Outcomes of management strategies in patients with prior coronary artery bypass grafting presenting with an acute coronary syndrome.

BACKGROUND: Patients with prior coronary artery bypass grafting (CABG) presenting with an acute coronary syndrome (ACS) have poor outcomes and the optimal treatment strategy for this population is unknown. METHODS: Using linked administrative databases, we examined patients with an ACS between 2008 and 2019, identifying patients with prior CABG. Patients were categorized by ACS presentation type and treatment strategy. Our primary outcome was the composite of death and recurrent myocardial infarction at one year. RESULTS: Of 54,641 patients who presented with an ACS, 1670 (3.1%) had a history of prior CABG. Of those, 11.0% presented with an ST-elevation myocardial infarction (STEMI) of which, 15.3% were treated medically, 31.1% underwent angiography but were treated medically, 22.4% with fibrinolytic therapy and 31.1% with primary PCI. The primary outcome rate was the highest (36.8%) in patients who did not undergo angiography and was similar in the primary PCI (20.8%) and fibrinolytic group (21.9%). In patients presenting with a non-ST elevation acute coronary syndrome (NSTE-ACS) (89.0%), 33.2% were treated medically, 38.5% underwent angiography but were treated medically and 28.2% were treated with PCI. Compared to those who underwent PCI, patients treated conservatively demonstrated a higher risk of the composite outcome (14.8% vs 27.3%; adjusted hazard ratio 1.70, 95% confidence interval 1.22-2.37). CONCLUSIONS: Patients with prior CABG presenting with an ACS are often treated conservatively without PCI, which is associated with a higher risk of adverse events.

Relationships Between Measures of the Physical Activity-Related Built Environment and Excess Weight in Preschoolers: A Retrospective, Population-Level Cohort Study.

Background: The built environment can impact health outcomes. Our purpose was to examine relationships between built environment variables related to physical activity and excess weight in preschoolers. Methods: In this retrospective, population-level study of 4- to 6-year-olds, anthropometric measurements were taken between 2009 and 2017 in Calgary and Edmonton, Alberta, Canada. Based on BMI z-scores (BMIz), children were classified as normal weight (-2 ≤ BMIz <1) or excess weight (BMIz ≥1; overweight and obesity). Physical activity-related built environment variables were calculated (distances to nearest playground, major park, school; street intersection density; number of playgrounds and major parks within an 800 m buffer zone). Binomial logistic regression models estimated associations between physical activity-related built environment variables and excess weight. Results: Our analysis included 140,368 participants (females: n = 69,454; Calgary: n = 84,101). For Calgary, adjusted odds ratios (aORs) showed the odds of excess weight increased 1% for every 100-intersection increase [1.010 (1.006-1.015); p < 0.0001] and 13.6% when there were ≥4 playgrounds (vs. 0 or 1) within an 800 m buffer zone [1.136 (1.037-1.243); p = 0.0059]. For Edmonton, aORs revealed lower odds of excess weight for every 100 m increase in distances between residences to nearest major park [0.991 (0.986-0.996); p = 0.0005] and school [0.992 (0.990-0.995); p < 0.0001]. The odds of excess weight decreased as the number of major parks within the 800 m buffer zone increased from 0 to 1 [0.943 (0.896-0.992); p = 0.023] and from 0 to ≥3 [0.879 (0.773-0.999); p = 0.048]. Conclusion: The physical activity-related built environment was associated with excess weight in preschoolers, although relationships varied between cities that differed demographically and geographically.

Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium/glucose cotransporter 2 inhibitors (SGLT2i) are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2i uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart failure clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2i use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2i. Utilization of SGLT2i increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2i use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2i use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95% CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95% CI 0.54-0.77). However, SGLT2i usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2i in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2i and improve implementation.

Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

BACKGROUND: Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. METHODS: All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 µg/L, or ferritin concentration between 100 and 300 µg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. RESULTS: Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. CONCLUSIONS: Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and Women Without Diabetes at Baseline: A Population-Based Study of 608 474 Adults.

