Effect of low climate impact vs. high climate impact inhalers for patients with asthma and COPD-a nationwide cohort analysis

Asthma; Climate impact; PneumoniaAsma; Impacte climàtic; PneumòniaAsma; Impacto climático; NeumoníaBackground Chronic obstructive pulmonary disease (COPD) and asthma can be treated with inhaled corticosteroids (ICS) delivered by low climate impact inhalers (dry powder inhalers) or high climate impact inhalers (pressurized metered-dose inhalers containing potent greenhouse gasses). ICS delivered with greenhouse gasses is prescribed ubiquitously and frequent despite limited evidence of superior effect. Our aim was to examine the beneficial and harmful events of ICS delivered by low and high climate impact inhalers in patients with asthma and COPD. Methods Nationwide retrospective cohort study of Danish outpatients with asthma and COPD treated with ICS delivered by low and high climate impact inhalers. Patients were propensity score matched by the following variables; age, gender, tobacco exposure, exacerbations, dyspnoea, body mass index, pulmonary function, ICS dose and entry year. The primary outcome was a composite of hospitalisation with exacerbations and all-cause mortality analysed by Cox proportional hazards regression. Results Of the 10,947 patients with asthma and COPD who collected ICS by low or high climate impact inhalers, 2,535 + 2,535 patients were propensity score matched to form the population for the primary analysis. We found no association between high climate impact inhalers and risk of exacerbations requiring hospitalization and all-cause mortality (HR 1.02, CI 0.92–1.12, p = 0.77), nor on pneumonia, exacerbations requiring hospitalization, all-cause mortality, or all-cause admissions. Delivery with high climate impact inhalers was associated with a slightly increased risk of exacerbations not requiring hospitalization (HR 1.10, CI 1.01–1.21, p = 0.03). Even with low lung function there was no sign of a superior effect of high climate impact inhalers. Conclusion Low climate impact inhalers were not inferior to high climate impact inhalers for any risk analysed in patients with asthma and COPD.This study was funded by the Novo Nordisk Foundation (No. NNF20OC0060657). Open access funding provided by Copenhagen Universit

Left atrial functional measurements' utility in predicting long-term risk of atrial fibrillation after isolated CABG

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia following coronary artery bypass grafting (CABG). We hypothesized that measures of left atrial (LA) function would be useful in predicting AF in patients undergoing CABG.METHODS AND RESULTS: In the study, 611 patients were included after CABG. All patients had echocardiograms performed preoperatively and LA functional measurements were assessed. These measurements were LA maximum volume index (LAVmax), LA minimum volume index (LAVmin) and LA emptying fraction (LAEF). The endpoint was AF occurring &gt;14 days after surgery. During the follow-up period of a median of 3.7 years, 52 (9%) developed AF. The mean age was 67 years, 84% were male and the average left ventricle ejection fraction was 50%. Patients who developed AF had a lower CCS class and lower LAEF (40 vs. 45%), otherwise no clinical differences were observed between outcome groups. No functional LA measurements were significant predictors of AF in the whole CABG population. However, in patients with normal-sized LA (n = 532, events: 49), both LAEF and LAVmin were univariable predictors of AF. When the functional measurements were adjusted for the CHADS2 score, both LAVmin (HR = 1.07 [1.01-1.13], p = .014) and LAEF (HR: 1.02 [1.00-1.03], p = .023), remained significant predictors.CONCLUSION: No echocardiographic measurements were significant predictors of AF after CABG. In patients with a normal LA size, LAVmin as well as LAEF were significant predictors of AF.</p

AM/PM dosing of LAMA for COPD: a randomized controlled trial protocol using digital recruitment and registries

Rationale: Long-acting muscarinic antagonists (LAMAs) reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), usually taken once daily in the morning. However, the circadian activity of autonomic regulation suggests that the highest need for anticholinergic therapy may be in the late night/early morning. This is supported by evidence that AECOPD most often begins in the morning. Furthermore, the trough spirometry effect of LAMA is lower than the peak effect, which further argues that evening dosing may be more optimal than morning dosing. This trial aims to determine whether evening administration of LAMA reduces hospitalization-requiring AECOPD or death from all causes within 1 year as compared to morning administration of the same LAMA. Methods: Randomized controlled open-label trial. Persons aged 30 years or older with a once-daily LAMA prescription and a confirmed COPD diagnosis were recruited. Participants were randomized in a 1:1 ratio to either morning or evening LAMA administration. Complete follow-up for the primary outcome, hospitalization-requiring AECOPD, or death from all causes within 1 year was captured from the Danish National Health Register, as were patient-reported outcome assessments at 6 and 12 months. Results: A total of 10,013 participants were randomized, and the recruitment process started on 9 March 2023. Secondary outcomes include (i) moderate COPD exacerbations; (ii) all-cause hospitalization; (iii) ICU admission; (iv) need for non-invasive ventilation; and (v) all-cause mortality, among others. All outcomes will be evaluated 12 months after recruitment. Clinical trial registration:ClinicalTrials.gov, NCT05563675

