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.

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.

Infrequent transition to direct oral anticoagulants in patients with cancer.

INTRODUCTION: Pharmacokinetic drug-drug interactions (DDIs) are challenging aspects of direct oral anticoagulant (DOAC) therapy in patients with cancer. We evaluated the prevalence of potential DOAC/antineoplastic agent DDIs and the one-year cumulative incidence of switching from low-molecular-weight heparin (LMWH) to a DOAC in patients with cancer. METHODS: Patients with cancer and an indication of LMWH were included from Herlev and Gentofte Hospital, Denmark, in the 2014-2019 period. Follow-up was initiated when the first dose of LMWH was dispensed. Data were obtained from electronic medical records. One-year cumulative incidence of switching from LMWH to DOAC was estimated using the Aalen-Johansen estimator. Potential DDIs were evaluated using a report from the European Heart Rhythm Association (EHRA) and a review by Hellfritzsch et al. RESULTS. A total of 161 patients were included with a median age of 70.8 (interquartile range: 64.2-76.1) years. The one-year cumulative incidence of switching from LMWH to DOAC was 32% (95% confidence intervals: 21-43%) in patients eligible for DOACs. Using the EHRA report, a total of 24% of antineoplastic agents were not identified. This percentage decreased to 8% using data from Hellfritzsch et al. CONCLUSIONS. In patients with cancer, the one-year cumulative incidence of switching from LMWH to DOAC was less-t 35% in patients eligible for DOAC, revealing a potential for improved anticoagulant treatment. Furthermore, contemporary data elaborated on potential DDIs between DOACs/antineoplastic agents. FUNDING: "Helsefonden" (21-B-0350) and the "Karen Elise Jensens Fonden" (29-4-2021) funded the study. TRIAL REGISTRATION: Not relevant.

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.

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.

Risk of Worsening Heart Failure and All-Cause Mortality Following COVID-19 Vaccination in Patients With Heart Failure: A Nationwide Real-World Safety Study.

BACKGROUND: Patients with heart failure are vulnerable to the SARS-CoV-2 infection. However, limited evidence exists on the safety of the SARS-CoV-2 mRNA vaccines in this patient population. The objective of this study was to investigate the risk of all-cause mortality, worsening heart failure, venous thromboembolism, and myocarditis associated with the mRNA vaccines in patients with heart failure. METHODS: Using Danish nationwide registries, 2 cohorts were constructed: (1) all prevalent heart failure patients in 2019 aged 40 to 95 years and (2) all prevalent heart failure patients in 2021 aged 40 to 95 years, who were vaccinated with either of the 2 mRNA vaccines (BNT162B2 or mRNA-1273). The patients in the 2 cohorts were matched 1:1 using exact exposure matching on age, sex, and duration of heart failure. To estimate standardized absolute risks, outcome-specific Cox regression analyses were performed. RESULTS: The total study population comprised 101 786 patients. The median age of the study population was 74 years (interquartile range, 66-81). The standardized risk of all-cause mortality within 90 days was 2.23% (95% CI, 2.10%-2.36%) in the vaccinated cohort and 2.56% (95% CI, 2.43%-2.70%) in the unvaccinated cohort (90-day risk difference, -0.33% [95% CI, -0.52% to -0.15%]). The standardized risk of worsening heart failure within 90 days was 1.10% (95% CI, -1.01% to 1.19%) in the 2021 (vaccinated) cohort and 1.08% (95% CI, 0.99%-1.17%) in the 2019 (unvaccinated) cohort (risk difference, 0.02% [95% CI, -0.11% to 0.15%]). No significant differences were found regarding venous thromboembolism or myocarditis. CONCLUSIONS: Receiving an mRNA vaccine was not associated with an increased risk of worsening heart failure, myocarditis, venous thromboembolism, or all-cause mortality.

Frailty and Recurrent Hospitalization After Transcatheter Aortic Valve Replacement.