BACKGROUND: We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline. METHODS AND RESULTS: This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3-year enrollment period. The primary outcome of CVD hospitalization and secondary outcome of combined CVD hospitalization/mortality were examined during a 5-year follow-up period until March 31, 2021. A total of 608 474 individuals (55.2% women) were included. Compared with HbA1c 5.0% to 5.4%, men with HbA1c of 5.5% to 5.9% had an increased risk of CVD hospitalization (adjusted hazard ratio [aHR], 1.12 [95% CI, 1.07-1.19]) whereas women did not (aHR, 1.01 [95% CI, 0.95-1.08]). Men and women with HbA1c of 6.0% to 6.4% had a 38% and 17% higher risk and men and women with HbA1c ≥6.5% had a 79% and 51% higher risk of CVD hospitalization, respectively. In addition, HbA1c of 6.0% to 6.4% and HbA1c ≥6.5% were associated with a higher risk (14% and 41%, respectively) of CVD hospitalization/death in men, but HbA1c ≥6.5% was associated with a 24% higher risk only among women. CONCLUSIONS: In both men and women, HbA1c ≥6.0% was associated with an increased risk of CVD and mortality outcomes. The association between CVD and HbA1c levels of 5.5% to 5.9%, considered to be in the "normal" range, highlights the importance of optimizing cardiovascular risk profiles at all levels of glycemia, especially in men.

Sex Differences in High-Cost Users of Healthcare for Atrial Fibrillation.

Background: Healthcare resource use for atrial fibrillation (AF) is high, but it may not be equivalent across all patients. We examined whether sex differences exist for AF high-cost users (HCUs), who account for the top 10% of total acute care costs. Methods: All patients aged ≥ 20 years who presented to the emergency department (ED) or were hospitalized with AF were identified in Alberta, Canada, between 2011 and 2015. The cohort was categorized by sex into HCUs and non-HCUs. Healthcare utilization was defined as ED, hospital, and physician visits, and costs included those for hospitalization, ambulatory care, physician billing, and drugs. All costs were inflated to 2022 Canadian dollars (CAD$). Results: Among 48,030 AF patients, 45.1% were female. Of these, 31.8% were HCUs, and the proportions of female and male patients were equal (31.9% vs 31.7%). Female HCUs were older, more likely to have hypertension and heart failure, and had a higher stroke risk than male HCUs. Mean healthcare utilization did not differ among HCUs by sex, except for number of ED visits, which was higher in male patients (12.7% vs 9.2%, P < 0.0001). Overall, HCUs accounted for 65.8% of the total costs (CAD$3.4 billion). Almost half of total HCU costs were attributable to female HCUs (CAD$966.1 million). Significant differences were present in the distributions of HCU-related costs (male patients: 74.6% hospitalization, 9.5% ambulatory care, 12.4% physician billing, 3.5% drugs; female patients: 77.7% hospitalization, 7.4% ambulatory care, 11.5% physician billing, 3.5% drugs, P < 0.0001). Conclusions: Despite having a lower AF prevalence, female patients represent an equal proportion of HCUs, and account for almost half the total HCU costs. Interventions targeted at reducing the number of AF HCU are needed, particularly for female patients.

Contexte: L'utilisation des ressources en santé est élevée pour la fibrillation auriculaire (FA), mais elle n'est pas forcément équivalente pour tous les patients. Nous avons examiné s'il existait des différences entre les sexes pour ce qui est des cas très coûteux de FA, qui représentent les 10 % supérieurs des coûts totaux de soins de courte durée. Méthodologie: Tous les patients âgés de 20 ans et plus qui se sont présentés au service des urgences ou qui ont été hospitalisés pour une FA ont été répertoriés en Alberta, au Canada, entre 2011 et 2015. La cohorte a été divisée par sexe en fonction des utilisateurs très coûteux et des autres utilisateurs. L'utilisation des soins de santé était définie comme des consultations aux urgences, à l'hôpital ou chez le médecin, et les coûts comprenaient les hospitalisations, les soins ambulatoires, les honoraires des médecins et les médicaments. Tous les coûts ont été convertis en dollars canadiens ($ CA) de 2022. Résultats: Parmi les 48 030 patients atteints de FA, 45,1 % étaient des femmes et 31,8 % étaient des utilisateurs très coûteux, en proportions égales entre les femmes et les hommes (31,9 % vs 31,7 %). Parmi les utilisateurs très coûteux, les femmes étaient plus âgées, plus susceptibles de présenter de l'hypertension et une insuffisance cardiaque, et leur risque d'AVC était plus élevé comparativement aux hommes. L'utilisation moyenne des soins de santé n'affichait pas de différences chez les utilisateurs très coûteux selon le sexe, à l'exception des consultations aux urgences, qui étaient plus fréquentes chez les hommes (12,7 % vs 9,2 %, p < 0,0001). Dans l'ensemble, les utilisateurs très coûteux représentaient 65,8 % des coûts totaux, qui étaient de 3,4 milliards de dollars canadiens. Les femmes représentaient par ailleurs près de la moitié du total des utilisations très coûteuses (966,1 millions de dollars canadiens). Des différences significatives ont été observées quant à la répartition des coûts liés aux utilisateurs très coûteux (hommes : hospitalisations [74,6 %], soins ambulatoires [9,5 %], honoraires des médecins [12,4 %], médicaments [3,5 %]; femmes : hospitalisations [77,7 %], soins ambulatoires [7,4 %], honoraires des médecins [11,5 %], médicaments [3,5 %], p < 0,0001). Conclusions: Bien que la FA soit moins fréquente chez les femmes que chez les hommes, celles-ci représentent une proportion tout aussi importante des utilisations très coûteuses et comptent pour presque la moitié des coûts totaux attribuables aux utilisateurs très coûteux. Des interventions visant à réduire les utilisations très coûteuses pour la FA sont donc nécessaires, particulièrement chez les femmes.

