Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

BACKGROUND: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety. OBJECTIVES: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes. METHODS: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above. RESULTS: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%]). CONCLUSIONS: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.

Use of medical therapy and risk of clinical events according to frailty in heart failure patients - A real-life cohort study.

AIMS: Although recent randomized clinical trials have demonstrated the advantages of heart failure (HF) therapy in both frail and not frail patients, there is insufficient information on the use of HF therapy based on frailty status in a real-world setting. The aim was to examine how frailty status in HF patients associates with use of HF therapy and with clinical outcomes. METHODS AND RESULTS: Patients with new-onset HF between 2014 and 2021 were identified using the nationwide Danish registers. Patients across the entire range of ejection fraction were included. The associations between frailty status (using the Hospital Frailty Risk Score) and use of HF therapy and clinical outcomes (all-cause mortality, HF hospitalization, and non-HF hospitalization) were evaluated using multivariable-adjusted Cox models adjusting for age, sex, diagnostic setting, calendar year, comorbidities, pharmacotherapy, and socioeconomic status. Of 35 999 participants (mean age 69.1 years), 68% were not frail, 26% were moderately frail, and 6% were severely frail. The use of HF therapy was significantly lower in frailer patients. The hazard ratio (HR) for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation was 0.74 (95% confidence interval 0.70-0.77) and 0.48 (0.43-0.53) for moderate frailty and severe frailty, respectively. For beta-blockers, the corresponding HRs were 0.74 (0.71-0.78) and 0.51 (0.46-0.56), respectively, and for mineralocorticoid receptor antagonists, 0.83 (0.80-0.87) and 0.58 (0.53-0.64), respectively. The prevalence of death and non-HF hospitalization increased with frailty status. The HR for death was 1.55 (1.47-1.63) and 2.32 (2.16-2.49) for moderate and severe frailty, respectively, and the HR for non-HF hospitalization was 1.37 (1.32-1.41) and 1.82 (1.72-1.92), respectively. The association between frailty status and HF hospitalization was not significant (HR 1.08 [1.02-1.14] and 1.08 [0.97-1.20], respectively). CONCLUSION: In real-world HF patients, frailty was associated with lower HF therapy use and with a higher incidence of clinical outcomes including mortality and non-HF hospitalization.

Temporal trend of first-line drug choice and treatment continuity for hypertension among citizens 75 years or over - a register-based, cohort study.

BACKGROUND: Limited knowledge of antihypertensive treatment of the elderly potentially impedes effective strategies for hypertension management in this growing patient group. We aimed to investigate temporal trends for first-line drug choice for antihypertensive treatment and treatment continuity among patients ≥75 years from 2000 to 2021. METHODS: Using nationwide Danish registers, patients ≥75 years initiated for the first time on antihypertensive drugs: Angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), thiazides, or combinations, were identified. Patients with other indications than hypertension were excluded. Treatment continuity was described using claimed prescriptions the first 180 days following study entry. RESULTS: From 2000 to 2021, 170,769 patients (median age 80 years [interquartile range:77-84], 60.3% female) were included. From 2000 to 2003 to 2015-2021 the proportion of first-line drug choice increased for ACEi (8.7% to 14.9%), ARB (4.1% to 23.9%), and CCB (10.7% to 27.6%), decreased for thiazides (60.6% to 15.9%) and remained stable for BB (12.9% to 14.1%) and combinations (2.9% to 3.6%). For 157,457 patients alive after 180 days, discontinuation was highest among patients initiated on thiazides (28.3%) whereas most patients continued the same single drug regimen if they started on ACEi (55.2%), ARB (65.0%), BB (57.2%) or CCB (59.3%). CONCLUSIONS: From 2000 to 2021 thiazides have been replaced by ACEi, ARB and CCB. Thiazides had the lowest treatment continuity while ARB appeared preferred slightly over ACEi. Differences in adherence in relation to first-line drug choice may warrant scrutiny regarding recommendations for the elderly.

Impact of breast-, gastrointestinal-, and lung cancer on prognosis in patients with first-time pulmonary embolism: A Danish nationwide cohort study.

