therapy, antiarrhythmic monotherapy, and AADs combined with RLDs were positively associated with bradyarrhythmia-related events. The risk was highest in those treated with amiodarone, in the initial 2 weeks of treatment, in women, and in the elderly., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Given the novelty of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), little is known regarding overall implementation or clinical characteristics among patients who initiate treatment. We aimed to assess the total number of patients initiated on PCSK9i along with a description of the clinical characteristics and lipid lowering treatment (LLT) of such patients., Setting: A register-based descriptive cohort study of patients receiving a PCSK9i in the time period from 01 January 2016 to 31 March 2017 using a cross linkage between three nationwide Danish registers. Information regarding PCSK9i prescriptions, patient demographics, concurrent pharmacotherapy, comorbidities and previous coronary procedures was identified., Results: Overall, 137 patients initiated treatment with PCSK9i in the study period from 11 in the first quarter of 2016 to 40 in the first quarter of 2017. The majority had a history of ischaemic heart disease (IHD) (67.9%) with ischaemic stroke and diabetes mellitus being present in 7.3% and 16.8% of patients, respectively. All patients initiated on PCSK9i had been previously prescribed statin treatment with atorvastatin and simvastatin being most frequently prescribed in 53% and 36% of patients, respectively. The majority of patients had received both statins and ezetimibe (94.9%) and approximately half of these patients had also received bile acid sequestrant (45.3%). Clinical characteristics mainly differed in patients receiving triple LLT compared with patients not receiving triple LLT in the regards of heart failure., Conclusion: Patients treated with PCSK9i were rare, characterised by having IHD and had received various and intensive conventional LLT prior to PCSK9i initiation in agreement with current international guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Syncope could be related to high risk of falls and injury in adults, but documentation is sparse. We examined the association between syncope and subsequent fall-related injuries in a nationwide cohort., Methods: By cross-linkage of nationwide registers, all residents ≥18 years with a first-time diagnosis of syncope were identified between 1997-2012. Syncope patients were matched 1:1 with individuals from the general population. The absolute one-year risk of fall-related injuries, defined as fractures and traumatic head injuries requiring hospitalization, was calculated using Aalen-Johansen estimator. Ratios of the absolute one-year risk of fall-related injuries (ARR) were assessed by absolute risk regression analysis., Results: We identified 125,763 patients with syncope: median age 65 years (interquartile range 46-78). At one year, follow-up was complete for 99.8% where a total of 8394 (6.7%) patients sustained a fall-related injury requiring hospitalization, of which 1606 (19.1%) suffered hip fracture. In the reference group, 4049 (3.2%) persons had a fall-related injury. The one-year ARR of a fall-related injury was 1.79 (95% confidence interval 1.72-1.87, P<0.001) in patients with syncope compared with the reference group; however, increased ARR was not exclusively in older patients. Factors independently associated with increased ARR of fall-related injuries in the syncope population were: injury in past 12 months, 2.39 (2.26-2.53, P<0.001), injury in relation to the syncope episode, 1.62 (1.49-1.77, P<0.001), and depression, 1.37 (1.30-1.45, P<0.001)., Conclusion: Patients with syncope were at 80% increased risk of severe fall-related injuries within the year following discharge. Notably, increased risk was not exclusively in older patients., Competing Interests: AN has received research grants from P. Carl Petersen Foundation, Helsefonden, and the Department of Cardiology at Copenhagen University Gentofte Hospital. NC has received grants from The Danish Heart Foundation, The Danish Kidney Foundation, The Department of Cardiology at Gentofte Hospital and the Department of Nephrology at Herlev Hospital, Helen and Ejnar Bjoernows Foundation, The Danish Society of Nephrology and the Health Foundation. GG is supported by an unrestricted clinical research scholarship from the Novo Nordisk Foundation and