Lower Socioeconomic Status is Associated with an Increased Incidence and Spectrum of Major Congenital Heart Disease and Associated Extracardiac Pathology.

Several studies have suggested an inverse relationship between lower socioeconomic status (SES) and the incidence of congenital heart disease (CHD) among live births. We sought to examine this relationship further in a Canada-wide population study, exploring CHD subtypes, trends, and associated noncardiac abnormalities. Infants born in Canada (less Quebec) from 2008 to 2018 with CHD requiring intervention in the first year were identified using ICD-10 codes through the Canadian Institute for Health Information Discharge Abstract Database. Births of CHD patients were stratified by SES (census-based income quintiles) and compared against national birth proportions using X2 tests. Proportions with extracardiac defects (ED) and nonlethal genetic syndromes (GS) were also explored. From 2008 to 2018, 7711 infants born with CHD were included. The proportions of major CHD distributed across SES quintiles were 27.1%, 20.1%, 19.2%, 18.6%, and 15.0% from lowest to highest, with significant differences relative to national birth proportions (22.0%, 20.0%, 20.6%, 20.7%, and 16.7% from lowest (1) to highest (5)) (p < 0.0001). No temporal trends in the CHD proportions across SES categories were observed over the study period. The distribution across SES quintiles was different only for specific CHD subtypes (double-outlet right ventricle (n = 485, p = 0.03), hypoplastic left heart syndrome (n = 547, p = 0.006), heterotaxy (n = 224, p = 0.03), tetralogy of Fallot (n = 1007, p = 0.008), truncus arteriosus (n = 126, p < 0.0001), and ventricular septal defect (n = 1916, p < 0.0001)), with highest proportions observed in the lowest quintile. The proportion of the total population with ED but not GS was highest in lower SES quintiles (< 0.0001) commensurate with increased proportion of CHD. Our study suggests a negative association between SES and certain CHD lesions and ED.

The Challenges of Identifying Patients With Peripheral Artery Disease Utilizing Administrative Databases.

Peripheral artery disease (PAD) carries a high burden of morbidity when identified in patients with coronary artery disease (CAD). However, identification of patients with concomitant CAD and PAD remains challenging. Using linked administrative databases of 207,026 individuals with CAD between 2002 and 2019 (median follow-up, 4.7 years), a model for PAD was applied to identify baseline PAD and the development of PAD during follow-up. Both baseline PAD and future PAD models demonstrated poor calibration and discrimination (c-statistic 0.618 and 0.583). In the absence of additional variables, the present models are unable to identify patients with concomitant CAD and PAD.

La maladie artérielle périphérique (MAP) impose un lourd fardeau de morbidité lorsqu'elle est diagnostiquée chez les patients atteints de coronaropathie. Toutefois, il reste difficile de repérer les patients atteints à la fois de coronaropathie et de MAP. À partir de bases de données administratives liées comptant 207 026 personnes atteintes de coronaropathie entre 2002 et 2019 (suivi médian de 4,7 ans), un modèle pour la MAP a été appliqué afin de repérer une MAP initiale et l'apparition d'une MAP au cours du suivi. Les modèles de MAP initiale et de MAP future ont tous deux été associés à un calibrage et à une capacité de distinction insatisfaisants (statistique C de 0,618 et 0,583). En l'absence d'autres variables, les modèles actuels sont incapables de repérer les patients atteints de coronaropathie et de MAP concomitantes.

Associations between social determinants of health and weight status in preschool children: a population-based study. / Associations entre les déterminants sociaux de la santé et le statut pondéral des enfants d'âge préscolaire : une étude de population.

