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.

N-terminal pro-B-type natriuretic peptide levels pre-transcatheter aortic valve implantation and relationship with long-term outcomes.

Background: Blood levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been suggested as a future guidance tool for the selection of patients for aortic valve replacement. This study aimed to examine how levels of NT-proBNP pre-transcatheter aortic valve implantation (TAVI) is associated with one-year rates of heart failure (HF) admission and mortality following TAVI. Methods: With Danish nationwide registries, we identified all patients undergoing TAVI from 2014 to 2021 who had at least one recorded NT-pro-BNP measurement within one year before TAVI. Patients were compared by quartiles of pre-TAVI NT-proBNP: quartile 4 (high NT-proBNP group) vs quartile 1-3 (low NT-proBNP group). Comparisons of all-cause mortality and HF-admissions were conducted using Kaplan-Meier analysis, cumulative incidence, and Cox analysis, as appropriate. Results: We identified 1,140 patients undergoing first-time TAVI with a recorded NT-pro-BNP; 846 (74.2 %) with a low NT-proBNP (<420 pmol/L) (55.0 % male, median age 81 year) and 294 (25.8 %) with a high NT-proBNP (≥420 pmol/L) (53.1 % male, median age 82 year). A high versus low NT-proBNP was associated with increased one-year cumulative incidence of HF-admissions (9.1 % vs. 23.1 %, adjusted HR 2.00 [95 % CI, 1.40-2.85]) and all-cause mortality (6.0 % vs. 14.6 %, adjusted HR 1.95 [95 % CI: 1.24-3.07]). A high NT-proBNP was associated with higher rates of outcomes irrespective of previously known atrial fibrillation, HF, chronic kidney disease, and hypertension. Conclusion: In patients undergoing TAVI, a baseline NT-proBNP ≥ 420 pmol/L was associated with increased one-year rates of HF-admission and mortality post-TAVI and may be utilized to identify a high-risk population.

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.

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.

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.

Surgery in patients with infective endocarditis and prognostic importance of patient frailty.

PURPOSE: Surgery is required in 20-50% of patients with infective endocarditis (IE). Frailty increases surgical risk; however, the prognostic implications of frailty in patients undergoing IE-related surgery remain poorly understood. We aimed to assess the association between frailty and all-cause mortality or rehospitalization after discharge (≥ 14 days). METHODS: We identified all IE patients who underwent surgery during admission (2010-2020) in Denmark. The Hospital Frailty Risk Score was used to categorize patients into two frailty risk groups, patients with low frailty scores (< 5 points) and frail patients (≥ 5 points). We analyzed time hospitalized after discharge and all-cause mortality from the date of surgery with a one-year follow-up. Statistical analyses utilized the Kaplan-Meier estimator, Aalen-Johansen estimator, and the Cox regression model. RESULTS: We identified 1282 patients who underwent surgery during admission, of whom 967 (75.4%) had low frailty scores, and 315 (24.6%) were frail. Frail patients were characterized by advanced age, a lower proportion of males, and a higher burden of comorbidities. Frail patients were more hospitalized (> 14 days) in the first post-discharge year (19.1% vs.12.3%) compared to patients with low frailty scores. Additionally, frail patients had higher rates of all-cause mortality including in-hospital deaths (27% vs. 15%) and rehospitalizations (43.5% vs 26.1%) compared to patients with low frailty scores. This was also evident in the adjusted analysis (hazard ratio 1.36 [CI 95% 1.09-1.71]). CONCLUSION: Frailty was associated with an ≈40% increased rate of rehospitalization (≥ 14 days) or death. Further studies are needed to assess the effectiveness of surgery with a focus on frailty to improve prognostic outcomes in these patients.

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.

High-risk admission prior to transcatheter aortic valve replacement and subsequent outcomes.

BACKGROUND: Severe, symptomatic aortic stenosis may cause heart failure, acute myocardial infarction, or syncope; limited data exist on the occurrence of such events before transcatheter aortic valve replacement (TAVR) and their impact on subsequent outcomes. Thus, we investigated the association between a preceding event and outcomes after TAVR. METHODS: From 2014 to 2021 all Danish patients who underwent TAVR were included. Preceding events up to 180 days before TAVR were identified. A preceding event was defined as a hospitalization for heart failure, acute myocardial infarction, or syncope. The 1-year risk of all-cause death, and cardiovascular or all-cause hospitalization was compared for patients with versus without a preceding event using Kaplan-Meier, Aalen-Johansen, and in Cox regression analyses adjusted for patient characteristics. RESULTS: Of 5,851 patients included, 759 (13.0%) had a preceding event. The median age was 81 years in both groups. Male sex and frailty were more prevalent in patients with a preceding event (males: 64.7% vs 55.2%, frailty: 49.6% vs 40.6%). The most common type of preceding event was a hospitalization for heart failure (n = 524). For patients with a preceding event, the 1-year risk of death was 11.7% (95% CI: 9.4%-14.1%) versus 8.0% (95% CI: 7.2%-8.7%) for patients without. The corresponding adjusted hazard ratio (aHR) was 1.29 (95%CI: 1.01-1.64). Mortality was highest for patients with a preceding event of a heart failure admission (1-year risk: 13.5% [95%CI: 10.5%-16.5%]). Comparing patients with a preceding event to those without, the 1-year risk for cardiovascular rehospitalization was 15.0% versus 8.2% (aHR 1.60 [95%CI: 1.29-1.99]) and 57.6% versus 50.6% for all-cause rehospitalization (aHR 1.08 [95%CI: 0.87-1.20]). CONCLUSIONS: A hospitalization for heart failure, myocardial infarction, or syncope prior to TAVR was associated with a poorer prognosis and could represent a group to focus resource management on. Interventions to prevent preceding events and improvements in pre- and post-TAVR optimization of these patients are warranted.