has received research grants from AstraZeneca, Bristol Myers Squibb (BMS), Bayer, Boehringer-Ingelheim and Pfizer, and speaker honoraria from Pfizer, AstraZeneca and BMS, ouside the submitted work. CTP has received grants from Bayer and Biotronic outside the submitted work. JP has received grants from AstraZeneca, Bayer, Boehringer-Ingelheim, The Danish Heart Foundation, the Department of Cardiology at Copenhagen University Gentofte Hospital, and Axel Muusfeldt Foundation outside the submitted work. KBS has received unrestricted grants from Trygfonden Foundation outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The optimal treatment strategy when combining antiplatelets with oral anticoagulants in patients with atrial fibrillation (AF) and myocardial infarction (MI) or undergoing percutaneous coronary intervention (PCI) is unknown., Objectives: The authors investigated the risk of bleeding, ischemic stroke, MI, and all-cause mortality associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in combination with aspirin, clopidogrel, or both in patients with AF following MI and/or PCI., Methods: Danish nationwide registries were used to identify patients with AF who were admitted with a MI and/or underwent PCI, between August 2011 and June 2017, treated with OAC in combination with antiplatelet(s). Patients were followed for 12 months or until an outcome, study end, or death. Standardized absolute risks were estimated on the basis of outcome-specific Cox regression models adjusted for potential confounders. Average treatment effects were obtained as standardized absolute risk differences (ARD) in risks at 3 and 12 months using the g-formula., Results: Overall, 3,222 patients were included in the study population, of which 875 (27%) were treated with VKA+single antiplatelet therapy (SAPT), 595 (18%) were treated with DOAC+SAPT, 1,074 (33%) were treated with VKA+dual antiplatelet therapy (DAPT), and 678 (22%) were treated with DOAC+DAPT. At 3 months, there was a significant difference in the absolute risk of MI associated with DOAC+SAPT compared with VKA+SAPT (3-month ARD -1.53% (95% confidence interval: -3.08% to -0.11%), with no significant differences found regarding bleeding, ischemic stroke, and all-cause mortality. Compared with VKA+DAPT, DOAC+DAPT was associated with a significantly reduced risk of bleeding (3-month ARD -1.96%, 95% confidence interval: -3.46% to -0.88%), with no significant difference in the absolute risk of all-cause mortality, stroke, or MI., Conclusions: In a real-world population of AF patients with MI and/or after PCI, the authors found that DOAC in combination with DAPT was associated with a significantly decreased risk of bleeding and similar thromboembolic protection compared with VKA in combination with DAPT., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the risk of all-cause mortality, recurrent venous thromboembolism (VTE), and hospitalized bleeding in patients with VTE treated with either rivaroxaban or apixaban., Methods and Results: Using Danish nationwide registries, patients with VTE treated with rivaroxaban or apixaban in the period from 1 January 2015 to 30 June 2017 were identified. Standardized absolute risks were estimated based on outcome-specific Cox regression models, adjusted for potential confounders. A total of 8187 patients were included in the study, of which 1504 (18%) were treated with apixaban [50% males, median age 70 years; interquartile range (IQR) 56-80] and 6683 (82%) were treated with rivaroxaban (55% males, median age 67 years; IQR 53-76). The 180 days risk of all-cause mortality was 5.08% [95% confidence interval (95% CI) 4.08% to 6.08%)] in the apixaban group and 4.60% (95% CI 4.13% to 5.18%) in the rivaroxaban group [absolute risk difference: -0.48% (95% CI -1.49% to 0.72%)]. The 180 days risk of recurrent VTE was 2.16% (95% CI 1.49% to 2.88%) in the apixaban group and 2.22% (95% CI 1.89% to 2.52%) in the rivaroxaban group [absolute risk difference of 0.06% (95% CI -0.72% to 0.79%)]. The 180 days risk of hospitalized bleeding was 1.73% (95% CI 1.22% to 2.35%) for patients in the apixaban group and 1.89% (95% CI 1.56% to 2.20%) in the rivaroxaban group [absolute risk difference: 0.16% (95% CI -0.59% to 0.81%)]., Conclusion: In a nationwide cohort of 8187 patients with VTE treated with rivaroxaban or apixaban, there were no significant differences in the risks of all-cause mortality, recurrent VTE, or hospitalized bleeding.