BACKGROUND: Pulmonary embolism (PE) is described as a prognostic factor in patients with cancer however, the prognostic impact of PE remains unknown. This study investigated, the 1-year prognosis following PE in patients with breast-, gastrointestinal-, or lung cancer stratified by cancer status. METHODS: All Danish patients with first-time PE from 2008 to 2018 were included. Cancer status was categorized as no cancer, history of cancer, non-active cancer and active cancer. Unadjusted and age-stratified 1-year risk of death was estimated using the Kaplan-Meier estimator. Cause of death was reported using the Aalen-Johansen method. RESULTS: Of 35,679 patients with PE, 18% had a breast-, gastrointestinal-, or lung cancer. Patients with cancer were older compared with no cancer (69.8 years [IQR: 56.2-79.8]). One-year risk of death (95% confidence interval) for active breast-, gastrointestinal-, and lung cancer was 49.5% (44.0%-54.9%), 75.0% (72.5%-77.4%) and 80.1% (78.0%-82.3%) respectively, compared with 18.9% (18.4%-19.3%) for no cancer. Age-stratified analysis revealed no association with increasing age in non-active lung cancer and all active cancers. Further, non-cardiovascular death accounted for an increasing proportion by cancer status (no cancer < history of cancer < non-active cancer < active cancer). CONCLUSIONS: One-year risk of death was dependent on both cancer type and status; no association with age was found for patients with active cancers. Non-cardiovascular death was leading in non-active and active cancers. Thus, the occurrence of first-time PE could be regarded as a marker of cancer severity for patients with breast-, gastrointestinal-, and lung cancer.

Trends in percutaneous left atrial appendage occlusion and 1-year mortality 2013-2021: A nationwide observational study.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) is increasingly used for stroke prevention in patients with atrial fibrillation and anticoagulant-related complications. Yet, real-life studies evaluating changes in patient characteristics and indications for LAAO remain scarce. METHODS: To evaluate changes in patient characteristics and indications for LAAO defined as 2-year history of intracerebral bleeding, any ischemic stroke/systemic embolism (SE), any non-intracerebral bleeding, other indication, and 1-year mortality. All patients undergoing percutaneous LAAO in Denmark from 2013 to 2021 were stratified into the following year groups: 2013-2015, 2016-2018, and 2019-2021. RESULTS: In total, 1465 patients underwent LAAO. Age remained stable (2013-2015: 74 years versus 2019-2021: 75 years). Patients' comorbidity burden declined, exemplified by CHA2DS2-VASc ≥4 and HAS-BLED ≥3 decreased from 56.7% and 63.7% in 2013-2015 to 40.3% and 45.8% in 2019-2021. Indications for LAAO changed over time with other indication comprising 44.7% in 2019-2021; up from 26.9% in 2013-2015. Conversely, fewer patients had an indication of any ischemic stroke/SE (2013-2015: 30.8% vs 2019-2021: 20.3%) or any non-intracerebral bleeding (2013-2015: 29.4% vs 2019-2021: 23.4%). 1-year mortality was 11.3% for any non-intracerebral bleeding and 6.2% for other indication. CONCLUSION: The LAAO patient-profile has changed considerably. Age remained stable, while comorbidity burden decreased during the period 2013-2021. LAAO is increasingly used in patients with no clinical event history and mortality differs according to indication. Selection of patients to LAAO should be done carefully, and contemporary real-life studies investigating clinical practice could add important insights.

Temporal Trends in the Initiation of Dialysis Among Patients With Heart Failure With or Without Diabetes: A Nationwide Study From 2002 to 2016.

BACKGROUND: The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time. METHODS AND RESULTS: Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF-related hospitalization, and all-cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person-years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person-years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF-related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80-2.39] and 2.93 [95% CI, 2.40-3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14-2.80] and 2.86 [95% CI, 2.32-3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33-3.10] and 3.30 [95% CI, 2.69-4.06] in 2012 to 2016). CONCLUSIONS: The IR of acute and chronic dialysis remained low compared with HF-related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2-fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and prevent adverse events.

Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study.