Flu Vaccine and Mortality in Hypertension:A Nationwide Cohort Study

BACKGROUND: Influenza infection may increase the risk of stroke and acute myocardial infarction (AMI). Whether influenza vaccination may reduce mortality in patients with hypertension is currently unknown. METHODS AND RESULTS: We performed a nationwide cohort study including all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007 to 2016 who were prescribed at least 2 different classes of antihypertensive medication (renin‐angiotensin system inhibitors, diuretics, calcium antagonists, or beta‐blockers). We excluded patients who were aged 100 years, had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer, or cerebrovascular disease. The exposure to influenza vaccination was assessed before each influenza season. The end points were defined as death from all‐causes, from cardiovascular causes, or from stroke or AMI. For each influenza season, patients were followed from December 1 until April 1 the next year. We included a total of 608 452 patients. The median follow‐up was 5 seasons (interquartile range, 2–8 seasons) resulting in a total follow‐up time of 975 902 person‐years. Vaccine coverage ranged from 26% to 36% during the study seasons. During follow‐up 21 571 patients died of all‐causes (3.5%), 12 270 patients died of cardiovascular causes (2.0%), and 3846 patients died of AMI/stroke (0.6%). After adjusting for confounders, vaccination was significantly associated with reduced risks of all‐cause death (HR, 0.82; P<0.001), cardiovascular death (HR, 0.84; P<0.001), and death from AMI/stroke (HR, 0.90; P=0.017). CONCLUSIONS: Influenza vaccination was significantly associated with reduced risks of death from all‐causes, cardiovascular causes, and AMI/stroke in patients with hypertension. Influenza vaccination might improve outcome in hypertension

Heart failure associated with imported malaria:a nationwide Danish cohort study

Abstract Aims Despite adequate treatment, recent studies have hypothesized that malaria may affect long‐term cardiovascular function. We aimed to investigate the long‐term risk of cardiovascular events and death in individuals with a history of imported malaria in Denmark. Methods Using nationwide Danish registries, we followed individuals with a history of malaria for the risk of incident heart failure (HF), myocardial infarction (MI), cardiovascular death and all‐cause death (1 January 1994 to 1 January 2017). The population was age‐ and sex‐matched with individuals without a history of malaria from the Danish population (ratio 1:9). We excluded patients with known HF and ischaemic heart disease at inclusion. Results We identified 3912 cases with a history of malaria (mean age 33 ± 17 years, 57% male, 41% Plasmodium falciparum infections). The median follow‐up was 9.8 years (interquartile range 3.9–16.4 years). Event rates per 1000 person‐years for individuals with a history vs. no history of malaria were HF: 1.84 vs. 1.32; MI: 1.28 vs. 1.30; cardiovascular death: 1.40 vs. 1.77; and all‐cause death: 5.04 vs. 5.28. In Cox proportional hazards models adjusted for cardiovascular risk factors, concomitant pharmacotherapy, region of origin, household income and educational level, malaria was associated with HF (HR: 1.59 [1.21–2.09], P = 0.001), but not MI (HR: 1.00 [0.72–1.39], P = 1.00), cardiovascular death (HR: 1.00 [0.74–1.35], P = 0.98) or all‐cause death (HR 1.11 [0.94–1.30], P = 0.21). Specifically, P. falciparum infection was associated with increased risk of HF (HR: 1.64 [1.14–2.36], P = 0.008). Conclusion Individuals with a history of imported malaria, specifically P. falciparum, may have an increased risk of incident HF

Calcium Channel Blockers and the Risk of Exacerbation in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Study of 48,488 Outpatients