Background: Evidence is conflicting as to the efficacy of direct oral anticoagulation (DOAC) and vitamin K antagonist (VKA) for prevention of myocardial infarction (MI)., Objectives: This study aimed to investigate the risk of MI associated with the use of apixaban, dabigatran, rivaroxaban, and VKA in patients with atrial fibrillation., Methods: Patients with atrial fibrillation were identified using Danish health care registers and stratified by initial oral anticoagulant treatment. Standardized absolute 1-year risks were estimated based on Cox regression for hazard rates of MI hospitalizations and mortality. Reported were absolute risks separately for the oral anticoagulation treatments and standardized to the characteristics of the study population., Results: Of the 31,739 patients included (median age, 74 years; 47% females), the standardized 1-year risk of MI for VKA was 1.6% (95% confidence interval [CI]: 1.3 to 1.8), apixaban was 1.2% (95% CI: 0.9 to 1.4), dabigatran was 1.2% (95% CI: 1.0 to 1.5), and rivaroxaban was 1.1% (95% CI: 0.8 to 1.3). No significant risk differences were observed in the standardized 1-year risks of MI among the DOACs: dabigatran versus apixaban (0.04%; 95% CI: -0.3 to 0.4), rivaroxaban versus apixaban (0.1%; 95% CI: -0.4 to 0.3), and rivaroxaban versus dabigatran (-0.1%; 95% CI: -0.5 to 0.2). The risk differences for DOACs versus VKA were all significant: -0.4% (95% CI: -0.7 to -0.1) for apixaban, -0.4% (95% CI: -0.7 to -0.03) for dabigatran, and -0.5% (95% CI: -0.8 to -0.2) for rivaroxaban., Conclusions: No significant risk differences of MI were found in the direct comparisons of DOACs, and DOACs were all associated with a significant risk reduction of MI compared with VKA., (Copyright © 2018. Published by Elsevier Inc.)

Background: We sought to determine whether insulin-sensitizing therapy (thiazolidinediones or metformin) decreased the risk of developing atrial fibrillation compared with insulin-providing therapy (insulin, sulfonylurea, or a meglitinide). Thiazolidinediones are insulin sensitizers that also decrease the inflammatory response. Because inflammation is a risk factor for atrial fibrillation, we hypothesized that treating diabetes with thiazolidinediones might decrease the risk of developing atrial fibrillation., Methods: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled patients with type 2 diabetes and documented coronary artery disease. All patients were randomized to insulin-sensitizing therapy or insulin-providing therapy., Results: A total of 2319 patients entered the study, with 1160 assigned to the insulin-sensitization strategy and 1159 assigned to the insulin-provision strategy. Over a median follow-up of 4.2 years, 90 patients (3.9%) developed new-onset atrial fibrillation. In the intention-to-treat analysis, the incidence of atrial fibrillation was 8.7 per 1000 person-years in patients assigned to insulin sensitization compared with 9.5 in patients assigned to insulin provision with a hazard ratio (HR) of 0.91 (95% confidence interval [CI], 0.60-1.38, P = .66). In a time-varying exposure analysis, the incidence rate per 1000 person-years was 7.2 while exposed to thiazolidinediones and 9.7 while not exposed to thiazolidinediones with an adjusted HR of 0.80 (95% CI, 0.33-1.94, P = .62). In a subset of patients matched on propensity to receive a thiazolidinediones, the HR was 0.75 (95% CI, 0.43-1.30, P = .30)., Conclusions: We did not find a significant reduction of atrial fibrillation incidence with use of thiazolidinediones., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To investigate temporal trends in the use of non-vitamin K oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in