Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

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

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

Blood-brain barrier permeable ß-blockers linked to lower risk of Alzheimer's disease in hypertension.

Alzheimer's disease is a neurodegenerative disorder in which the pathological accumulation of amyloid-ß and tau begins years before symptom onset. Emerging evidence suggests that ß-blockers (ß-adrenergic antagonists) increase brain clearance of these metabolites by enhancing CSF flow. Our objective was to determine whether ß-blocker treatments that easily cross the blood-brain barrier reduce the risk of Alzheimer's disease compared to less permeable ß-blockers. Data from the Danish national registers were used to identify a retrospective cohort of individuals with hypertension, and those treated with ß-blockers were included in the analysis. People with indications for ß-blocker use other than hypertension (e.g. heart failure) were only retained in a sensitivity analysis. ß-blockers were divided into three permeability groups: low, moderate and high. We used multivariable cause-specific Cox regression to model the effect of ß-blocker blood-brain barrier permeability on time to dementia outcomes, adjusting for baseline comorbidities, demographics and socioeconomic variables. Death was modelled as a competing risk. The 10-year standardized absolute risk was estimated as the averaged person-specific risks per treatment. In a cohort of 69 081 (median age = 64.4 years, 64.8% female) people treated with ß-blockers for hypertension, highly blood-brain barrier-permeable ß-blockers were associated with reduced risk of Alzheimer's disease versus low permeability ß-blockers (-0.45%, P < 0.036). This effect was specific to Alzheimer's diagnoses and did not extend to dementia in general. Propensity score analysis matching high and low blood-brain barrier-permeable patients also detected a decreased Alzheimer's risk (-0.92%, P < 0.001) in the high permeability group compared to the low, as did a 1-year landmark analysis (-0.57%, P < 0.029) in which events within the first year of follow-up were ignored as likely unrelated to treatment. Our results suggest that amongst people taking ß-blockers for hypertension, treatment with highly blood-brain barrier permeable ß-blockers reduces the risk of Alzheimer's disease compared to low permeability drugs. Our findings support the hypothesis that highly permeable ß-blockers protect against Alzheimer's disease by promoting waste brain metabolite clearance.

Patient Characteristics, Microbiology, and Mortality of Infective Endocarditis After Transcatheter Aortic Valve Implantation.

BACKGROUND: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is associated with high mortality and surgery is rarely performed. Thus, to inform on preventive measures and treatment strategies, we investigated patient characteristics and microbiology of IE after TAVI. METHODS: Using Danish nationwide registries, we identified patients with IE after TAVI, IE after non-TAVI prosthetic valve (nTPV), and native valve IE. Patient characteristics; overall, early (≤12 m), and late IE (>12 m) microbiology; and unadjusted and adjusted mortality were compared. RESULTS: We identified 273, 1022, and 5376 cases of IE after TAVI, IE after nTPV, and native valve IE. Age and frailty were highest among TAVI IE (4.8%; median age: 82 y; 61.9% frail). Enterococcus spp. were common for IE after TAVI (27.1%) and IE after nTPV (21.2%) compared with native valve IE (11.4%). Blood culture-negative IE was rare in IE after TAVI (5.5%) compared with IE after nTPV (15.2%) and native valve IE (13.5%). The unadjusted 90-day mortality was comparable, but the 5-year mortality was highest for IE after TAVI (75.2% vs 57.2% vs 53.6%). In Cox models adjusted for patient characteristics and bacterial etiology for 1-90 days and 91-365 days, there was no significant difference in mortality rates. CONCLUSIONS: Patients with IE after TAVI are older and frailer, enterococci and streptococci are often the etiologic agents, and are rarely blood culture negative compared with other IE patients. Future studies regarding antibiotic prophylaxis strategies covering enterococci should be considered in this setting.

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

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

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

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

Nationwide study of mortality and sudden cardiac death in young persons diagnosed with chronic kidney disease.

