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Objective: Non-vitamin K oral anticoagulants (NOACs) require dose adjustment for renal function. We sought to investigate change in renal function over time in patients with atrial fibrillation (AF) and whether those on NOACs have appropriate dose adjustments according to its decline., Methods: We included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry treated with oral anticoagulation. Worsening renal function (WRF) was defined as a decrease of >20% in creatinine clearance (CrCl) from baseline. The US Food and Drug Administration (FDA)-approved package inserts were used to define the reduction criteria of NOACs dosing., Results: Among 6682 patients with AF from 220 sites (median age (25th, 75th): 72.0 years (65.0, 79.0); 57.1% male; median CrCl at baseline: 80.1 mL/min (57.4, 108.5)), 1543 patients (23.1%) experienced WRF with mean decline in CrCl during 2 year follow-up of -6.63 mL/min for NOACs and -6.16 mL/min for warfarin. Among 4120 patients on NOACs, 154 (3.7%) patients had a CrCl decline sufficient to warrant FDA-recommended dose reductions. Of these, NOACs dosing was appropriately reduced in only 31 (20.1%) patients. Compared with patients with appropriately reduced NOACs, those without were more likely to experience bleeding complications (major bleeding: 1.7% vs 0%; bleeding hospitalisation: 2.6% vs 0%) at 1 year., Conclusions: In the US practice, about one-fourth of patients with AF had >20% decline in CrCl over time during 2 year follow-up. As a result, about 3.7% of those treated with NOACs met guideline criteria for dose reduction, but of these, only 20.1% actually had a reduction., Competing Interests: Competing interests: TI: Research Grant from Boston Scientific. LA: Contract with Janssen and Novartis. GF: Consultant/Advisory Board support from Janssen Pharmaceuticals. BJG: Member of a Data Safety Monitoring Board for Mount Sinai St. Lukes, Boston Scientific Corporation, Teva Pharmaceutical Industries, St. Jude Medical, Janssen Research & Development, Baxter Healthcare Corporation and Cardiovascular Research Foundation. Consultant/Advisory Board for Janssen Scientific Affairs, Cipla Limited, Armetheon Inc and Medtronic. EMH: Consultant: Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Johnson & Johnson; Research Grant from Bristol-Myers Squibb/Pfizer, Johnson & Johnson. MDE: Consultant/Advisory Board for Boehringer Ingelheim, Daiichi-Sankyo, Pfizer, Bristol-Myers Squibb and Janssen Scientific Affairs. PRK: Consultant for Johnson & Johnson. JAR: Research support from Janssen Pharmaceuticals and Medtronic Inc. Consultancies with Medtronic Inc, Acesion Pharma Aps, and Correvio Pharma Corp. GN: Research Grant from Janssen. Consultant/Advisory Board for Janssen and Daiichi-Sankyo. PC: Employee of Janssen. Consultant for Optum Rx and Johnson & Johnson. KWM: Financial disclosures can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey. DES: Consultant/Advisory Board for Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Johnson & Johnson, Pfizer and Medtronic. Research Grants from Boehringer Ingelheim and Bristol-Myers Squibb. JF: Consultant/Advisory Board for Janssen Scientific. BAS: Research support from Boston Scientific and Janssen. Consult for Janssen. Speakers’ bureau income Biosense Webster. EDP: Research Grant from Janssen Pharmaceuticals and Eli Lilly. Consultant for Janssen Pharmaceuticals and Boehringer Ingelheim. JPP: Research grant from Agency for Healthcare Research and Quality, ARCA biopharma, Boston Scientific, Gilead Sciences, Janssen Pharmaceuticals, Johnson & Johnson, ResMed, Spectranetics and St Jude Medical. Consultant/Advisory Board for BMS/Pfizer, GlaxoSmithKline, Janssen Pharmaceuticals, Johnson & Johnson, Medtronic and Spectranetics., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The association with B-type natriuretic peptide (BNP), disease progression and outcomes in patients with atrial fibrillation (AF) has not been thoroughly investigated., Methods: We evaluated the association between BNP levels and outcomes, including AF progression, composite outcome of major adverse cardiovascular or neurological events (MACNE) and major bleeding, via pooled logistic regression and Cox frailty models in Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry. AF progression was defined as