combination with aspirin and/or clopidogrel in patients with atrial fibrillation (AF) following acute myocardial infarction (MI) and/or percutaneous coronary intervention (PCI)., Methods: Using Danish nationwide registries, all patients with AF who survived 30 days after discharge from MI and/or PCI between 22 August 2011 and 30 September 2016 were identified., Results: A total of 2946 patients were included in the study population, of whom 1967 (66.8%) patients were treated with VKA in combination with antiplatelet(s) (VKA+aspirin n=477, VKA+clopidogrel n=439, VKA+aspirin+clopidogrel n=1051) and 979 (33.2%) patients were treated with NOAC in combination with antiplatelet(s) (NOAC+aspirin n=252, NOAC+clopidogrel n=218, NOAC+aspirin+clopidogrel n=509). The overall study population had a median age of 76 years [IQR: 69-82] and consisted of 1995 (67.7%) men. Patients with MI as inclusion event accounted for 1613 patients (54.8%). Patients with high CHA 2 DS 2 -VASc score(congestive heart failure, hypertension, age ≥75 years (2 points), diabetes mellitus, history of stroke/transient ischemic attack/systemic thromboembolism (2 points), vascular disease, age 65-75 years, and female sex) accounted for 132 2814 (95.5%) of patients, and patients with high HAS-BLED score (hypertension, abnormal renal/liver function, history of stroke, history of bleeding, age >65 years, non-steroidal anti-inflammatory drug usages, or alcohol abuse, leaving out labile international normalized ratio (not available), and use of antiplatelets (exposure variable)) accounted for 934 (31.7%) of patients. There was an increase from 10% in 2011 to 52% in 2016 in the use of NOACs in combination with antiplatelet(s)., Conclusion: From 2011 to 2016, the use of NOAC in combination with antiplatelet(s) increased in patients with AF following MI/PCI and exceeded the use of VKA in combination with antiplatelet(s) by 2016., Competing Interests: Competing interests: CS-P has nothing to declare. TAG has nothing to declare. LS has received funding for research from Boehringer Ingelheim. JLP has received funding for research from Boehringer Ingelheim and Bayer. CT-P declares research contracts with Bayer and Biotronic and speaker fees for Bayer and BMS. GHG has received funding for research from Boehringer Ingelheim, Pfizer, BMS, AstraZeneca and Bayer, and declares ownership of stocks in Lundbeck A/S, Novo Nordisk A/S and ALK Abello Pharmaceuticals. JBO has received speaker fees from Bristol-Myers Squibb, Boehringer Ingelheim, Bayer and AstraZeneca, previous funding for research from the Lundbeck Foundation, and current funding for research from the Bristol-Myers Squibb and the Capital Region of Denmark, Foundation for Health Research. ML has received speaker fees from Bristol-Meyer Squibb and Bayer. JSB has received research support from AstraZeneca and is a consultant for Merck, AstraZeneca and Janssen. ANB has nothing to declare. MLH has received speaker fees from Bristol-Meyer Squibb., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Differences in prevalence and prognostic information of cardiac troponin T (cTnT) and I (cTnI) concentrations in patients without acute coronary syndrome (ACS) are insufficiently investigated. High-sensitivity assays (hs-cTn) have led to an increased interest in hs-cTn for risk stratification. Here, we compare hs-cTnT and hs-cTnI in prediction of mortality patients without ACS., Method and Results: Patients aged >18 years, consecutively admitted to an emergency department (ED) were included. Blood was collected at admission and later analyzed with high-sensitivity assays for cTnT (Roche) and cTnI (Siemens). Troponin concentrations were reported as normal