INTRODUCTION: Social determinants of health (SDH) may influence children's weight status. Our objective was to examine relationships between SDH and preschoolers' weight status. METHODS: This retrospective cohort study included 169 465 children (aged 4-6 years) with anthropometric measurements taken at immunization visits from 2009 to 2017 in Edmonton and Calgary, Canada. Children were categorized by weight status based on WHO criteria. Maternal data were linked to child data. The Pampalon Material and Social Deprivation Indexes were used to assess deprivation. We used multinomial logistic regression to generate relative risk ratios (RRRs) to examine associations between ethnicity, maternal immigrant status, neighbourhood-level household income, urban/ rural residence and material and social deprivation with child weight status. RESULTS: Children of Chinese ethnicity were less likely than those in the General Population to have overweight (RRR = 0.64, 95% CI: 0.61-0.69) and obesity (RRR = 0.51, 0.42-0.62). Children of South Asian ethnicity were more likely than those in the General Population to have underweight (RRR = 4.14, 3.54-4.84) and more likely to have obesity (RRR = 1.39, 1.22-1.60). Children with maternal immigrant status were less likely than those without maternal immigrant status to have underweight (RRR = 0.72, 0.63-0.82) and obesity (RRR = 0.71, 0.66-0.77). Children were less likely to have overweight (RRR = 0.95, 0.94-0.95) and obesity (RRR = 0.88, 0.86-0.90) for every CAD 10 000 increase in income. Relative to the least deprived quintile, children in the most materially deprived quintile were more likely to have underweight (RRR = 1.36, 1.13-1.62), overweight (RRR = 1.52, 1.46-1.58) and obesity (RRR = 2.83, 2.54-3.15). Relative to the least deprived quintile, children in the most socially deprived quintile were more likely to have overweight (RRR = 1.21, 1.17-1.26) and obesity (RRR = 1.40, 1.26-1.56). All results are significant to p < 0.001. CONCLUSION: Our findings suggest the need for interventions and policies to address SDH in preschoolers to optimize their weight and health.

Use of Guideline-Directed Medical Therapy in Patients Aged ≥ 65 Years After the Diagnosis of Heart Failure: A Canadian Population-Based Study.

Background: Guideline-directed medical therapy (GDMT) improves clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Despite its proven efficacy, GDMT is underutilized in clinical practice. The current study examines GDMT utilization after incident hospitalization for HF to promote medication initiation, and titration to target dosing within a reasonable time period. Methods: This observational study identified 66,372 patients with HFrEF who were aged ≥ 65 years and had an incident HF hospitalization, using administrative health data (2013-2018). GDMT (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, ß-blockers (BB), and mineralocorticoid receptor antagonists ) received within the 6 months after hospitalization was evaluated by monitoring therapy combinations, optimal dosing (proportion receiving ≥ 50% of the target dose for these inhibitors and blockers, and any dose of MRA), and maximal and last dose assessed, and by use of a GDMT intensity score. Results: Among patients with HFrEF, 4768 (7.2%) were on no therapy, 17,184 (25.9%), were on monotherapy, 30,912 (46.6%) were on dual therapy, and 13,508 (20.4%) were on triple therapy. Only 8747 (13.2%) and 5484 (8.3%) achieved optimal GDMT based on the maximum dose and the last dispensed dose, respectively, within 6 months postdischarge. Finally, 38,869 (58.6%) achieved < 50% of the maximum intensity score, 23,006 (34.7%) achieved between 50% and 74% of the maximum intensity score, and 4497 (6.8%) achieved a score that was ≥ 75% of the maximum intensity score. Conclusions: Current pharmacologic management for patients with HFrEF does not align with the Canadian guidelines. Given this gap in care, innovative strategies to optimize care in patients with HFrEF are needed.

Introduction: Les traitements médicamenteux préconisés dans les lignes directrices (TMPLD) permettent d'améliorer les résultats cliniques des patients atteints d'insuffisance cardiaque à fraction d'éjection réduite (ICFER). En dépit des preuves de leur efficacité, les TMPLD sont sous-utilisés dans la pratique clinique. La présente étude porte sur l'utilisation des TMPLD après une hospitalisation incidente en raison d'une IC afin de favoriser l'amorce de la médication, et l'ajustement de la posologie en vue d'atteindre la dose cible dans un délai raisonnable. Méthodes: Cette étude observationnelle portait sur 66 372 patients atteints d'ICFER qui avaient ≥ 65 ans et une hospitalisation incidente en raison d'une IC, et reposait sur les données administratives sur la santé (2013-2018). Nous avons évalué les TMPLD (inhibiteurs de l'enzyme de conversion de l'angiotensine, bloqueurs des récepteurs de l'angiotensine, ß-bloquants [BB] et antagonistes des récepteurs des minéralocorticoïdes [ARM]) reçus dans les six mois après l'hospitalisation par la surveillance des combinaisons de traitement, la posologie optimale (proportion recevant ≥ 50 % de la dose cible pour ces inhibiteurs et ces bloquants, et toute dose d'ARM), la dose maximale et la dernière dose évaluées, et par l'utilisation d'un score d'intensité des TMPLD. Résultats: Parmi les patients atteints d'ICFER, 4 768 (7,2 %) n'avaient reçu aucun traitement, 17 184 (25,9 %), avaient reçu une monothérapie, 30 912 (46,6 %) avaient reçu une bithérapie et 13 508 (20,4 %) avaient reçu une trithérapie. Seuls 8 747 (13,2 %) et 5 484 (8,3 %) avaient obtenu les TMPLD optimaux en fonction de la dose maximale et de la dernière dose administrée, et ce, respectivement, dans les six mois après la sortie de l'hôpital. Enfin, 38 869 (58,6 %) avaient obtenu < 50 % du score d'intensité maximale, 23 006 (34,7 %) avaient obtenu entre 50 % et 74 % du score d'intensité maximale, et 4 497 (6,8 %) avaient obtenu un score qui était ≥ 75 % du score d'intensité maximale. Conclusions: La prise en charge pharmacologique actuelle des patients atteints d'ICFER va à l'encontre des lignes directrices canadiennes. Compte tenu de cette lacune dans les soins, des stratégies novatrices pour optimiser les soins aux patients atteints d'ICFER sont nécessaires.