AIMS: The aim of this study was to compare short- and long-term risk of sudden cardiac death (SCD) among persons aged 18-49 years with and without chronic kidney disease (CKD). METHODS AND RESULTS: Using Danish nationwide health registries, all persons aged 18-49 years diagnosed with earlier stages of CKD or chronic kidney failure from 1 July 1995 through 2009 were identified. Non-exposed subjects matched on sex and birth-year were identified. All SCD in the Danish population aged 18-49 years in 2000-2009 have previously been identified using information from the Danish nationwide health registries, death certificates, and autopsy reports. In total, 9308 incident cases of earlier stage CKD and 1233 incident cases of chronic kidney failure were included. Among patients with earlier stage CKD, the absolute risk of SCD 1, 5, and 10 years after diagnosis was 0.14%, 0.37%, and 0.68%, respectively. Compared with age- and sex-matched subjects the corresponding relative risk (RR) was 20.3 [95% confidence interval (CI) 8.4-48.8], 7.1 (95% CI 4.2-12.0), and 6.1 (95% CI 3.8-9.7), respectively. Among patients with chronic kidney failure, the absolute 1-, 5-, and 10-year risk of SCD was 0.17%, 0.56%, and 2.07%, respectively. The corresponding RR was 12.5 (95% CI 1.4-111.6), 7.9 (95% CI 2.3-27.0), and 10.1 (95% CI 4.5-22.6). CONCLUSION: Persons with earlier stage CKD and chronic kidney failure had increased risk of SCD compared with the background population with a 6- to 20-fold increased risk of SCD. These findings underline the importance of early cardiovascular risk monitoring and assessment in persons with CKD.

Geographical inequalities in the decreasing 28-day mortality following incident acute myocardial infarction: a Danish register-based cohort study, 1987-2016.

BACKGROUND: Mortality following acute myocardial infarction (AMI) has decreased in western countries for decades; however, it remains unknown whether the decrease is distributed equally across the population independently of residential location. This study investigated whether the observed decreasing 28-day mortality following an incident AMI in Denmark from 1987 to 2016 varied geographically at municipality level after accounting for sociodemographic characteristics. METHODS: A register-based cohort study design was used to investigate 28-day mortality among individuals with an incident AMI. Global spatial autocorrelation (within sub-periods) was analysed at municipality level using Moran's I. Analysis of spatio-temporal autocorrelation before and after adjusting for sociodemographic characteristics was performed using logistic regression and conditional autoregressive models with inference in a Bayesian setting. RESULTS: In total, 368,839 individuals with incident AMI were registered between 1987 and 2016 in Denmark; 128,957 incident AMIs were fatal. The 28-day mortality decreased over time at national level with an odds ratio of 0.788 (95% credible interval (0.784, 0.792)) per 5-year period after adjusting for sociodemographic characteristics. The decrease in the 28-day mortality was geographically unequally distributed across the country and in a geographical region in northern Jutland, the 28-day mortality decreased significantly slower (4-12%) than at national level. CONCLUSIONS: During the period from 1987 to 2016, the 28-day mortality following an incident AMI decreased substantially in Denmark. However, in a local geographical region, the 28-day mortality decreased significantly slower than in the rest of the country both before and after adjusting for sociodemographic differences. Efforts should be made to keep geographical trend inequalities in the 28-day mortality to a minimum.

Time to Thrombolysis and Long-Term Outcomes in Patients With Acute Ischemic Stroke: A Nationwide Study.