or increased according to the clinical cut-off value of 99th percentile as defined by the manufacturer. The primary outcome was all-cause mortality. Of the 822 participants (median, 65 years [48-77]; 428 female [52%]), 239 patients died. Median follow-up time was 3.0 years [2.1-3.0]. Elevation of hs-cTn was observed in 40% (n = 345) for hs-cTnT and 8% (n = 64) for hs-cTnI, p < 0.001. The relationship between elevated hs-cTn and mortality was strong for both hs-cTnT and hs-cTnI [HR 6.0 (95%CI: 2.9-12.6) vs. 5.1 (95%CI: 1.9-13.6)].There was no difference in prognostic accuracy for short-term mortality (30 days) between hs-cTnT and hs-cTnI. However, the prognostic accuracy for long-term mortality (1080 days) was superior for hs-cTnT than for hs-cTnI [area under the receivers operating curve (AUC) 0.81 vs 0.74, p < 0.001]., Conclusion: Both hs-cTnI and hs-cTnT were predictive for all-cause mortality. Notably, hs-cTnT measurement showed superior prognostic performance in predicting long-term all-cause mortality compared with hs-cTnI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40., Methods: Patients >18 years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after a single HD treatment., Results: A total of 306 patients were included. Median serum YKL-40 concentration was 238 µgL -1 (IQR: 193-291 µgL -1 ) before HD treatment and 198 µgL -1 (IQR: 147-258 µgL -1 ) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality after 2.8 years was 35.9%. Patients with serum YKL-40 in the highest quartile compared with the lowest quartile had a univariate HR of 4.0 (95% CI: 2.2-7.3, p < 0.001) for all-cause mortality which decreased to 2.4 (95% CI: 1.1-4.5, p = 0.01) in multivariate analysis. Time-dependent receiver operating characteristic curves showed that serum YKL-40 after HD treatment had significant higher area under the curves from 90 d (p = 0.004) and throughout the rest of the follow-up period when compared to serum YKL-40 before HD treatment., Conclusion: YKL-40 was highly elevated in patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations approximately one-sixth. YKL-40 measured after dialysis was independently associated with mortality in HD patients.

Background: The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM)., Methods: Through Danish nationwide registries, patients with NVAF and a PPM were identified from 2001 to 2012. Changes in concomitant pharmacotherapy and comorbidities were tested using the Cochran-Armitage trend test and linear regression. Patients with NVAF were identified to calculate the proportional amount of PPM implants., Results: A total of 12,231 NVAF patients with a PPM were included in the study, 55.6% of which were men. Median age was 78 years (interquartile range 70-84). From 2001 to 2012, the number of NVAF patients with a PPM increased from 850 to 1344, while the number of NVAF patients increased from 67,478 to 127,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p <0.001). Diabetes mellitus increased from 7.2% to 16.8% (p <0.001). Heart failure (HF) decreased from 36.7% to 29.3% (p = 0.010) and ischemic heart disease (IHD) decreased from 32.4% to 26.1% (p <0.001). Beta-blocker use increased from 38.1% to 58.0% (p <0.001), while digoxin and anti-arrhythmic drug use decreased over time., Conclusion: From 2001 to 2012, the absolute number of NVAF patients with a PPM increased while the proportional amount decreased. The number of NVAF patients receiving a PPM within one year of AF diagnosis decreased. The prevalence of DM increased, while the prevalence of HF and IHD was high but decreasing. The use of beta-blockers increased markedly, while use of digoxin and anti-arrhythmic drugs decreased over time.