Impact of Socioeconomic Status and Residence Distance on Infant Heart Disease Outcomes in Canada.

Background Socioeconomic status (SES) impacts clinical outcomes associated with severe congenital heart disease (sCHD). We examined the impact of SES and remoteness of residence (RoR) on congenital heart disease (CHD) outcomes in Canada, a jurisdiction with universal health insurance. Methods and Results All infants born in Canada (excluding Quebec) from 2008 to 2018 and hospitalized with CHD requiring intervention in the first year were identified. Neighborhood level SES income quintiles were calculated, and RoR was categorized as residing <100 km, 100 to 299 km, or >300 km from the closest of 7 cardiac surgical programs. In-hospital mortality at <1 year was the primary outcome, adjusted for preterm birth, low birth weight, and extracardiac pathology. Among 7711 infants, 4485 (58.2%) had moderate CHD (mCHD) and 3226 (41.8%) had sCHD. Overall mortality rate was 10.5%, with higher rates in sCHD than mCHD (13.3% versus 8.5%, respectively). More CHD infants were in the lowest compared with the highest SES category (27.1% versus 15.0%, respectively). The distribution of CHD across RoR categories was 52.3%, 21.3%, and 26.4% for <100 km, 100 to 299 km, and >300 km, respectively. Although SES and RoR had no impact on sCHD mortality, infants with mCHD living >300 km had a higher risk of mortality relative to those living <100 km (adjusted odds ratio [aOR], 1.43 [95% CI, 1.11-1.84]). Infants with mCHD within the lowest SES quintile and living farthest away had the highest risk for mortality (aOR, 1.74 [95% CI, 1.08-2.81]). Conclusions In Canada, neither RoR nor SES had an impact on outcomes of infants with sCHD. Greater RoR, however, may contribute to higher risk of mortality among infants with mCHD.

Nationwide Study of Sex Differences in Incident Heart Failure in Newly Diagnosed Nonvalvular Atrial Fibrillation.

Background: Heart failure (HF) is a leading complication of nonvalvular atrial fibrillation (NVAF), and the presence of both conditions worsens prognosis. Sex-specific associations between NVAF and outcomes focus on stroke; less is known about HF. We evaluated sex differences in incident HF in NVAF. Methods: We identified adults age ≥ 65 years hospitalized for incident NVAF without prior HF from April 2010 to March 2018 in Canada. The primary outcome was incident HF hospitalization, with a secondary composite outcome of incident HF hospitalization or all-cause mortality at 1 year. Cox proportional hazard regression models were constructed for the association between sex and outcomes, adjusting for age, comorbidities, socioeconomic status, cardioversion, and medications. Results: Of 68,909 NVAF patients, 53.8% were women. Women had a higher rate of the primary outcome (30.0% vs 25.6%, P < 0.001) and the composite outcome (39.5% vs 36.6%, P < 0.001) than men. In multivariable analysis without adjusting for medications, there was an 8% increase risk of HF (95% confidence interval [CI] 1.05-1.11, P < 0.001) for women, which was attenuated when accounting for medication (hazard ratio [HR] 1.01, 95% CI 0.98-1.04). After full adjustment, women age ≥ 75 years were at higher risk of the primary outcome (HR 1.10, 95% CI 1.06-1.13, P < 0.001) and the composite outcome (HR 1.04, 95% CI 1.01-1.07, P < 0.001), compared with men, whereas there was a significantly lower risk for those age 65-75 years. Conclusions: In this nationwide study of incident NVAF without HF, women age ≥ 75 years were more likely to develop HF or die than men. Strategies to prevent HF in older women with NVAF are needed.