BACKGROUND AND AIMS: A rising number of countries allow physicians to treat chronic pain with medical cannabis. However, recreational cannabis use has been linked with cardiovascular side effects, necessitating investigations concerning the safety of prescribed medical cannabis. METHODS: Using nationwide Danish registers, patients with chronic pain initiating first-time treatment with medical cannabis during 2018-21 were identified and matched 1:5 to corresponding control patients on age, sex, chronic pain diagnosis, and concomitant use of other pain medication. The absolute risks of first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome were reported comparing medical cannabis use with no use. RESULTS: Among 1.88 million patients with chronic pain (46% musculoskeletal, 11% cancer, 13% neurological, and 30% unspecified pain), 5391 patients claimed a prescription of medical cannabis [63.2% women, median age: 59 (inter-quartile range 48-70) years] and were compared with 26 941 control patients of equal sex- and age composition. Arrhythmia was observed in 42 and 107 individuals, respectively, within 180 days. Medical cannabis use was associated with an elevated risk of new-onset arrhythmia {180-day absolute risk: 0.8% [95% confidence interval (CI) 0.6%-1.1%]} compared with no use [180-day absolute risk: 0.4% (95% CI 0.3%-0.5%)]: a risk ratio of 2.07 (95% CI 1.34-2.80) and a 1-year risk ratio of 1.36 (95% CI 1.00-1.73). No significant association was found for acute coronary syndrome [180-day risk ratio: 1.20 (95% CI 0.35-2.04)]. CONCLUSIONS: In patients with chronic pain, the use of prescribed medical cannabis was associated with an elevated risk of new-onset arrhythmia compared with no use-most pronounced in the 180 days following the initiation of treatment.

Temporal Trends in Patient Characteristics and Outcomes of Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement: A Nationwide Study.

With increased use of transcatheter aortic valve implantation (TAVI) in treatment of aortic stenosis, it is important to evaluate real life data trends in outcomes. This nationwide register-based study aimed to present an outlook on temporal trends in characteristics and outcomes, including mortality. First-time consecutive Danish patients who underwent TAVI from 2010 to 2019 were included in this study. The chi-square and Kruskal-Wallis tests were performed to assess the differences in the characteristics over time and Cochrane-Armitage trend tests were used to examine changes in complications and mortality. Between 2010 and 2019, 4,847 patients (54.6% men, median age 82 [quartile 1 to quartile 3: 77 to 85] years) underwent first-time TAVI. A statistically significant decrease over time was observed for preprocedural hypertension, ischemic heart disease, and heart failure, whereas preexisting chronic obstructive lung disease and preprocedural pacemaker remained stable. We observed a significant decrease in 30- and 90-day postoperative preprocedural pacemaker implantation from 2011 to 2017, with 15.1% and 15.9% in 2011 and 8.6% and 8.9% in 2017, respectively. The incidence of for 30- and 90-day heart failure significantly decreased from 19.3% and 20.3% to 8.5% and 9.1%, respectively. We observed significant changes for 30-day atrial fibrillation, whereas the changes over time for 90-day atrial fibrillation and 30- and 90-day stroke/transient ischemic attack remained insignificant. The all-cause mortality within 30- and 90 days significantly decreased over time from 6.7% and 9.2% in 2011 to 1.5% and 2.7% in 2019 and 2016, respectively. In conclusion, this national study provides general insight on the trends of complications and mortality of TAVI, demonstrating significant reductions over time.

Impact of Acute Kidney Injury After Transcatheter Aortic Valve Replacement: A Nationwide Study.

BACKGROUND: In patients undergoing transcatheter aortic valve replacement (TAVR), the impact of acute kidney injury (AKI) on the prognosis and especially on future kidney function has been sparsely examined, and data from large cohorts are warranted. METHODS AND RESULTS: With Danish nationwide registries, we identified all patients undergoing TAVR from 2014 to 2021 with no previous dialysis treatment. According to 2 plasma creatinine samples, we identified those suffering a postprocedural AKI within 21 days after TAVR. With 1 year of follow-up, we compared the associated rates of dialysis treatment and death between patients with and without an AKI using multivariable Cox analysis. Finally, according to the lowest recorded creatinine sample, we assessed the kidney function among AKI survivors between 90 and 180 days after the index date. We identified 4091 TAVRs: 193 (4.7%) with AKI (55.4% men; median age, 82 years) and 3898 (95.3%) without AKI (57.0% men; median age, 81 years). Compared with those without AKI, patients with AKI showed increased associated 1-year rates of dialysis treatment (hazard ratio [HR], 7.20 [95% CI, 4.10-12.66]) and death (HR, 2.39 [95% CI, 1.59-3.58]). After 6 months, 74% of AKI survivors had complete kidney recovery, 14.7% had incomplete kidney recovery, 6.3% failed to recover, and 5.1% were on dialysis treatment. CONCLUSIONS: We identified that AKI after TAVR was associated with an increased rate of future dialysis treatment and all-cause death. Among survivors, 74% had complete kidney recovery within 6 months.