Aims: Despite wide dissemination of automated external defibrillators (AEDs), bystander defibrillation rates remain low. We aimed to investigate how route distance to the nearest accessible AED was associated with probability of bystander defibrillation in public and residential locations., Methods: We used data from the nationwide Danish Cardiac Arrest Registry and the Danish AED Network to identify out-of-hospital cardiac arrests and route distances to nearest accessible registered AED during 2008-2013. The association between route distance and bystander defibrillation was described using restricted cubic spline logistic regression., Results: We included 6971 out-of-hospital cardiac arrest cases. The proportion of arrests according to distance in meters (≤100, 101-200, >200) to the nearest accessible AED was: 4.6% (n=320), 5.3% (n=370), and 90.1% (n=6281), respectively. For cardiac arrests in public locations, the probability of bystander defibrillation at 0, 100 and 200m from the nearest AED was 35.7% (95% confidence interval 28.0%-43.5%), 21.3% (95% confidence interval 17.4%-25.2%), and 13.7% (95% confidence interval 10.1%-16.8%), respectively. The corresponding numbers for cardiac arrests in residential locations were 7.0% (95% confidence interval -2.1%-16.1%), 1.5% (95% confidence interval 0.002%-2.8%), and 0.9% (95% confidence interval 0.0005%-1.7%), respectively., Conclusions: In public locations, the probability of bystander defibrillation decreased rapidly within the first 100m route distance from cardiac arrest to nearest accessible AED whereas the probability of bystander defibrillation was low for all distances in residential areas., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aims: Beta-blockers vary in pharmacodynamics and pharmacokinetic properties. It is unknown whether specific types are associated with increased perioperative risks. We evaluated perioperative risks associated with beta-blocker subtypes, overall and in patient subgroups., Methods and Results: We performed a Danish Nationwide cohort study, 2005-2011, of patients treated chronically with beta blocker (atenolol, bisoprolol, carvedilol, metoprolol, propranolol, or other) prior to non-cardiac surgery. Risks of 30-day all-cause mortality (ACM) and 30-day major adverse cardiovascular events (MACE) were estimated using adjusted logistic regression models and odds ratios with 95% confidence intervals. We identified 61 660 patients, most frequently treated with metoprolol (67% of patients, mean age 69 years, 49% males), atenolol (10% of patients, mean age 68 years, 36% males), or carvedilol (9% of patients, mean age 68 years, 60% males). The crude incidences of ACM and MACE were 4.1 and 3.5% in patients with metoprolol, 3.0 and 2.3% with atenolol, and 4.8 and 4.6% with carvedilol. In adjusted models, risks were not significantly different with atenolol (ACM; 1.10 [0.92-1.32], MACE; 1.08 [0.90-1.31]) or carvedilol (ACM; 0.99 [0.85-1.16], MACE; 1.07 [0.92-1.25]), compared with metoprolol. Risks of ACM were significantly lower in prior myocardial infarction patients treated with carvedilol (0.62 [0.43-0.87]) and no different in patients with uncomplicated hypertension (1.41 [0.83-2.40]). Risks did not differ in analyses stratified by age, surgery priority, duration of anaesthesia or surgery risk (all P for interaction >0.05)., Conclusion: Risks of ACM and MACE did not systematically differ by beta-blocker subtype. Findings may guide clinical practice and future trials., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aim: The aim of this study was to investigate the association between thiazolidinediones (TZDs) vs. other antidiabetic drugs and risk of atrial fibrillation (AF) in diabetic patients., Method and Results: Diabetes mellitus (diabetes) increases the risk of AF by approximately 34%. TZD is an insulin sensitizer that also has anti-inflammatory effects, which might decrease the risk of AF compared with other antidiabetic drugs. We used data from the Danish nationwide registries to study 108 624 patients with diabetes and without prior AF who were treated with metformin or sulfonylurea as first-line drugs. The incidence of AF was significantly lower with TZD as the second-line antidiabetic treatment compared with other second-line antidiabetic drugs (P < 0.001). The 10 year cumulative incidence [95% confidence interval (95% CI)] of AF was 6.2% (3.1-9.3%) with TZD vs. 10.2% (9.8-10.6%) with other antidiabetic drugs. The decreased risk of AF remained significant after adjusting for age, sex, and comorbidities with a hazard ratio (95% CI) of 0.76 (0.57-1.00), P = 0.047 associated