either paroxysmal becoming persistent or permanent, or persistent becoming permanent at any follow-up., Results: Among 13 375 patients with AF, 2797 with BNP values at baseline (median age (IQR), 72.0 (63.0-80.0) years; 43.0% women; median BNP, 238 (102-502) ng/L; 42.3% prior heart failure) were included in the models evaluating the association between BNP levels and MACNE or major bleeding. Of these, 1282 patients with paroxysmal or persistent AF at baseline were analysed in AF progression model. The likelihood of AF progression (adjusted OR, 1.11 for every 100 ng/mL; 95% CI 1.03 to 1.19) and MACNE (adjusted HR, 1.11 for every doubling in BNP values; 95% CI 1.01 to 1.22) increased with BNP concentration, while the elevated BNP values were not associated with increased risks of major bleeding. BNP values improved the risk prediction of AF progression and MACNE when added to conventional risk estimates., Conclusions: BNP levels are associated with increased risk of AF progression and cardiovascular outcomes in patients with AF. Further studies are required to assess whether biomarker-based risk stratification improves patient outcomes., Clinical Trial Registration: NCT01701817., Competing Interests: Competing interests: TI: research grant from JSPS Overseas Research Fellowship and Boston Scientific. LAA: contract with Janssen and Novartis. GCF: consultant/advisory board support from Janssen Pharmaceutical. BJG: member of a Data Safety Monitoring Board for Mount Sinai St Lukes, Boston Scientific, Teva Pharmaceutical Industries, St Jude Medical, Janssen Research & Development, Baxter Healthcare and Cardiovascular Research Foundation; consultant/advisory board for Janssen Scientific Affairs, Cipla, Armetheon and Medtronic. MDE: consultant/advisory board for Boehringer Ingelheim, Diachi Sanko, Pfizer, Bristol-Myers Squibb and Janssen Scientific Affairs. PRK: consultant for Johnson & Johnson. JAR: research grant from Janssen Pharmaceuticals; research support from Boehringer Ingelheim Pharmaceuticals and GlaxoSmithKline; consultancies with Sanofi, Gilead Sciences, CV Therapeutics, GlaxoSmithKline, Merck & Co, Cardiome Pharma, Boehringer Ingelheim Pharmaceuticals and Medtronic; speakers’ bureau income from Sanofi and Boehringer Ingelheim Pharmaceuticals. GVN: research grant from Janssen; consultant/advisory board for Janssen and Daiichi Sankyo. PSC: employee of Janssen; consultant for Optum Rx and Johnson & Johnson. KWM: financial disclosures can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey. DES: consultant/advisory board for Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Johnson & Johnson, Pfizer and Medtronic; research grants from Boehringer Ingelheim and Bristol-Myers Squibb. JVF: consultant/advisory board for Janssen Scientific. BAS: research support from Boston Scientific and Janssen; consult for Janssen; speakers’ bureau income from Biosense Webster. EDP: research grant from Janssen Pharmaceuticals and Eli Lilly; consultant for Janssen Pharmaceuticals and Boehringer Ingelheim. JPP: research grant from Agency for Healthcare Research and Quality, ARCA Biopharma, Boston Scientific, Gilead Sciences, Janssen Pharmaceuticals, Johnson & Johnson, ResMed, Spectranetics and St Jude Medical; consultant/advisory board for BMS/Pfizer, GlaxoSmithKline, Janssen Pharmaceuticals, Johnson & Johnson, Medtronic and Spectranetics. SK, KP, and RGB have no relationship(s) to disclose., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Chronic obstructive pulmonary disease (COPD) is associated with the development of atrial fibrillation (AF), and may complicate treatment of AF. We examined the association between COPD and symptoms, quality of life (QoL), treatment and outcomes among patients with AF., Methods: We compared patients with and without a diagnosis of COPD in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, a prospective registry that enrolled outpatients with AF not secondary to reversible causes, from both academic and community settings., Results: Among 9749 patients with AF, 1605 (16%) had COPD. Relative to patients without COPD, those with COPD were more likely to be older, current/former smokers (73% vs 43%), have heart failure (54% vs 29%) and coronary artery disease (49% vs 34%). Oral anticoagulant and beta blocker use were similar, whereas digoxin use was more common among