Patient mortality following new-onset heart failure stratified by cancer type and status.

AIM: Expected 1-year survival is essential to risk stratification of patients with heart failure (HF); however, little is known about the 1-year prognosis of patients with HF and cancer. Thus, the objective was to investigate the 1-year prognosis following new-onset HF stratified by cancer status in patients with breast, gastrointestinal, or lung cancer. METHODS AND RESULTS: All Danish patients with new-onset HF from 2000 to 2018 were included. Cancer status was categorized as history of cancer (no cancer-related contact within 5 years of HF diagnosis), non-active cancer (curative intended procedure administered) and active cancer. Standardized 1-year all-cause mortality was reported using G-computation. Age-stratified 1-year all-cause mortality was estimated using the Kaplan-Meier estimator. In total, 193 359 patients with HF were included, 7.3% had either a breast, gastrointestinal, or lung cancer diagnosis. Patients with cancer were older and more comorbid than patients without cancer. Standardized 1-year all-cause mortality (95% confidence intervals) was 24.6% (23.0-26.2%), 27.1% (25.5-28.6%), and 29.9% (25.9-34.0%) for history of breast, gastrointestinal and lung cancer, respectively, which was comparable to patients with non-active cancers. For active breast, gastrointestinal and lung cancer, standardized 1-year all-cause mortality was 36.2% (33.8-38.6%), 49.0% (47.2-50.9%), and 61.6% (59.7-63.5%), respectively. One-year all-cause mortality increased incrementally with age, except for active lung cancer. CONCLUSION: Standardized 1-year all-cause mortality was comparable for patients with history of cancer and non-active cancer regardless of cancer type, but varied comprehensively for active cancers. Prognostic impact of age was limited for active lung cancer. Thus, granular stratification of cancer is necessary for optimized management of new-onset HF.

Patient characteristics and long-term outcomes in patients undergoing transcatheter aortic valve implantation in a failed surgical prosthesis vs in a native valve: A Danish nationwide study.

BACKGROUND: Valve-in-valve-transcatheter aortic valve implantation (TAVI) is a feasible and increasingly used treatment option for failed surgical aortic prosthesis, but data from clinical practice are limited. We aimed to examine patient characteristics and outcomes of patients undergoing TAVI in a surgival valve (valve-in-valve TAVI) compared with patients undergoing TAVI in a native valve. METHODS: Using nationwide registries, we identified all Danish citizens, who underwent TAVI from January 1, 2008, to December 31, 2020. RESULTS: A total of 6,070 patients undergoing TAVI were identified; 247 (4%) patients had a history of SAVR (The valve-in-valve cohort). The median age of the study population was 81 (25th-75th percentile 77-85) and 55% were men. Patients with valve-in-valve-TAVI were younger but had a greater burden of cardiovascular comorbidities compared with patients with native-valve-TAVI. Within 30 days post procedure, 11 (0.2%) and 748 (13.8%) patients who underwent valve-in-valve-TAVI and native-valve-TAVI, respectively, had a pacemaker implantation. The cumulative 30-day risk of death among patients with valve-in-valve-TAVI was 2.4% (95% CI: 1.0%-5.0%) and 2.7% (95% CI: 2.3%-3.1%) in patients with native-valve-TAVI, respectively. Correspondingly, the cumulative 5-year risk of death was 42.5% (95% CI: 34.2%-50.6%) and 44.8% (95% CI: 43.2%-46.4%), respectively. In multivariable Cox proportional hazard analysis, valve-in-valve-TAVI was not associated with a significantly different risk of death at 30 days (Hazard ratio (HR) = 0.95, 95% CI 0.41-2.19) and 5 years (HR = 0.79, 95% CI 0.62-1.00) post-TAVI compared with native-valve-TAVI. CONCLUSIONS: TAVI in a failed surgical aortic prosthesis as compared to TAVI in a native valve, was not associated with significantly different short- and long-term mortality, suggesting that valve-in-valve-TAVI is a safe procedure.

Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Fluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy. OBJECTIVES: The authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM. METHODS: Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95% CIs were reported. RESULTS: Included were 331,189 patients with T2DM: 44.2% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95% CI: 1.78-4.23). CONCLUSIONS: NSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.

Nursing Home Admission Following Transcatheter Aortic Valve Replacement: A Danish Nationwide Cohort Study.

BACKGROUND: Loss of autonomy associated with nursing home admission (NHA) is a concern for patients. Yet the incidence of NHA after transcatheter aortic valve replacement (TAVR) is unknown. OBJECTIVES: The aim of this study was to investigate the incidence and factors associated with NHA following TAVR compared with the general population. METHODS: Through Danish registries, patients alive at discharge after TAVR were identified from January 2014 to October 2021. Patients were matched 1:5 on sex, age, and calendar year to the general population. The 3-year cumulative incidence and 95% CI of NHA were estimated using the Aalen-Johansen estimator, accounting for the competing risk for death. Through multivariate cause-specific Cox regression models, factors associated with NHA were examined. RESULTS: In total, 5,312 TAVR patients were matched to 26,560 control subjects with a median age of 81 years and 56.1% males. Comorbidity burden was higher for TAVR patients. The 3-year cumulative incidence of NHA was 6.3% (95% CI: 5.5%-7.1%) for TAVR patients compared with 5.8% (95% CI: 5.4%-6.1%) for the general population. For TAVR patients >85 years of age, the cumulative incidence of NHA was 11.6% (95% CI: 9.5%-13.8%), and the risk for death was 23.3% (95% CI: 20.4%-26.2%). Factors associated with NHA were increasing age, frailty, living alone, and atrial fibrillation. CONCLUSIONS: TAVR was not associated with an increased incidence of NHA compared with the general population. Despite the increased incidence of NHA for TAVR patients >85 years of age, approximately 2 in 3 patients were still alive and not admitted to nursing homes 3 years after TAVR.

Need for home care or nursing home admission after myocardial infarction complicated by cardiogenic shock and/or out-of-hospital cardiac arrest.

AIMS: Myocardial infarction (MI) with cardiogenic shock (CS) and/or out-of-hospital cardiac arrest (OHCA) are conditions with potential loss of autonomy. In patients with MI, the association between CS and OHCA and need for home care or nursing home admission was examined. METHODS AND RESULTS: Danish nationwide registries identified patients with MI (2008-19), who prior to the event lived at home without home care and discharged alive. One-year cumulative incidences and hazard ratios (HRs) were reported for home care need or nursing home admission, a composite proxy for disability in activities of daily living (ADL), along with all-cause mortality. The study population consisted of 67 109 patients with MI (by groups: -OHCA/-CS: 63 644; -OHCA/+CS: 1776; +OHCA/-CS: 968; and +OHCA/+CS: 721). The 1-year cumulative incidences of home care/nursing home were 7.1% for patients who survived to discharge with -OHCA/-CS, 20.9% for -OHCA/+CS, 5.4% for +OHCA/-CS, and 8.2% for those with +OHCA/+CS. The composite outcome was driven by home care. With the -OHCA/-CS as reference, the adjusted HRs for home care/nursing home were 2.86 (95% CI: 2.57-3.19) for patients with -OHCA/+CS; 1.31 (95% CI: 1.00-1.73) for + OHCA/-CS; and 2.18 (95% CI: 1.68-2.82) for those with +OHCA/+CS. The 1-year cumulative mortality were 5.1% for patients with -OHCA/-CS, 9.8% for -OHCA/+CS, 3.0% for +OHCA/-CS, and 3.4% for those with +OHCA/+CS. CONCLUSION: In patients discharged alive after a MI, CS, and to a lesser degree OHCA were associated with impaired ADL with a two-fold higher 1-year incidence of home care or nursing home admission compared with MI patients without CS or OHCA.

Prognosis of acute coronary syndrome stratified by cancer type and status - a nationwide cohort study.