with TZD treatment compared with other antidiabetic drugs., Conclusion: Use of a TZD to treat diabetes was associated with reduced risk of developing AF compared with other antidiabetic drugs as second-line treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Aims: The purpose of this study was to describe adherence with non-vitamin K antagonists (NOACs) and vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (NVAF)., Methods and Results: By linkage of Danish nationwide registers, we identified patients with NVAF who claimed a prescription of a NOAC (dabigatran, rivaroxaban, and apixaban), or a VKA. Adherence was evaluated according to Proportions of Days Covered, refill gaps, and switch in treatment. Adjusted analyses were calculated with logistic regression and Cox proportional hazard models. Between 2011 and 2014, 46 675 patients with NVAF claimed a prescription of anticoagulation (OAC): 57.3% used VKA, 29.8% dabigatran, 8.5% rivaroxaban, and 4.4% apixaban. During the first 180 days, PDC >80% was the highest among users of rivaroxaban. Compared with rivaroxaban, OR was 0.79 with apixaban (95% CI 0.69-0.92), 0.72 with dabigatran (95% CI 0.66-0.80), and 0.76 with VKAs (95% CI 0.69-0.83). HR for refill gaps between 7 and 89 days of length were (rivaroxaban as reference): apixaban 1.52(95% CI 1.36-1.69), dabigatran 1.72 (95% CI 1.60-1.85), and VKA 2.36(95% CI 2.20-2.52). Refill gaps of more than 89 days occurred in 11.5% of VKA recipients, with substantially lower rates for patients treated with NOAC. Switch between OACs was the highest in users of dabigatran (21.0%) and the lowest in users of apixaban (8.6%)., Conclusion: Among NVAF patients treated with OAC, 42.7% received a NOAC. PDC > 80%, and periods without refill gaps were the highest among users of rivaroxaban. Refill gaps occurred most often with VKA, switch was most common with dabigatran use., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Patients with atrial fibrillation (AF) have increased risk of thromboembolic events such as stroke and myocardial infarction (MI). Although it has been established that the efficacy of anticoagulation is superior to that of antiplatelet agents for stroke prophylaxis in AF, the optimal antithrombotic treatment remains uncertain for primary protection against MI., Objectives: The authors investigated the incidence of first-time MI in patients with AF according to antithrombotic treatment and estimated the risk of stroke and bleeding., Methods: Subjects with first-time AF diagnosed from 1997 to 2012 without history of coronary artery disease were identified using Danish nationwide administrative registries. Subjects were divided into time varying exposure groups according to antithrombotic treatment. The relative risks of outcomes were estimated by Poisson regression models., Results: A total of 71,959 patients (median 75 years of age; females: 47%). At baseline, 37,539 patients (52%) were treated with vitamin K antagonist (VKA) monotherapy, 25,458 (35%) with acetylsalicylic acid (ASA) monotherapy and 8,962 (13%) with dual-therapy (VKA + ASA). The incidence of MI was 3% (n = 2,275). Relative to the VKA-treated group, the associated risk of MI was significantly higher for ASA (incidence rate ratio [IRR]: 1.54; 95% confidence interval [CI]: 1.40 to 1.68) and dual-therapy (IRR: 1.22; 95% CI: 1.06 to 1.40). The bleeding risk was significantly higher for dual-therapy (IRR: 1.93; 95% CI: 1.81 to 2.07). The risk of stroke relative to that of VKA therapy was significantly higher for both ASA (IRR: 2.00; 95% CI: 1.88 to 2.12) and dual-therapy (IRR: 1.30; 95% CI: 1.18 to 1.43)., Conclusions: VKA monotherapy in patients with AF was associated with a lower risk of first-time MI and stroke than ASA monotherapy. Combination of ASA and VKA therapy was not associated with a lower risk of MI but was associated with increased bleeding risk., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Danish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apixaban 1,066, and dabigatran 96). Temporal trends showed a decrease in the initiation of VKA (p-value for decreasing trend, p < 0001) and an increase in the initiation of rivaroxaban and apixaban (p-value for increasing trend, p < 0001). By September 2016, 12%, 70%, 16%, and 2% of patients with VTE were initiated on VKA, rivaroxaban, apixaban, and dabigatran. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with one of the NOACs. In conclusion the initiation of rivaroxaban and apixaban is increasing significantly over time in patients with VTE. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with rivaroxaban or apixaban.