Sex differences in infective endocarditis: a Danish nationwide study.

PURPOSE: Sex differences in infective endocarditis (IE) are reported, but patient characteristics are sparse and conflicting findings on the association between sex and short-term outcomes demand further research. We aimed to characterize sex differences in IE in terms of patient characteristics, frailty, microbiology, socioeconomic status, management and outcome on a nationwide scale. METHODS: Between 2010 and 2020, we used Danish national registries to characterize patients with IE according to sex using ICD codes and microbiological lab reports. Frailty was assessed with the Hospital Frailty Risk Score. Mortality was reported with Kaplan-Meier estimates. Logistic regression and Cox regression were used for adjusted analyses. RESULTS: We included 6259 patients with IE with 2047 (32.7%) female patients and 4212 (67.3%) male patients. Female patients were older (median age 75.0 years (64.3-82.2) vs. 71.7 (61.7-78.9)) and more frail (Intermediate frailty: 36.5% vs. 33.1%, High frailty: 11.4% vs. 9.2%). Staphylococcus aureus-IE were most common in both sexes (34.6% vs. 28.8%), but fewer female patients had Enterococcus-IE (10.5% vs. 18.1%). Female patients were less surgically treated (14.0% vs. 21.2%). Female sex was associated with increased in-hospital mortality (adj. OR 1.33, 95% CI 1.16-1.52), but no statistically significant difference in associated 1- and 5-year mortality from hospital discharge were identified (adj. HR 1.09, 95% CI 0.95-1.24 and 1.02, 95% CI 0.92-1.12, respectively). CONCLUSION: Female sex is associated with increased in-hospital mortality, but not in long-term mortality as compared with male patients. Female patients have a lower prevalence of Enterococcus-IE and rates of surgery. Further research is needed to understand these differences.

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.

Short- and Long-Term Mortality for Patients With and Without a Cancer Diagnosis Following Pulmonary Embolism in Denmark, 2000 to 2020: A Nationwide Study.

BACKGROUND: New treatment regimens have been introduced in the past 20 years, which may influence the short- and long-term prognosis for patients with and without a cancer diagnosis following pulmonary embolism. However, newer studies investigating these trends are lacking. Therefore, we aimed to investigate the 30- and 31- to 365-day mortality following pulmonary embolism. METHODS AND RESULTS: Using the Danish nationwide registries, patients with a diagnosis of pulmonary embolism between 2000 and 2020 were included. Age- and sex-standardized 30- and 31- to 365-day mortality was calculated and stratified by cancer status. In total, 60 614 patients (29.6% with recent cancer; mean age, 68.2 years) were included. The 30-day mortality for patients with no recent cancer decreased from 19.1% (95% CI, 17.9%-20.4%) in 2000 to 7.3% (95% CI, 6.7%-8.0%) in 2018 to 2020 (hazard ratio [HR], 0.36 [95% CI, 0.32-0.40]; P<0.001). The 30-day mortality for patients with recent cancer decreased from 32.2% (95% CI, 28.8%-36.6%) to 14.1% (95% CI, 12.7%-15.5%) (HR, 0.38 [95% CI, 0.33-0.44]; P<0.001). The 31- to 365-day mortality for patients with no recent cancer decreased from 12.5% (95% CI, 11.4%-13.6%) to 9.4% (95% CI, 8.6%-10.2%) (HR, 0.73 [95% CI, 0.64-0.83]; P<0.001).The 31- to 365-day mortality for patients with recent cancer remained stable: 39.4% (95% CI, 35.1%-43.7%) to 38.3% (95% CI, 35.9%-40.6%) (HR, 0.97 [95% CI, 0.84-1.12]; P=0.69). CONCLUSIONS: From 2000 to 2020, improvements were observed in 30-day mortality following pulmonary embolism regardless of cancer status. For patients with recent cancer, 31- to 365-day mortality did not improve, whereas a minor improvement was observed for patients without recent cancer.

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study.

BACKGROUND: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. METHODS: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. FINDINGS: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. INTERPRETATION: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. FUNDING: Department of Cardiology, Herlev and Gentofte University Hospital. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Temporal Trends in Noncardiovascular Morbidity and Mortality Following Acute Myocardial Infarction.