BACKGROUND: To investigated the prognosis of the most prevalent cancers (breast-, gastrointestinal-, and lung cancer), according to cancer status (i.e., active-, non-active-, history of-, and no cancer), following first-time of acute coronary syndrome (ACS). METHODS: Danish nationwide registers were used to identify patients with first-time ACS from 2000-2018. Patients were stratified according to cancer type and status. Hazard ratios (HR) estimated by adjusted Cox regression models for 1year all-cause mortality reported. Further absolute risks of 1year cardiovascular versus non-cardiovascular death and 30-day cumulative incidence of coronary angiograms (CAG) was estimated, using the Aalen-Johansen non-parametric method, with competing risk of death. RESULTS: We identified 150,478 (95.7%) with no cancer, 2,370 (1.5%) with history of cancer, 2,712 (1.7%) with non-active cancer and 1,704 (1.1%) with active cancer. Cancer patients were older with more comorbidities than patients with no cancer. When compared with no cancer, we found HRs (95% confidence intervals) of 1.71 (1.44-2.02), 2.47 (2.23-2.73) and 4.22 (3.87-4.60) correspondingly for active breast-, gastrointestinal-, and lung cancer. Increased HRs were also found for non-active cancers, but not for history of cancer. Cardiovascular disease was the leading cause of death in all patients. Among patients with active breast-, gastrointestinal-, and lung cancer 43%, 43%, and 31% underwent CAG, correspondingly, compared with 77% of patients without cancer. CONCLUSIONS: Active- and non-active cancers were associated with an increased 1-year all-cause mortality compared with patients with history of cancer and no cancer. Cardiovascular disease was the leading cause of death; notably CAG was less frequently performed in cancer patients.

Mortality at one year after transcatheter aortic valve replacement - Relation of age and comorbidities.

Background: Of patients undergoing transcatheter aortic valve replacement (TAVR), 80-90 % are at extreme, high, or intermediate risk. Patient selection considering futile outcomes in these groups is difficult as significant comorbidity burden is common. Thus, we examined 1-year mortality after TAVR according to age and comorbidities. Methods: Between 2008 and 2021 all Danish TAVR-patients were included. From a multivariate Cox-regression model, significant characteristics associated with 1-year all-cause mortality were identified. The study population was divided into four groups according to number of significant comorbidities present at baseline: Low (0 comorbidities), mild (1 comorbidity), moderate (2 comorbidities), and high (3 or more comorbidities). The 1-year risk of all-cause mortality with 95 % confidence intervals (CI) was estimated by each group. Results: In total, 7,104 patients underwent TAVR. Significant covariates associated with 1-year all-cause mortality were chronic kidney disease, heart failure, chronic obstructive pulmonary disease, peripheral artery disease, and age ≥ 85 years. The four baseline groups comprised low (n = 2,666), mild (n = 2,814), moderate (n = 1,246), and high comorbidity burden (n = 378). The 1-year risk of all-cause mortality was 5.5 % (95 %CI: 4.6-6.4 %) in the low baseline comorbidity burden group. Conversely, the 1-year risk of all-cause mortality was 25.0 % (95 %CI: 20.4-29.3 %) in the high baseline burden group. Conclusions: In a national sample of TAVR patients, readily available information on age and comorbidities, can be used to identify a high-risk group with 25 % 1-year mortality. This provides physicians and patients with an easy-to-understand view on 1-year prognosis after TAVR and may complement patient selection for improved long-term outcomes.

Temporal trends in utilization of transcatheter aortic valve replacement and patient characteristics: A nationwide study.

AIM: To investigate trends in the utilization of transcatheter aortic valve replacement (TAVR) and changes in the characteristics of patients undergoing first-time TAVR. METHODS: Using Danish nationwide registers, we included all patients undergoing TAVR between 2008 and 2020. To compare patient characteristics, the study population was stratified according to calendar year of procedure: 2008-2010, 2011-2013, 2014-2016, and 2017-2020. RESULTS: We identified 6,097 patients undergoing TAVR with year-by-year increases in TAVR penetration rate. Over time, the age of the patients remained stable (2008-2010: median age 82 year [interquartile range (IQR): 77-86] vs 2017-2020: median age 81 years [IQR: 77-85]). Moreover, there was an increase in male patients (2008-2010: 49.9% vs 2017-2020: 57.4%) and patients with diabetes (2008-2010: 14.2% vs 2017-2020: 19.2%). Conversely, a history of stroke (2008-2010: 15.8% vs 2017-2020: 13.1%), previous myocardial infarction (2008-2010: 22.4% vs 2017-2020: 10.0%), heart failure (2008-2010: 40.5% vs 2017-2020: 25.2%), and peripheral artery disease (2008-2010: 14.8% vs 2017-2020: 10.4) decreased among patients. CONCLUSIONS: TAVR utilization increased markedly in the years 2008-2020. Patients undergoing TAVR had less comorbidity over time while age remained stable. Thus, despite expanding to patients at lower surgical risk, TAVR is still offered mainly to older patients.