Patients with chronic obstructive pulmonary disease (COPD) are prone to developing arterial hypertension, and many patients are treated with the calcium channel blocker amlodipine. However, it remains unclear whether using this drug potentially affects the risk of acute severe exacerbations (AECOPD) and all-cause mortality in these patients. The data were collected from Danish national registries, containing complete information on health, prescriptions, hospital admissions, and outpatient clinic visits. The COPD patients (n = 48,488) were matched via propensity score on known predictors of the primary outcome in an active comparator design. One group was exposed to amlodipine treatment, and the other was exposed to bendroflumethiazide, since both of these drugs are considered to be the first choice for the treatment of arterial hypertension according to Danish guidelines. The use of amlodipine was associated with a reduced risk of death from all causes at the 1-year follow-up (hazard ratio 0.69, 95% confidence interval: 0.62–0.76) compared with the use of bendroflumethiazide in the matched patients. No difference in the risk of severe AECOPD was found. In the COPD patients, amlodipine use was associated with a lower risk of death from all causes compared with the use of bendroflumethiazide. Amlodipine seems to be a safe first choice for the treatment of arterial hypertension in COPD patients.publishedVersio

Electronic Nudge Letters to Increase Influenza Vaccination Uptake in Younger and Middle-Aged Individuals With Diabetes

BackgroundDespite evidence demonstrating that influenza vaccination is associated with reduced risk of cardiovascular events and all-cause mortality in individuals with diabetes mellitus (DM), vaccine uptake remains suboptimal.ObjectivesThe purpose of this study was to assess the effectiveness of electronically delivered nudges on influenza vaccine uptake according to the presence of DM status versus other chronic diseases.MethodsNUDGE-FLU-CHRONIC was a nationwide, randomized, pragmatic implementation trial among younger and middle-aged (18-64 years) Danish citizens with chronic disease during the 2023/2024 influenza season. Participants were randomized in a 2.45:1:1:1:1:1:1 ratio to usual care (no electronic letter) or 1 of 6 different electronic nudge letters. The endpoint was receipt of a seasonal influenza vaccine on or before January 1, 2024.ResultsOf 299,881 participants, 57,666 (19.2%) had DM (median age: 51.6 years, 43.0% female). During the season, 43.0% of those with DM vs 34.6% of those without DM received the vaccine (P &lt; 0.001). Any electronic letter vs usual care was highly effective in increasing vaccine uptake in participants with DM (45.6% vs 36.5%, difference: +9.1 percentage points [99.29% CI: 7.9-10.3], relative risk ratio: 1.42 [99.29% CI: 1.39-1.44]). However, DM status modified the effect of the interventions such that participants without DM at baseline experienced a greater relative gain than those with DM (37.3% vs 25.9%, difference: +12.3 percentage points [99.29% CI: 11.7-12.8], risk ratio: 1.47 [99.29% CI: 1.45-1.50]; Pinteraction&lt;0.001).ConclusionsElectronic nudge letters effectively boosted vaccine uptake in individuals with DM and in individuals free of DM but with other chronic diseases, but the effect was lower among those with DM. Electronic nudges represent a low-cost and effective strategy to boost influenza vaccination rates in the DM population. (Nationwide Utilization of Danish Government Electronic Letter System for Increasing InFLUenza Vaccine Uptake Among Adults With Chronic Disease; NCT06030739

Time of day for vaccination, outcomes, and relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine: a post-hoc analysis of the DANFLU-1 randomized clinical trial

Objectives Morning influenza vaccination enhances antibody response. In this posthoc analysis of the DANFLU-1 trial, we sought to evaluate the association between time of day for vaccination (ToV) and outcomes, and whether ToV modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccine. Methods DANFLU-1 was a pragmatic feasibility trial of QIV-HD vs. QIV-SD. Outcomes included hospitalizations and mortality. For subgroup analysis, the population was dichotomized at median ToV into two groups (early and late). Results The study population included 12,477 participants. Mean age was 71.7±3.9 years with 5,877 (47.1%) female participants. Median ToV was 11.29AM. Earlier ToV was associated with fewer respiratory hospitalizations independent of vaccine type, which persisted in adjusted analysis (IRR 0.88 per 1-hour decrement (95% CI 0.78- 0.98, p=0.025). No effect modification by continuous or dichotomous ToV was found. In subgroup analysis, effects consistently favored QIV-HD against hospitalizations for pneumonia or influenza (early: IRR 0.30; late: 0.29), all-cause hospitalizations (early: IRR 0.87; late: 0.86), and mortality (early: HR 0.53; late: 0.50). Conclusion In this exploratory post-hoc analysis, earlier ToV was associated with fewer respiratory hospitalizations. The relative effectiveness of QIV-HD vs. QIV-SD was not modified by ToV. Further research is needed to confirm findings. Trial Registration Clinicaltrials.gov: NCT0504858