Contexte: L'insuffisance cardiaque (IC) est une complication majeure de la fibrillation auriculaire non valvulaire (FANV), et la présence des deux affections assombrit le pronostic. Les associations entre la FANV et ses complications en fonction du sexe ont surtout porté sur l'AVC; on en connaît moins sur l'IC. Nous avons évalué les différences entre les sexes pour l'IC fortuite dans la FANV. Méthodologie: Nous avons identifié des adultes de ≥ 65 ans, sans antécédents d'IC, hospitalisés pour une FANV fortuite entre avril 2010 et mars 2018 au Canada. L'hospitalisation à la suite d'une IC fortuite constituait le critère d'évaluation principal, le critère d'évaluation secondaire composé comprenait les hospitalisations pour un épisode d'IC fortuite ou le décès toutes causes confondues à un an. Des modèles de régression à risques proportionnels de Cox ont servi à évaluer l'association entre le sexe et les résultats, après correction en fonction de l'âge, des comorbidités, de la situation socio-économique, de la cardioversion et de la médication. Résultats: Le groupe étudié comptait 68 909 patients atteints de FANV dont 53,8 % étaient des femmes. Les femmes étaient plus nombreuses à répondre au critère d'évaluation principal (30,0 % vs 25,6 %, p < 0,001) et au critère d'évaluation composé (39,5 % vs 36,6 %, p < 0,001). Dans une analyse multivariée ne comportant aucune correction en fonction de la médication, une augmentation de 8 % du risque d'IC (intervalle de confiance [IC] à 95 % : 1,05-1,11, p < 0,001) a été notée chez les femmes. Cette augmentation se trouvait atténuée lorsque la médication était prise en compte (rapport des risques instantanés [RRI] : 1,01, IC à 95 % : 0,98-1,04). Après correction complète, les femmes de ≥ 75 ans ont été associées à un risque plus élevé d'atteindre le critère d'évaluation principal (RRI : 1,10, IC à 95 % : 1,06-1,13, p < 0,001) et le critère d'évaluation composé (RRI : 1,04, IC à 95 % : 1,01-1,07, p < 0,001) comparativement aux hommes; en revanche, le risque était significativement plus faible chez les femmes de 65-75 ans. Conclusions: Dans cette étude nationale sur la FANV fortuite sans IC, les femmes de ≥ 75 ans étaient plus susceptibles de développer une IC ou de décéder que les hommes d'où la nécessité de mettre en place des stratégies de prévention de l'IC chez les femmes plus âgées atteintes de FANV.

Trends in Uptake and Adherence to Oral Anticoagulation for Patients With Incident Atrial Fibrillation at High Stroke Risk Across Health Care Settings.

Background Oral anticoagulation (OAC) therapy prevents morbidity and mortality in nonvalvular atrial fibrillation; whether location of diagnosis influences OAC uptake or adherence is unknown. Methods and Results Retrospective cohort study (2008-2019), identifying adults with incident nonvalvular atrial fibrillation across health care settings (emergency department, hospital, outpatient) at high risk of stroke. OAC uptake and adherence via proportion of days covered for direct OACs and time in therapeutic range for warfarin were measured. Proportion of days covered was categorized as low (0-39%), intermediate (40-79%), and high (80-100%). Warfarin control was defined as time in therapeutic range ≥65%. All-cause mortality was examined at a 3-year landmark. Among 75 389 patients with nonvalvular atrial fibrillation (47.0% women, mean 77.4 years), 19.7% were diagnosed in the emergency department, 59.1% in the hospital, and 21.2% in the outpatient setting. Ninety-day OAC uptake was 51.6% in the emergency department, 50.9% in the hospital, and 67.9% in the outpatient setting (P<0.0001). High direct OAC adherence increased from 64.9% to 80.3% in the emergency department, 64.3% to 81.7% in the hospital, and 70.9% to 88.6% in the outpatient setting over time (P values for trend <0.0001). Warfarin control was 40.3% overall and remained unchanged. In multivariable analysis, outpatient diagnosis compared with the hospital was associated with greater OAC uptake (odds ratio [OR], 1.79; [95% CI, 1.72-1.87]) and direct OAC (OR, 1.42; [95% CI, 1.27-1.59]) and warfarin (OR, 1.49; [95% CI, 1.36-1.63]) adherence. Varying or persistently low adherence was associated with a poor prognosis, especially for warfarin. Conclusions Locale of nonvalvular atrial fibrillation diagnosis is associated with varying OAC uptake and adherence. Interventions specific to health care settings are needed to improve stroke prevention.