Bleeding Risk Following Systemic Fluconazole or Topical Azoles in Patients with Atrial Fibrillation on Apixaban, Rivaroxaban, or Dabigatran.

BACKGROUND: Bleeding safety in relation to use of systemic fluconazole and topical azoles among patients with atrial fibrillation treated with apixaban, rivaroxaban, or dabigatran is insufficiently explored, despite clinical relevance and several reports suggesting associations. METHODS: Using nationwide Danish registers, we identified patients with atrial fibrillation initiated on apixaban, rivaroxaban, or dabigatran from 2012-2018. We investigated associations between bleeding incidents and systemic fluconazole or topical azole treatment using a case-crossover design with 30-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We included 32,340 (36%), 32,409 (36%), and 24,940 (28%) patients initiated on apixaban, rivaroxaban, and dabigatran, respectively. Patients on apixaban were older (median age: 77 years; interquartile range [IQR] 70-84) compared with rivaroxaban users (median age: 75 years; IQR 68-82) and patients on dabigatran (median age: 73 years; IQR 66-80). Apixaban users had a significantly increased risk of bleeding following exposure to systemic fluconazole: odds ratio (OR) 3.5; 95% confidence interval (CI), 1.4-10.6. No increased risk was found among rivaroxaban and dabigatran users: ORs of 0.9 (95% CI, 0.2-3.0) and 1.7 (95% CI, 0.5-5.6), respectively. As to bleeding risk pertaining to topical azole exposure among apixaban, rivaroxaban, and dabigatran users, no association was found, with corresponding ORs of 0.8 (95% CI, 0.5-1.3); 1.3 (95% CI, 0.9-2.1); and 1.2 (95% CI 0.8-1.8), respectively. CONCLUSION: In patients with atrial fibrillation on either apixaban, rivaroxaban, or dabigatran, an association between an elevated bleeding risk and use of systemic fluconazole was found among patients on apixaban. We found no increased risk of bleeding following co-exposure to topical azoles.

Testing Denmark: a Danish Nationwide Surveillance Study of COVID-19.

"Testing Denmark" is a national, large-scale, epidemiological surveillance study of SARS-CoV-2 in the Danish population. Between September and October 2020, approximately 1.3 million people (age >15 years) were randomly invited to fill in an electronic questionnaire covering COVID-19 exposures and symptoms. The prevalence of SARS-CoV-2 antibodies was determined by point-of care rapid test (POCT) distributed to participants' home addresses. In total, 318,552 participants (24.5% invitees) completed the study and 2,519 (0.79%) were seropositive. Of the participants with a prior positive PCR test (n = 1,828), 29.1% were seropositive in the POCT. Although seropositivity increased with age, participants 61 years and over reported fewer symptoms and were tested less frequently. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (risk ratio [RR] 7.43, 95% CI: 6.57-8.41), particular in household members (RR 17.70, 95% CI: 15.60-20.10). A greater risk of seropositivity was seen in home care workers (RR 2.09, 95% CI: 1.58-2.78) compared to office workers. A high degree of adherence with national preventive recommendations was reported (e.g., >80% use of face masks), but no difference were found between seropositive and seronegative participants. The seroprevalence result was somewhat hampered by a lower-than-expected performance of the POCT. This is likely due to a low sensitivity of the POCT or problems reading the test results, and the main findings therefore relate to risk associations. More emphasis should be placed on age, occupation, and exposure in local communities. IMPORTANCE To date, including 318,522 participants, this is the largest population-based study with broad national participation where tests and questionnaires have been sent to participants' homes. We found that more emphasis from national and local authorities toward the risk of infection should be placed on age of tested individuals, type of occupation, as well as exposure in local communities and households. To meet the challenge that broad nationwide information can be difficult to gather. This study design sets the stage for a novel way of conducting studies. Additionally, this study design can be used as a supplementary model in future general test strategy for ongoing monitoring of COVID-19 immunity in the population, both from past infection and from vaccination against SARS-CoV-2, however, with attention to the complexity of performing and reading the POCT at home.