BACKGROUND: Due to improved management, diagnosis, and care of myocardial infarction (MI), patients may now survive long enough to increasingly develop serious noncardiovascular conditions. OBJECTIVES: This study aimed to test this hypothesis by investigating the temporal trends in noncardiovascular morbidity and mortality following MI. METHODS: We conducted a registry-based nationwide cohort study of all Danish patients with MI during 2000 to 2017. Outcomes were cardiovascular and noncardiovascular mortality, incident cancer, incident renal disease, and severe infectious disease. RESULTS: From 2000 to 2017, 136,293 consecutive patients were identified (63.2% men, median age 69 years). The 1-year risk of cardiovascular mortality between 2000 to 2002 and 2015 to 2017 decreased from 18.4% to 7.6%, whereas noncardiovascular mortality decreased from 5.8% to 5.0%. This corresponded to an increase in the proportion of total 1-year mortality attributed to noncardiovascular causes from 24.1% to 39.5%. Furthermore, increases in 1-year risk of incident cancer (1.9%-2.4%), incident renal disease (1.0%-1.6%), and infectious disease (5.5%-9.1%) were observed (all P trend <0.01). In analyses standardized for changes in patient characteristics, the increased risk of cancer in 2015 to 2017 compared with 2000 to 2002 was no longer significant (standardized risk ratios for cancer: 0.99 [95% CI: 0.91-1.07]; renal disease: 1.28 [95% CI: 1.15-1.41]; infectious disease: 1.28 [95% CI: 1.23-1.34]). CONCLUSIONS: Although cardiovascular mortality following MI improved substantially during 2000 to 2017, the risk of noncardiovascular morbidity increased. Moreover, noncardiovascular causes constitute an increasing proportion of post-MI mortality. These findings suggest that further attention on noncardiovascular outcomes is warranted in guidelines and clinical practice and should be considered in the design of future clinical trials.

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.

High risk of rehospitalization within one year following a pulmonary embolism-Insights from the Danish nationwide registries from 2000-2020.

AIM: To identify the absolute risk, causes and factors associated with rehospitalization within 1 year of discharge with a pulmonary embolism (PE). METHODS AND RESULTS: Using the Danish nationwide registries, all patients admitted with a first-time PE between 2000 and 2020 and discharged alive were included. Subsequent hospitalizations were categorized and crude cumulative incidences, were used to estimate the absolute risk (AR) of any rehospitalization and specific causes of rehospitalizations. Risk factors for rehospitalization were investigated using cause specific Cox regression models.A total of 55 201 patients were identified. The median age of the study population was 70 years (inter quartile range: 59;79), and the most prevalent comorbidities were cancer (29.3%) and ischemic heart disease (12.7%). The 1-year AR of any rehospitalization after discharge with a PE was 48.6% (95% confidence interval (CI); 48.2%-48.8%). The most common cause for being rehospitalized was due to respiratory disease (1-year AR: 9.5% (95% CI: 9.3%-9.8%)), followed by cardiovascular disease (1-year AR: 6.3% (95% CI: 5.9%-6.5%)), cancer (1-year AR: 6.0% (95% CI: 5.8%-6.4%)), venous thromboembolism (1-year AR: 5.2% (95% CI: 5.0%-5.2%)), and symptom diagnoses (1-year AR: 5.2% (95%CI: 5.0%-5.4%)). Factors that were associated with an increased risk of rehospitalization were cancer, liver disease, chronic obstructive pulmonary disease, chronic kidney disease, and immobilization. CONCLUSION: Patients with PE have a high risk of rehospitalization, with almost half of patients being rehospitalized within 1 year. Identification of high-risk patients may help target interventions aiming at reducing the risk of rehospitalization.

Impact of first-time detected atrial fibrillation after transcatheter aortic valve replacement: A nationwide study.

Background: The prognostic implications of new-onset atrial fibrillation (AF) in conjunction with transcatheter aortic valve replacement (TAVR) is sparsely examined. Therefore, we aimed to examine the impact of first-time detected AF after TAVR on all-cause mortality and heart failure (HF). Methods: With Danish nationwide data from 2008 to 2021, we identified all patients who underwent TAVR and were alive 30 days after discharge (index date). Patients were categorized into i) no AF; ii) history of AF; and iii) first-time detected AF within 30 days after discharge. From the index date, two-year rates of all-cause mortality and HF admissions were compared using multivariable adjusted Cox analysis. Results: We identified 6,807 patients surviving 30 days beyond TAVR: 4,229 (62.1%) without AF (55% male, median age 81), 2,283 (33.6%) with history of AF (58% male, median age 82), and 291 (4.3%) with first-time detected AF (56% male, median age 81). Compared with patients without AF, adjusted analysis yielded increased associated hazard ratio (HR) of all-cause mortality in patients with history of AF (1.53 [95% confidence interval [CI], 1.32-1.77]) and in patients with first-time detected AF (2.06 (95%CI, 1.55-2.73]). Further, we observed increased associated HRs of HF admissions in patients with history of AF (1.70 [95%CI, 1.45-1.99]) and in patients with first-time detected AF (1.77 [95%CI, 1.25-2.50]). Conclusion: In TAVR patients surviving 30 days beyond discharge, first-time detected AF appeared to be at least as strongly associated with two-year rates of all-cause mortality and HF admissions, as compared with patients with history of AF.