Epidemiology of Worsening Heart Failure in a Population-based Cohort from Alberta, Canada: Evaluating Eligibility for Treatment With Vericiguat.

BACKGROUND: Patients with heart failure (HF) and a reduced ejection fraction (HFrEF) who experience worsening HF (WHF) events are at increased risk of adverse outcomes and experience significant morbidity and mortality. We herein describe the epidemiology of these patients and identify those potentially eligible for vericiguat therapy in this population-based study. METHODS AND RESULTS: This retrospective cohort study included hospitalized or emergency department patients with a primary diagnosis of HF and a left ventricular ejection fraction (LVEF) of less than 45% diagnosed between April 1, 2009, and March 31, 2019 in Alberta, Canada, with follow-up to March 31, 2020. Inclusion criteria from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection (VICTORIA) trial were applied to explore eligibility for vericiguat. Among 25,629 patients with HF and LVEF data, 9948 (38.8%) had HFrEF, of which 5259 (52.8%) experienced WHF at some point during a median 5.8 years of follow-up, and 38.3% of those met the vericiguat trial eligibility criteria. Compared with patients with HFrEF without WHF, those with WHF were older, with more comorbidities, worse renal function, and similar LVEF status, but greater use of HF medications at baseline. At the time of WHF, 27% of those with HFrEF and WHF were on triple therapy, 50.6% were on dual therapy, and 15.4% were on monotherapy. All-cause mortality and the composite outcome of all-cause mortality or cardiovascular hospitalization at 1-year of follow-up were higher in the HFrEF with WHF cohort compared with HFrEF without WHF (adjusted hazard ratios of 1.92 and 1.51, respectively, both P < .0001). CONCLUSIONS: Approximately one-half of patients with HFrEF experienced WHF over the long-term follow-up. Most were not on triple therapy, highlighting the underuse of the existing standard-of-care treatments and opportunities for application of newer therapies; more than one-third of patients with HFrEF may be eligible for vericiguat. LAY SUMMARY: Among patients with heart failure (HF), those who experience worsening HF (WHF) are at increased risk of adverse outcomes. A few new therapies, including vericiguat, have emerged recently for patients with HF and reduced ejection fraction. However, the epidemiology, treatment patterns, and outcomes of patients with WHF in large representative populations is unclear. In the current study, approximately one-half of the patients with HF and reduced ejection fraction experienced WHF and 38.3% were potentially eligible for vericiguat therapy. The guideline-recommended therapies were under-utilized among patients with WHF, which highlights the need for initiatives to address this care gap.

Sex Differences in the Management of Oral Anticoagulation and Outcomes for Emergency Department Presentation of Incident Atrial Fibrillation.

STUDY OBJECTIVE: To examine sex differences in oral anticoagulation management and outcomes among patients with incident nonvalvular atrial fibrillation presenting to the emergency department (ED). METHODS: We identified patients older than 20 years presenting to the ED with incident nonvalvular atrial fibrillation between April 1, 2012, and March 30, 2019, using linked administrative databases in Alberta, Canada. We assessed the use of and adherence to oral anticoagulants at 1 year using the proportion of days covered for direct oral anticoagulants and time in therapeutic range for warfarin. Outcomes included stroke, heart failure, and all-cause mortality at 1 year. RESULTS: Of the 28,886 patients with nonvalvular atrial fibrillation presenting to ED, 44% were females. After adjustment, the rate of oral anticoagulant use was 5% lower in females with a guideline indication than that in males (adjusted hazard ratio 0.95, 95% confidence interval [CI] 0.91 to 0.99) discharged home, and there was no difference among admitted patients (adjusted hazard ratio 1.00, 95% CI 0.96 to 1.05). Females had high adherence to direct oral anticoagulants (≥80% proportion of days covered) compared to males (discharged: 77.7% versus 74.0%; admitted: 80.0% versus 76.7%; adjusted odds ratio for females: 1.15, 95% CI 1.02 to 1.29). More than half of the females and males had poor warfarin control (time in therapeutic range <65%) regardless of discharge status. In multivariable analyses, there was no sex difference in outcomes except a 1.48-fold (95% CI 1.14 to 1.92) higher risk of stroke in females. CONCLUSION: Females with incident nonvalvular atrial fibrillation discharged from the ED are less likely to receive oral anticoagulants than males. When oral anticoagulant treatment is initiated, females have high adherence to direct oral anticoagulants, and both the sexes have poor warfarin control. At 1 year, females were at a significantly higher risk of developing stroke.

Prevalence of Cardiovascular Disease in a Population-Based Cohort of High-Cost Healthcare Services Users.