Background and Purpose: It is well-established that increasing treatment delay reduces the benefits of thrombolysis in patients with acute ischemic stroke. However, most studies focus on short-term outcomes. This study examined long-term outcomes according to time to thrombolysis in patients with first-time ischemic stroke. Methods: In this nationwide cohort study, all Danish patients with first-time ischemic stroke treated with intravenous thrombolysis between 2011 and 2017 and alive at discharge were identified through the Danish Stroke Registry. The association between time from symptom onset to thrombolysis and the long-term rate of the composite of death and recurrent ischemic stroke was examined using multivariable Cox regression and restricted cubic spline analysis. Results: The study population included 6252 patients with first-time ischemic stroke treated with thrombolysis (median age, 69 years [25th­75th percentile 60­78 years], 60% men). The median follow-up was 2.5 years (25th­75th percentile 1.2­4.1 years). The median time to thrombolysis was 138 minutes (25th­75th percentile 101­185 minutes), and the median National Institutes of Health Stroke Scale score at presentation was 5 (25th­75th percentile 3­10). The absolute 3-year risk of the composite outcome was 19.0% (95% CI, 16.4%­21.8%) in the 0 to 90 minute group, 23.3% (21.8%­24.9%) in the 91 to 180 minute group, and 23.8% (21.6%­26.1%) in the 181 to 270 minute group. Compared with thrombolysis within 90 minutes, time to thrombolysis >90 minutes was associated with a higher rate of the composite outcome (91­180 minute: adjusted hazard ratio, 1.25 [95% CI, 1.06­1.48]; 181­270 minutes: adjusted hazard ratio, 1.35 [95% CI, 1.12­1.61]). In restricted cubic spline analysis, the rate of the composite outcome increased with increasing time to thrombolysis and leveled off after 138 minutes. Conclusions: In this nationwide cohort of patients with ischemic stroke, the long-term rate of the composite of death and recurrent ischemic stroke increased with increasing time from symptom onset to initiation of thrombolysis.

Echocardiographic predictors of long-term adverse cardiovascular outcomes in participants with and without diabetes mellitus: A follow-up analysis of the Copenhagen City Heart Study.

BACKGROUND: Previous studies have identified several echocardiographic markers of cardiac dysfunction in participants with diabetes mellitus, including E/e'. However, previous studies have been limited by short follow-up duration or low statistical power, and none have assessed whether echocardiographic predictors of adverse cardiovascular outcome differ between individuals with DM and individuals without DM. METHODS: A total of 1997 individuals from the general population without heart disease had an echocardiogram performed in 2001 to 2003. Diabetes was defined as HbA1c ≥6.5% (≥48 mmol/mol), non-fasted blood glucose ≥11.1 mmol/L or the use of glucose lowering medication. The end-point was a composite of heart failure (HF), ischemic heart disease (IHD) and cardiovascular death (CVD). RESULTS: At baseline, a total of 292 participants (15%) had diabetes. Median follow-up time was 12.4 years (interquartile-range: 9.8-12.8 years) and follow-up was 100%. During follow-up, 101 participants (35%) with diabetes and 281 participants without diabetes (16%) reached the composite end-point. The prognostic value of E/e' was significantly modified by diabetes (p for interaction: 0.003). In participants with diabetes, only E/e' remained an independent predictor of outcome in a final multivariable model adjusted for clinical and echocardiographic parameters (HR 1.08, 95% CI 1.00-1.17, p = 0.0041, per 1 increase). In participants without diabetes, left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and a' remained independent predictors of outcome when adjusted for clinical and echocardiographic parameters. In individuals with diabetes, only E/e' added incremental prognostic value to risk factors from the SCORE risk chart and the ACC/AHA Pooled Cohort Equation. CONCLUSION: In individuals with diabetes from the general population, E/e' is a stronger predictor of cardiovascular mortality and morbidity than in individuals without diabetes and contributes with incremental prognostic value in addition to established cardiovascular risk factors.

The importance of time in therapeutic range in switching from vitamin K antagonist to non-vitamin K antagonist oral anticoagulants in atrial fibrillation.

AIMS: Patients with non-valvular atrial fibrillation (NVAF) receiving vitamin K antagonists (VKAs) with time in therapeutic international normalized ratio (INR) range (TTR) <70%, despite good adherence, are by guidelines recommended to switch to non-VKA oral anticoagulants (NOACs). The aim was to assess if patients are switched from VKA to NOAC when TTR is <70% in a real-world setting. METHODS AND RESULTS: Non-valvular atrial fibrillation patients receiving VKA (1 January 2010 to 31 December 2012) were identified in nationwide registries. Time in therapeutic range was calculated by the Rosendaal method by a minimum of three INR values. Time in therapeutic range of patients continuing VKA (non-switchers) were compared with patients switched from VKA to dabigatran or rivaroxaban (switchers), the only NOACs available at that time. Factors associated with switching were analysed in a multivariable logistic regression model. 7276 patients with NVAF receiving VKA were included; of these, 6437 (88.5%) patients continued VKA [57.9% male, median age 76.7 years (Q1-Q3 68.9-83.5)] and 839 (11.5%) switched to NOAC [54.0% male, median age 76.5 years (Q1-Q3 68.4-83.6)]. No significant differences in CHA2DS2-VASc and HAS-BLED scores were seen between the groups. The mean TTR for non-switchers was 64.0 [standard deviation (SD) 27.8] and 52.9 (SD 28.1) for switchers. Among non-switchers, 51% had a TTR <70% vs. 69% among switchers. 85% of patients with TTR <70%, were not switched contrary to recommendations. Time in therapeutic range <70% was associated with the switch [odds ratio 2.28, 95% confidence interval (1.92-2.72)]. CONCLUSION: A TTR below 70% was associated with switching from VKA to NOAC, yet by guidelines, most patients were still not switched.