The approval of rivaroxaban has changed the landscape of treatment of venous thromboembolism (VTE). Little is known about the effect of rivaroxaban compared with vitamin K antagonists (VKA), when used in the everyday clinical practice. The aim of this study was to investigate the safety and effectiveness of rivaroxaban compared with VKAs among patients with VTE, using the Danish nationwide registries. All patients diagnosed with VTE and treated with either rivaroxaban or VKAs between 2013 and 2015 were included. A total of 12,318 patients were diagnosed with VTE and treated with VKAs [n=6,907] or rivaroxaban [n=5,411.]. Combined Cox regression analyses showed that the standardised absolute six-month risk of recurrent VTE was 3.03 % [95 % CI: 2.57 % to 3.48 %] in the rivaroxaban group and 3.13 % [95 % CI: 2.70 % to 3.56 %] in the VKA group (absolute risk difference of -0.11 % [95 % CI: -0.76 % to 0.54 %]). The standardised absolute six-months risk of bleeding was 2.28 % [95 % CI: 1.87 % to 2.67 %] for patients in the rivaroxaban group and 2.10 % [95 % CI: 1.78 % to 2.43 %] in the VKA group (absolute risk difference of 0.18 % [95 % CI: -0.34 % to 0.67]). In conclusion, rivaroxaban was associated with similar risk of recurrent VTE and bleeding compared with VKA.

Background: Identification of risk factors for venous thromboembolism (VTE) is of utmost importance to improve current prophylactic regimes and treatment guidelines. The extent to which a family history contributes to the risk of VTE needs further exploration., Objectives: To examine the relative rate of VTE in first-degree relatives compared with the general population., Methods: By crosslinking Danish nationwide registries we identified patients with VTE between 1978 and 2012, and their familial relations. The first member in a family to acquire VTE was defined as the proband. All first-degree relatives to probands were followed from the VTE date of the proband and until an event (VTE), death, emigration, 100 year birthday or end of study: 31st of December 2012, whichever came first. The relative rate of VTE was estimated by standardized incidence ratios (SIR) using time-dependent Poisson regression models, with the general population as a fixed reference., Results: We identified 70,767 children of maternal probands, 66,065 children of paternal probands, and 29,183 siblings to sibling probands. Having a maternal proband or a paternal proband were associated with a significantly increased VTE rate of 2.15 (CI: 2.00-2.30) and 2.06 (CI: 1.92-2.21), respectively. The highest estimate of VTE was observed among siblings (adjusted SIR of 2.60 [CI: 2.38-2.83]). Noteworthy, the rate of VTE increased for all first-degree relatives when the proband was diagnosed with VTE in a young age (≤ 50 years)., Conclusion: A family history of VTE was associated with a significantly increased rate of VTE among first-degree relatives compared with the general population., Competing Interests: Competing Interests: J. L. Pallisgaard has received funding for research from Boehringer Ingelheim and Bayer. C. Torp-Pedersen declare research contracts with Bayer and Biotronic and speaker fees for Bayer and BMS. G. H. Gislason has received funding for research from Boehringr Ingelheim, Pfizer, BMS, AstraZeneca and Bayer and declares ownership of stocks in Lundbeck A/S, Novo Nordisk A/S and ALK Abello pharmaceuticals. J. B. Olesen has received speaker fees from Bristol-Myers Squibb, Bayer, and Boehringer Ingelheim, and current funding for research from Bristol-Myers Squibb and The Capital Region of Denmark, Foundation for Health Research. E. L. Fosbøl was previously supported by a project specific research grant from Janssen Pharmaceuticals and has received funding for research from the Lundbeck Foundation and Bristol-Myers Squibb. A. Gundlund has received funding for research from Bristol-Myers Squibb. K. Aasbjerg has nothing to disclose. L. B. Oestergaard has nothing to disclose. C. Sindet-Pedersen has nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.