patients with COPD. Symptom burden was generally higher, and QoL worse, among patients with COPD (median Atrial Fibrillation Effect on QualiTy-of-Life score 76 vs 83). Patients with COPD had higher risk of all-cause mortality (adjusted HR 1.52 (95% CI 1.32 to 1.74)), cardiovascular mortality (adjusted HR 1.51 (95% CI 1.24 to 1.84)) and cardiovascular hospitalisation (adjusted HR 1.15 (95% CI 1.05 to 1.26)). Patients with COPD also had higher risk of major bleeding events (adjusted HR 1.25 (95% CI 1.05 to 1.50)). There did not appear to be associations between COPD and AF progression, ischaemic events or new-onset heart failure., Conclusions: Among patients with AF, COPD is associated with higher symptom burden, worse QoL, and worse cardiovascular and bleeding outcomes. These associations were not fully explained by cardiovascular risk factors, AF treatment or smoking history., Clinical Registration Number: NCT01165710., Competing Interests: Competing interests: LAA reports personal fees from Novartis and from Janssen during the conduct of the study, grants from PCORI, grants from American Heart Association, grants from NIH and personal fees from Boston Scientific, outside the submitted work. PSC reports consulting fees from Optum Rx and from American Heart Association, and grants from NIH. JVF reports personal fees from American College of Cardiology and from the National Cardiovascular Data Registry, personal fees from Janssen Pharmaceuticals, and grants from NHLBI, outside the submitted work. GCF reports personal fees from Janssen and personal fees from Medtronic, outside the submitted work. ASG reports that he has received a research grant through his institution from iRhythm Technologies. EMH reports personal fees from Advisory Boards: Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Medtronic, Pfizer and Portola; personal fees from honoraria for symposia: Bristol Myers Squibb, Boehringer Ingelheim, DOASENSE and Pfizer, outside the submitted work. KWM reports grants from Afferent, grants from Amgen, grants and personal fees from AstraZeneca, from Daiichi, grants from Ferring, grants from Google (Verily), grants and personal fees from Johnson & Johnson, grants from Medtronic, grants and personal fees from Merck, grants and personal fees from Novartis, grants from Sanofi, grants from St. Jude, personal fees from Ablynx, personal fees from BAROnova, from Bio2Medical, personal fees from Boehringer Ingelheim, personal fees from Bristol Myers Squibb, personal fees from Cardiometabolic Health Congress, personal fees from Cubist, personal fees from Eli Lilly, personal fees from Elsevier, personal fees from Epson, personal fees from Glaxo Smith Kline, personal fees from Mt. Sinai, personal fees from Myokardia, personal fees from Oculeve, personal fees from Portola, personal fees from Radiomeer, personal fees from Springer Publishing, personal fees from The Medicines Company, personal fees from Theravance, personal fees from UCSF, personal fees from Vindico, personal fees from WebMD, outside the submitted work. SDP reports grants from Janssen Pharmaceuticals, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Pfizer, grants from Food and Drug Administration, during the conduct of the study; grants and personal fees from Boston Scientific, personal fees from Medtronic, grants from Gilead, outside the submitted work. JAR reports grants from Janssen, during the conduct of the study; grants from Medtronic, personal fees from Portola, personal fees from Boehringer Ingelheim, outside the submitted work. DES reports personal fees from Johnson & Johnson, during the conduct of the study; grants from Bristol-Myers Squibb, grants from Boehringer Ingelheim, personal fees from Bristol-Myers Squibb, personal fees from Boehringer Ingelheim, personal fees from CVS Health, personal fees from Johnson & Johnson, personal fees from Merck, personal fees from Pfizer, personal fees from Medtronic, outside the submitted work. EDP reports grants and personal fees from Janssen Pharmaceuticals, outside the submitted work. JPP reports grants to his institution from ARCA Biopharma, Boston Scientific, Gilead Sciences, Janssen Pharmaceuticals, St. Jude Medical, and ResMed; consultancy fees from Amgen, Spectranetics, Medtronic, Allergan, Janssen Pharmaceuticals., (© 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.)