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

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

Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study.

Aims: We examined the risks of all-cause mortality, stroke, major bleeding, and recurrent traumatic injury associated with resumption of vitamin K antagonists (VKAs) and non-VKAs oral anticoagulants (NOACs) following traumatic injury in atrial fibrillation (AF) patients. Methods and results: This was a Danish nationwide registry-based study (2005-16), including 4541 oral anticoagulant (OAC)-treated AF patients experiencing traumatic injury (defined as traumatic brain injury, hip fracture, or traumatic torso or abdominal injury). Within 90 days following discharge from traumatic injury, 60.6% resumed VKA (median age = 80, CHA2DS2-VASc = 4, HAS-BLED = 2), 16.7% resumed NOAC (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 2), and 22.7% did not resume OAC treatment (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 3). Switch from VKA to NOAC occurred among 9.5%. Since 2009, the trend in OAC resumption increased (P-value <0.0001), in particular with NOACs (P-value <0.0001). Follow-up started 90 days after discharge, and time-varying multiple Cox regression analyses were used for comparisons. Compared with non-resumption, VKA and NOAC resumption were associated with lower hazard [95% confidence interval (CI)] of all-cause mortality [hazard ratio (HR) 0.48 (0.42-0.53) and HR 0.55 (0.47-0.66), respectively] and ischaemic stroke [HR 0.56 (0.43-0.72) and HR 0.54 (0.35-0.82), respectively], increased major bleeding hazard [HR 1.30 (1.03-1.64) and HR 1.15 (0.81-1.63), respectively], and similar hazard of recurrent traumatic injury [HR 0.93 (0.73-1.18) and HR 0.87 (0.60-1.27), respectively]. Conclusion: AF patients resuming VKA and NOAC treatment following traumatic injury have lower hazard of all-cause mortality and ischaemic stroke, increased hazard of major bleeding but without additional hazards of recurrent traumatic injury. Withholding OAC following a traumatic injury in AF patients may not be warranted.

The use of guideline recommended beta-blocker therapy in primary prevention implantable cardioverter defibrillator patients: insight from Danish nationwide registers.

Aims: We aimed to examine the use of guideline recommended beta-blocker therapy prior to and after primary prevention implantable cardioverter defibrillator (ICD) implantation in a 'real-life' setting. Methods and results: From the Danish Pacemaker and ICD Registry we identified all 1st-time primary prevention ICD and cardiac resynchronization therapy defibrillator (CRT-D) implantations in Denmark from 2007-12 (n = 2935). Use of beta-blocker, type and dose was acquired through the Danish Prescription Registry. According to guideline recommendations, we defined target daily doses as ≥50 mg carvedilol and ≥200 mg metoprolol. Prior to implantation 2427 of 2935 (83%) patients received beta-blocker therapy, with 2166 patients (89%) having initiated treatment 3 months or more prior to implantation. The majority of patients was prescribed carvedilol (52%) or metoprolol (41%). Patients on carvedilol reached target dosages more frequently than patients on metoprolol, with 39% of patients on carvedilol and 26% of patients on metoprolol at the time of implantation (P < 0.001 for all time-points). Increase in proportion of patients reaching target daily doses was observed for both carvedilol and metoprolol after ICD implantation. Carvedilol treatment was a strong predictor for being on target dose of BB at time of implant, as was treatment with angiotensin-converting enzyme inhibitors and/or spironolactone, no history of myocardial infarction, younger age and less pronounced heart failure symptoms. Conclusion: In a real-life setting of primary prevention ICD patients, 39% and 26% of patients were titrated to optimal target dose of carvedilol or metoprolol prior to implantation. A higher proportion of patients on carvedilol reached target dose, as compared with metoprolol.