Background For frail patients with limited life expectancy, time in hospital following transcatheter aortic valve replacement is an important measure of quality of life; however, data remain scarce. Thus, we aimed to investigate frailty and its relation to time in hospital during the first year after transcatheter aortic valve replacement. Methods and Results From 2008 to 2020, all Danish patients who underwent transcatheter aortic valve replacement and were alive at discharge were included. Using the validated Hospital Frailty Risk Score, patients were categorized in the low, intermediate, and high frailty groups. Time in hospital and mortality up to 1 year are reported according to frailty groups. In total, 3437 (57.6%), 2277 (38.1%), and 257 (4.3%) were categorized in the low, intermediate, and high frailty groups, respectively. Median age was ≈81 years. Female sex and comorbidity burden were incrementally higher across frailty groups (low frailty: heart failure, 24.1%; stroke, 7.2%; and chronic kidney disease, 4.5%; versus high frailty: heart failure, 42.8%; stroke, 34.2%; and chronic kidney disease, 29.2%). In the low frailty group, 50.5% survived 1 year without a hospital admission, 10.8% were hospitalized >15 days, and 5.8% of patients died. By contrast, 26.1% of patients in the high frailty group survived 1 year without a hospital admission, 26.4% were hospitalized >15 days, and 15.6% died within 1 year. Differences persisted in models adjusted for sex, age, frailty, and comorbidity burden (excluding overlapping comorbidities). Conclusions Among patients undergoing transcatheter aortic valve replacement, frailty is strongly associated with time in hospital and mortality. Prevention strategies for frail patients to reduce hospitalization burden could be beneficial.

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.

Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study.

AIMS: In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls. METHODS AND RESULTS: Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD. CONCLUSION: Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors.

Seasonal influenza vaccine uptake among patients with cardiovascular disease in Denmark, 2017-2019.

BACKGROUND: Influenza vaccination protects against morbidity and mortality in patients with cardiovascular disease (CVD). We aimed to describe influenza vaccine uptake in patients with CVD in a universal-access healthcare system. METHODS: Using nationwide Danish registries, we included all patients with prevalent CVD, defined as heart failure (HF), atrial fibrillation (AF), ischemic heart disease (IHD), or stroke during three consecutive influenza seasons (October-December 2017-2019). The outcome was relative frequency of influenza vaccination across strata of patient characteristics. RESULTS: There was an average of 397 346 patients with CVD yearly during 2017-2019. Vaccine uptake was 45.6% for the whole population and ranged from 55.0% in AF to 61.8% in HF among patients aged ≥65 years. Among patients aged <65 years, uptake was 32.6% in HF, 19.0% in AF, 21.1% in IHD, and 18.3% in stroke. There was a lower uptake with decreasing age: 21.6% in HF, 5.5% in AF, 7.4% in IHD, and 6.3% in stroke among males aged <45 years, as opposed to 25.5% in HF, 11.5% in AF, 13.8% in IHD, and 12.1% in stroke for males aged 45-54 years. In the further stratified analyses, uptake ranged from a low of 2.5% for males <45 years with AF who were not vaccinated the previous season to a high of 87.0% for females ≥75 years with IHD who were vaccinated the previous season. CONCLUSION: Seasonal influenza vaccine uptake is suboptimal among patients with CVD, even in a universal-access healthcare system with free-of-charge vaccinations. Vaccine uptake was particularly low among young 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.

"No one told me anything about it and I cannot explain it": Illness perception in symptomatic and asymptomatic patients with cancer-associated thrombosis.

INTRODUCTION: Patients with cancer, have reported cancer-associated thrombosis (CAT), a distressing event in their overall illness. However, whether the clinical presentation of CAT; symptomatic versus asymptomatic, impacts illness perception is poorly elucidated. The aim of this study was to explore illness perception in patients with CAT, stratified by the clinical presentation. MATERIALS AND METHODS: In a qualitative design, we conducted a three-step workshop. Patients were included from a specialised cardiology care unit for oncology patients. Data analysis was performed using framework analysis. The analytic framework was based on the five components of illness perception: (1) identity of illness, (2) causal beliefs, (3) timeline beliefs, (4) beliefs about control/cure and (5) consequences. RESULTS: Elleven patients with CAT participated in the workshop; five symptomatic and six asymptomatic. Whitin each category of illness perception following notions emerged (1) the identity of CAT was only tangible for symptomatic participants, (2) the aetiology was considered important information for symptomatic participants, which was in contrast to asymptomatic participants, (3) asymptomatic participant did not consider recurrent CAT a threat towards their health, (4) asymptomatic participants were prone to information overload, whilst information was imperative to the sense of control in symptomatic participants, (5) low molecular weight heparin treatment was accepted in symptomatic participants due to remission of symptoms. CONCLUSIONS: The clinical presentation of CAT (asymptomatic/symptomatic) proved essential to illness perception. These findings indicate that information level and communication within the medical consultation, should actively consider the clinical presentation of CAT in order to optimize management and compliance.

