Search

Background Oral glucocorticoids and direct-acting oral anticoagulants (DOAC) have both been associated with a risk of gastrointestinal (GI) bleeding. However, drug safety, especially regarding the risk of bleeding, in relation to concomitant treatment with oral glucocorticoids and DOACs is insufficiently explored. Purpose We aimed to investigate the short-term risk of GI bleeding in patients with atrial fibrillation (AF) following concomitant treatment with DOACs and oral glucocorticoids. Methods Register-based, retrospective and nationwide Danish study including patients with AF and on DOAC treatment during 2012–2018. Patients were defined as exposed to oral glucocorticoids from the date of a redeemed prescription and 60 days forward. We associated concomitant treatment with GI bleeding and reported hazard ratios (HR) via a nested case-control design and standardized 60-day absolute risk adjusted for comorbidities using a cohort design. In both analyses, exposed were compared to non-exposed controls matched on age, sex, calendar year, follow-up time and DOAC agent. Results We included 98,376 patients (age [interquartile range]: 75 [68– 82], 44% females) with AF on DOAC treatment. The use of oral glucocorticoids among included patients was widespread with 16% redeeming at least one prescription within three years, 4% redeeming at least five (Figure 1A). Lung disease was the most frequent indication (Figure 1B). Concomitant treatment with DOACs and oral glucocorticoids was associated with an increased incidence of GI bleeding (total n=4,946) compared with only DOAC treatment, including a dose-response trend ( Conclusion Caution should be exercised when prescribing even short-term oral glucocorticoid treatment for DOAC treated patients, most notably in high doses and for patients with elevated bleeding risk. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Ib Mogens Kristiansens Almene FondandHelsefonden

Background Bradyarrhythmia is a known complication to direct current cardioversion (DC-cardioversion) in patients with atrial fibrillation (AF). However, whether concomitant treatment with anti-arrhythmic drugs (AADs) is associated with an increased risk of bradyarrhythmia in relation to the procedure is unknown. Purpose To investigate the short-term risk of bradyarrhythmia associated with AAD treatment in AF patients undergoing DC-cardioversion. Methods Using Danish nationwide registers, all AF patients treated with either an AAD (amiodarone, sotalol, dronedarone, flecainide, or propafenone) or rate-lowering drugs (beta-blocker, non- dihydropyridine calcium-antagonist, or digoxin) were identified at their first DC-cardioversion between 2001 and 2016. Patients were excluded if they were under 18 or above 100 years of age or had a pacemaker or implantable cardioverter defibrillator. The event of interest was a composite outcome of either a diagnosis of bradyarrhythmia (sinoatrial arrest, atrioventricular block, or unspecified bradycardia) or a procedure of pacemaker implantation. Patients were followed from the date of DC-cardioversion until event of interest, 90 days after the procedure, or at study end. Absolute risks of bradyarrhythmic events were estimated using the Aalen-Johansen estimator taking the competing risk of death into account. Hazard ratios (HR) with 95% confidence intervals (95% CI) of bradyarrhythmic events were computed using multivariable Cox models adjusted for age, sex, calendar year, as well as relevant comorbidity and concomitant medication. Results A total of 22,344 patients were included in the study with 3,224 (14%) individuals treated with an AAD. The median age was 67 years (interquartile range [IQR] 59–73) and most were males (69%). Patients treated with AADs were younger and had more ischemic heart disease, heart failure, and valvular disease. During follow-up we identified 601 cases of bradyarrhythmia. We found an absolute risk of bradyarrhythmic events at 90 days after cardioversion of 3.7% (95% CI 3.1–4.4) for patients treated with an AAD and 2.5% (95% CI 2.3–2.7) for patients treated with rate-lowering drugs (P Conclusion Using a large nationwide study population of patients with AF undergoing DC-cardioversion, concomitant treatment with AADs was associated with an increased risk of bradyarrhythmic events. Moreover, the absolute risks of bradyarrhythmic events after DC-cardioversion were higher than what has previously been reported. These data provide valuable insights aiding physicians in clinical decision making as well as informing patients prior to the procedure. Figure 1. Absolute risk and adjusted hazard ratio (HR) of bradyarrythmia. AAD: Anti-arrhythmic drugs. CI: Confidence Interval. Funding Acknowledgement Type of funding source: None