Increased use of oral anticoagulants in patients with atrial fibrillation: temporal trends from 2005 to 2015 in Denmark.

AIM: The aim of this study is to examine temporal trends in the use oral anticoagulants (OAC) as stroke prophylaxis in patients with atrial fibrillation (AF) and to examine factors associated with OAC initiation. METHODS AND RESULTS: From Danish nationwide registries, we identified patients diagnosed with AF at Danish hospitals and outpatient clinics between January 2005 and June 2015. OAC initiation was assessed from prescription fills ±180 days from date of AF diagnosis. We identified a total of 108 410 patients with newly diagnosed AF. Before 2010, 40-50% initiated OAC treatment. From 2010, OAC initiation rates increased (P < 0.0001 for trend) and by June 2015, 66.5% of the incident AF patients were initiated on OAC (74.5% increase since December 2009). Increased OAC prescription was especially seen among females and 'fragile' patients (age > 75 years and high risk of stroke). The increased OAC initiation was accompanied by introduction and increased uptake of the NOACs. By the end of the study, NOACs accounted for 72.5% of all OACs prescribed in newly diagnosed AF patients. OAC initiation was associated with male gender, age 65-74 years, few comorbidities and increased risk of stroke. CONCLUSION: Since 2010, more incident AF patients in Denmark were initiated on OAC therapy with predominant NOAC prescription. The increase was pronounced among females, among patients at high risk of stroke, and among older patients.

Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation: a nationwide cohort study.

BACKGROUND: Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse. PURPOSE: To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE) and intracranial bleeding in AF. METHODS: Using Danish nationwide registries (2011-15), anticoagulant-naïve AF patients were identified when initiating VKA or an NOAC. Outcomes were stroke/TE and intracranial bleeding. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized differences in 1-year absolute risks. RESULTS: Overall, 43 299 AF patients initiated VKA (42%), dabigatran (29%), rivaroxaban (13%), and apixaban (16%). Mean CHA2DS2-VASc (SD) score was: VKA 2.9 (1.6), dabigatran 2.7 (1.6), rivaroxaban 3.0 (1.6), and apixaban 3.1 (1.6). Within patient-specific follow-up limited to the first 2 years, 1054 stroke/TE occurred and 261 intracranial bleedings. Standardized absolute risk (95% CI) of stroke/TE at 1 year after initiation of VKA was 2.01% (1.80% to 2.21%). In relation to VKA, the absolute risk differences were for dabigatran 0.11% (-0.16% to 0.42%), rivaroxaban 0.05% (-0.33% to 0.48%), and apixaban 0.45% (-0.001% to 0.93%). For the intracranial bleeding outcome, the standardized absolute risk at 1 year was for VKA 0.60% (0.49% to 0.72%); the corresponding absolute risk differences were for dabigatran -0.34% (-0.47% to - 0.21%), rivaroxaban -0.13% (-0.33% to 0.08%), and apixaban -0.20% (-0.38% to - 0.01%). CONCLUSIONS: Among anticoagulant-naïve AF patients, treatment with NOACs was not associated with significantly lower risk of stroke/TE compared with VKA, but intracranial bleeding risk was significantly lower with dabigatran and apixaban.

Incidence and prevalence of psoriatic arthritis in Denmark: a nationwide register linkage study.