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.

Discontinuation of direct oral anticoagulants among patients with atrial fibrillation according to gender and cohabitation status: a nationwide cohort study.

AIMS: The aim of this study was to evaluate the risk of discontinuing treatment with direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF) according to cohabitation status and gender. METHODS AND RESULTS: Using the Danish national registers, we identified 32 364 patients with AF aged 40-90 years undergoing treatment with DOACs. The study period was from 2013 to 2017, and patients were followed for 2 years, or until death, outcome, or emigration. The main outcome was discontinuation of DOAC treatment for at least 30 days. The absolute 2-year risk of DOAC discontinuation was highest among men living alone [35.7%, 95% confidence interval (CI): 37.3-34.1%]. Men living alone had a 4.6% (95% CI: 6.4-2.8%) higher absolute risk of discontinuation and a 12% [hazard ratio (HR): 1.12, 95% CI: 1.04-1.20] higher relative risk of discontinuation compared with men living with a partner. Female patients living alone likewise had a higher absolute risk of DOAC discontinuation (2.6%, 95% CI: 4.4-0.09%) compared with female patients living with a partner, yet no statistically significant difference in relative risk. In an analysis evaluating gender, we found male gender to be associated with a significantly higher relative risk of DOAC discontinuation (HR: 1.33, 95% CI: 1.26-1.40) compared with female gender (P-value for interaction with cohabitant status = 0.5996). CONCLUSION: In this nationwide population study, male gender and living alone were associated with a higher risk of DOAC discontinuation among patients with AF.

Outcomes of prolonged dual anti-platelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A nationwide registry-based study.

BACKGROUND: Randomized controlled trials have shown a reduced risk of ischemic events and an increased risk of bleeding in patients treated with prolonged dual anti-platelet therapy (DAPT) beyond 12 months following acute coronary syndrome (ACS). We aimed to investigate outcomes of prolonged DAPT vs aspirin monotherapy (ASA) in a real-world population. METHODS AND RESULTS: Using nationwide registries, we identified all patients with ACS who underwent percutaneous coronary intervention and received 12-month DAPT between January 2013 and October 2016. Patients still on DAPT were compared to patients on ASA at index date (15 months after ACS-date) and followed for up to 2 years. Cox regression models were employed to calculate standardized risks of all-cause mortality, major adverse cardiovascular event (MACE), and major bleeding. The study included 7,449 patients, 1,901 on DAPT (median age 66, 72.1% male) and 5,548 on ASA (median age 65, 75.1% male). Standardized absolute 2-year risk of all-cause mortality, MACE, and major bleeding was 2.7%, 3.7%, and 5.4% for DAPT vs 2.2%, 3.8%, and 1.3% for ASA. DAPT was not associated with a significant standardized 2-year risk difference (SRD) of all-cause mortality (SRD: 0.5%, 95% confidence interval [CI]: -0.9 to 1.7) or MACE (SRD: -0.1%, 95% CI -1.8 to 1.6), but a significantly higher risk of major bleeding (SRD: 4.1%, 95% CI 1.8-6.6). CONCLUSIONS: In a nationwide cohort of ACS patients undergoing percutaneous coronary intervention, prolonged DAPT was not significantly associated with a reduced risk of all-cause mortality or MACE, but an increased risk of major bleeding. Future randomized controlled trials should investigate the optimal anti-platelet regimen in this patient group.