Aims The study aimed to estimate the risk of cardiac events in immune checkpoint inhibitor (ICI)-treated patients with lung cancer or malignant melanoma. Methods and results The study included consecutive patients with lung cancer or malignant melanoma in 2011–17 nationwide in Denmark. The main composite outcome was cardiac events (arrhythmia, peri- or myocarditis, heart failure) or cardiovascular death. Absolute risks were estimated and the association of ICI and cardiac events was analysed in multivariable Cox models. We included 25 573 patients with lung cancer. Of these, 743 were treated with programmed cell death-1 inhibitor (PD1i) and their 1-year absolute risk of cardiac events was 9.7% [95% confidence interval (CI) 6.8–12.5]. Of the 13 568 patients with malignant melanoma, 145 had PD1i and 212 had cytotoxic T-lymphocyte-associated protein-4 inhibitor (CTLA-4i) treatment. Their 1-year risks were 6.6% (1.8–11.3) and 7.5% (3.7–11.3). The hazard rates of cardiac events were higher in patients with vs. without ICI treatment. Within 6 months from 1st ICI administration, the hazard ratios were 2.14 (95% CI 1.50–3.05) in patients with lung cancer and 4.30 (1.38–13.42) and 4.93 (2.45–9.94) in patients with malignant melanoma with PD1i and CTLA-4i, respectively. After 6 months, HRs were 2.26 (1.27–4.02) for patients with lung cancer and 3.48 (1.91–6.35) for patients with malignant melanoma and CTLA-4i. Conclusions Among patients with lung cancer and malignant melanoma, ICI treated had increased rates of cardiac events. The absolute risks were higher in these data compared with previous pharmacovigilance studies (e.g. 1.8% peri-/myocarditis 1-year risk).

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.

Background Older patients with atrial fibrillation (AF) often have multiple chronic conditions adding complexity to treatment decisions. However, regarding older AF patients, the association between multimorbidity and quality of care has not been explored previously in a non-selected nationwide cohort. Purpose To investigate the association between morbidity burden and the treatment with oral anticoagulation therapy (OAC) and rhythm-control strategies in patients >65 years of age with incident AF in Denmark. Methods Using Danish nationwide registers, we identified all Danish AF patients >65 years of age hospitalized for incident AF between 2010 and 2016. Using logistic regression models, we estimated the association between morbidity burden (5 comorbidities) and the likelihood of receiving AF specific treatments. Estimates were reported as odds ratios with 95% confidence intervals (OR, 95% CI) with Results A total of 49,802 AF patients were eligible for inclusion, with a median age of 77.5 years (Interquartile range [IQR] 71.8–83.8) and 24,983 (50.2%) were male. A total of 25,181 (50.6%) patients had 5 comorbidities. The median CHA2DS2-VASc score ranged from 3 (IQR 2–3) to 5 (IQR 4–5) in patients with 5 comorbidities, respectively. Increasing morbidity burden was associated with decreasing odds of being treated with OAC therapy with the lowest odds in patients with >5 comorbidities (OR 0.39, 95% CI 0.34–0.45) compared with AF patients with Morbidity burden was associated with increased odds of being prescribed anti-arrhythmic medication with the highest odds in patients with >5 comorbidities (OR 2.50 95% CI 2.08–2.99). In contrast, having >5 comorbidities was associated with decreased odds of AF related procedures (OR 0.32, 95% CI 0.23–0.43) compared to patients with Forest plot of OAC initiation factors Conclusion Morbidity burden is strongly associated with OAC initiation and rhythm-control strategies in older patients with incident AF. Older AF patients with multimorbidity are less likely to be treated with OAC although these are the patients who benefit most from treatment. Therefore, initiatives and quality improvement programs should be done to close this important gap between clinical trials and clinical practice.

Purpose: ST-segment abnormalities are known to be common, but little more is known about their prevalence and possible prognostic implications. Therefore, we aimed to perform a reference study quantitatively assessing the age- and gender specific consequences of having ST-segment deviations. Methods: We evaluated precordial ST-segment deviations using computerized analysis of ECGs from 301,852 subjects (44.2% men) recorded in a primary care core laboratory. ST-segment deviations were divided into three categories of depression and three of elevation. Separate analyses were performed for men and women above and under the age of 65. Baseline data regarding medication and comorbidity as well as follow-up data were gathered with the use of Danish registries. Our end point was death from cardiovascular disease. Multivariable-adjusted hazard ratios for the different voltage-categories, in each of the precordial leads, were calculated using Cox P.H. model. All hazard ratios (HR) reported are with reference to an isoelectric ST-segment. Results: After a median follow-up period of 5.8 years, there were 8,282 cardiovascular deaths (CVD) and 25,574 deaths from non-cardiovascular causes. In general, increasing ST-depression was associated with an increased mortality in a dose-response manner in all precordial leads. This was most pronounced for women 150μV was associated with a HR of 10.48 (3.28-33.53). The same elevation in young men was associated with a HR of 0.76 (0.42-1.38). This gender difference was present in all leads except lead V1, where ST-elevation was associated with increased mortality for both men and women. ST-elevation >150μV in V1 was associated with a HR of 2.18 (1.15-4.14) for men >65 years of age and a HR of 2.34 (1.75-3.12) for women >65 years of age. Additionally, ST-elevations in lead V2 and V3 had a certain protective effect in men