OBJECTIVES: To examine the incidence and temporal trends of psoriatic arthritis (PsA) in the general population in Denmark. METHODS: Using nationwide registry data, we estimated the number of patients with incident PsA within each 1-year period between 1997 and 2011 and calculated the rate of PsA cases within gender and age subgroups. Incidence rates were presented per 100 000 person-years. RESULTS: There was a female predominance ranging from 50.3% (1998) to 59.2% (2010), and the mean age at time of diagnosis was 47-50 years. We identified a total of 12 719 patients with PsA (prevalence=0.22%), including 9034 patients where the PsA diagnosis was made by a rheumatologist (prevalence=0.16%). Incidence rates of PsA (per 100 000 person-years) increased from 7.3 in 1997 to a peak incidence of 27.3 in 2010. Incidence rates were highest for women and patients aged 50-59 years, respectively. The use of systemic non-biologic agents, that is, methotrexate, leflunomide, ciclosporin or sulfasalazine increased over the 15-year study course and were used in 66.3% of all patients. Biologic agents (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab or ustekinumab) were used in 17.7% of patients with PsA. CONCLUSIONS: We found a clear trend of rising PsA incidence on a national level. While the cause remains unclear, our findings might be explained by increased attention by patients and physicians.

Hyperprolactinemia and the Association with All-Cause Mortality and Cardiovascular Mortality.

Hyperprolactinemia has been suspected to increase mortality risk, but the available data are conflicting. The objective of this study was to estimate the association between hyperprolactinemia and all-cause and cardiovascular mortality among patients referred for assessment of prolactin. For this study, adults with no prio pituitary disease who underwent prolactin assessment at 3 university Hospitals in Denmark between 2001 and 2011 were included in a retrospective cohort study. A total of 3 633 patients with a median follow-up time of 5.3 years (IQR 2.7-5.7) were included. Mean (SD) age 39.7 (15.5) years and 78% female. 373/3 633 (10.3%) had hyperprolactinemia and during follow-up 330/3 633 (9.1%) patients died of any cause, and 113/3 633 (3.1%) patients died of cardiovascular causes. In males, hyperprolactinemia was associated with age-adjusted incidence rate ratio (IRR) of 1.86 for all-cause mortality (95% CI 1.22-2.82) and 2.55 (95% CI 1.43-4.55) for cardiovascular mortality. The IRR for all-cause mortality was reduced to 1.37 (0.90-2.08) when adjusted for the use of antipsychotic medication. The association between hyperprolactinemia and cardiovascular mortality remained after adjusting for confounders, for example, chronic renal failure, diabetes, and antipsychotic medication. In females, hyperprolactinemia was not associated with all-cause mortality (IRR 1.45; CI 0.86-2.47) or cardiovascular mortality (IRR 0.58; CI 0.14-2.39). In conclusion, hyperprolactinemia was associated with increased cardiovascular mortality in male patients. This association was not found in female patients. Focus on increased cardiovascular risk in males with hyperprolactinemia is warranted.

Nationwide Study on the Risk of Abdominal Aortic Aneurysms in Patients With Psoriasis.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a complex multifactorial disease associated with a high morbidity and mortality. Increased inflammation including T-helper 17 cell-mediated effects has been implicated in AAA pathogenesis. Psoriasis is considered to be a T-helper 17-driven chronic inflammatory disease and in view of potentially overlapping inflammatory mechanisms, we investigated the risk of AAA in patients with psoriasis in a nationwide cohort. APPROACH AND RESULTS: The study comprised all Danish residents aged ≥18 years followed up from January 1, 1997, until diagnosis of AAA, December 31, 2011, migration or death. Information on comorbidity, concomitant medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Incidence rates for AAA were calculated and incidence rate ratios adjusted for age, sex, comorbidity, medications, socioeconomic status, and smoking were estimated in Poisson regression models. A total of 5 495 203 subjects were eligible for analysis. During the study period, we identified 59 423 patients with mild psoriasis and 11 566 patients with severe psoriasis. The overall incidence rates of AAA were 3.72, 7.30, and 9.87 per 10 000 person-years for the reference population (23 696 cases), mild psoriasis (240 cases), and severe psoriasis (50 cases), respectively. The corresponding adjusted incidence rate ratios for AAA were increased in patients with psoriasis with incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (confidence interval, 1.21-2.32) for subjects with mild and severe disease, respectively. CONCLUSIONS: In a nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of AAA. The mechanisms and consequences of this novel finding require further investigation.

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

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