All-cause mortality, stroke, and bleeding in patients with atrial fibrillation and valvular heart disease.

AIMS: To compare the risk of all-cause mortality, stroke, and bleeding in patients with atrial fibrillation (AF) and valvular heart disease (VHD) treated with vitamin K antagonist (VKA) or factor Xa-inhibitors (FXa-I; rivaroxaban and apixaban). METHODS AND RESULTS: We cross-linked data from Danish nationwide registries identifying patients with AF and VHD (aortic stenosis/insufficiency, mitral insufficiency, bioprosthetic heart valves, mitral-, and aortic valve repair) initiating VKA or FXa-I between January 2014 and June 2017. Outcomes were all-cause mortality, stroke, and bleeding. Using cause-specific Cox regression, we reported the standardized absolute 2-year risk of the outcomes and absolute risk differences (ARD). We identified 1115 (41.7%), 620 (23.1%), and 942 (35.2%) patients initiating treatment with VKA, rivaroxaban, and apixaban, respectively. The standardized absolute risk (95% confidence interval) of all-cause mortality associated with VKA treatment was 34.1% (30.4-37.8%) with corresponding ARD for FXa-I of -2.7% (-6.7% to 1.4%). The standardized absolute risk of stroke for VKA was 3.8% (2.2-5.4%) with corresponding ARD for FXa-I of -0.1% (-2.0% to 1.8%). The standardized risk of bleeding for VKA was 10.4% (7.2-12.9%) with corresponding ARD for FXa-I of -2.0% (-5.1% to 1.1%). The risk of bleeding was significantly reduced in subgroup analyses of apixaban compared with VKA [ARD: -3.9% (-7.0% to -0.9%)] and rivaroxaban [ARD: -5.6% (-9.5% to -1.7%)]. CONCLUSION: In this nationwide cohort study, there were no significant differences in the risks of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with VKA compared with FXa-I.

Risk of gastrointestinal bleeding associated with oral anticoagulation and non-steroidal anti-inflammatory drugs in patients with atrial fibrillation: a nationwide study.

AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs. METHODS AND RESULTS: Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64-78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04-0.18%) for NOACs and 0.13% (0.03-0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69-0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40-2.61)] and with VKA [HR 1.95 (95% CI 1.21-2.69)]. CONCLUSION: Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.

Dose reduction of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A Danish nationwide cohort study.

INTRODUCTION: To investigate the patterns of dose reduction of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF). MATERIALS AND METHODS: Using Danish nationwide registries, we identified all non-valvular AF patients initiated on standard-dose NOAC during 2011-2017 who were followed until dose reduction. The absolute risk of dose reduction was presented as cumulative incidence both overall and according to baseline characteristics. Moreover, to assess baseline comorbidities related to dose reduction, adjusted Cox regression models were used. In subgroup analysis, we investigated dose reduction following acute myocardial infarction and/or percutaneous coronary intervention (MI/PCI), chronic kidney disease (CKD), turned 80 years, intracranial hemorrhage, peripheral bleeding, ischemic stroke, cancer, bone fracture, and antiplatelet treatment start. RESULTS: Of 24,489 patients included, 12.2% experienced dose reduction during the study period. Dabigatran treatment, higher age at inclusion, high CHA2DS2-VASc score, and high HAS-BLED score were related to higher risk of dose reduction. Baseline ischemic heart disease (IHD), heart failure, cancer, CKD, chronic obstructive pulmonale disease (COPD), and hypertension were independent predictors of dose reduction. In subgroup analysis with six-month follow-up, MI/PCI, CKD, intracranial hemorrhage, peripheral bleeding, and antiplatelet treatment therapy were strongly associated with dose reduction. CONCLUSIONS: Dose reduction of NOACs was observed in 12.2% of AF patients during 2011-2017 and was associated with dabigatran treatment, advanced age at baseline, high CHA2DS2-VASc score, and high HAS-BLED score. Among comorbidities, IHD, heart failure, cancer, CKD, COPD, and hypertension predicted dose reduction independently. During six-month follow-up, MI/PCI showed the strongest association with dose reduction.