BACKGROUND: Data are limited data on the prevalence of cardiovascular disease (CVD) and multimorbidity in contemporary cohorts of high-cost users (HCUs) in Canada.We examined the following: (i) the prevalence of CVD, with a comparison of total healthcare costs among HCUs with vs without CVD; (ii) the contribution of other comorbidities to costs among HCUs with CVD; and (iii) the trajectory of healthcare costs in the years before and after becoming an HCU. METHODS: The study included adult Alberta patients in the Canadian Institutes of Health Research/Canadian Institute for Health Information Dynamic Cohort of Complex, High System Users from 2011-2012 through 2014-2015. We examined total healthcare costs, including hospital, ambulatory care, physician services, and drugs. RESULTS: Among 88,536 HCUs, 23.4% had no CVD, 28.9% were hospitalized with a primary diagnosis of CVD, and 47.7% were hospitalized with a secondary diagnosis of CVD. Total healthcare costs were $2.0 billion (20.4% non-hospital costs), $2.8 billion (24.1% non-hospital costs), and $4.9 billion (19.8% non-hospital costs), respectively, in the 3 groups. Many HCUs with CVD were frail (74.2%) and many had diabetes (33.8%) or chronic obstructive pulmonary disease (27.9%), which contributed to higher costs and mortality. Healthcare expenditures in HCUs with CVD were several times higher than per capita health expenditures in the years prior to, and following, their inclusion in the dynamic HCU cohort. CONCLUSIONS: CVD is very common in HCUs of healthcare. HCUs with CVD have high rates of frailty and multimorbidity. Further research is needed to identify and intervene earlier, in order to flatten the cost curve in these complex patients.

INTRODUCTION: Les données sur la prévalence des maladies cardiovasculaires (MCV) et de la multimorbidité au sein des cohortes contemporaines de grands utilisateurs (GU) du Canada sont limitées. Nous avons examiné ce qui suit : (i) la prévalence des MCV en comparant les coûts totaux des soins de santé entre les GU atteints de MCV et les GU non atteints de MCV; (ii) la contribution des autres comorbidités aux coûts liés aux GU atteints de MCV; (iii) la trajectoire des coûts des soins de santé dans les années avant et après avoir été considérés comme un GU. MÉTHODES: L'étude portait sur des patients adultes de l'Alberta de la Cohorte dynamique de grands utilisateurs du système de santé aux besoins complexes de 2011-2012 à 2014-2015 des Instituts de recherche en santé du Canada et de l'Institut canadien d'information sur la santé. Nous avons examiné les coûts totaux des soins de santé, notamment les coûts hospitaliers, les coûts des soins ambulatoires, des services médicaux et des médicaments. RÉSULTATS: Parmi les 88 536 GU, 23,4 % n'avaient pas de MCV, 28,9 % étaient hospitalisés et avaient un diagnostic principal de MCV, et 47,7 % étaient hospitalisés et avaient un diagnostic secondaire de MCV. Les coûts totaux des soins de santé des 3 groupes étaient respectivement de 2,0 G$ (20,4 % de coûts non hospitaliers), 2,8 G$ (24,1 % de coûts non hospitaliers) et 4,9 G$ (19,8 % de coûts non hospitaliers). Plusieurs GU atteints de MCV étaient fragiles (74,2 %) et beaucoup avaient le diabète (33,8 %) ou une maladie pulmonaire obstructive chronique (27,9 %), qui contribuaient à des coûts et à une mortalité plus élevés. Les dépenses de santé par personne liées aux GU atteints de MCV étaient beaucoup plus élevées que les dépenses de santé par personne dans les années qui précédaient ou suivaient leur inclusion dans la cohorte dynamique de GU atteints de MCV. CONCLUSIONS: Les GU de soins de santé sont très fréquemment atteints de MCV. Les GU atteints de MCV présentent des taux de fragilité et de multimorbidité élevés. D'autres recherches sont nécessaires pour cerner et intervenir plus tôt afin d'aplatir la courbe des coûts chez ces patients aux besoins complexes.

Long-Term Outcomes for Patients With Acute Coronary Syndrome and Nonvalvular Atrial Fibrillation.

Short-term outcomes are worse for patients with acute coronary syndrome (ACS) with a history of nonvalvular atrial fibrillation (NVAF). However, long-term prognosis remains unclear. We linked administrative health databases to identify patients hospitalized with ACS (ST-elevation myocardial infarction [STEMI], non-STEMI [NSTEMI], and unstable angina) between 2008 and 2019 in Alberta, Canada. Patients were stratified according to history of NVAF before hospitalization. The primary outcome was a composite of all-cause mortality, hospitalization for myocardial infarction, or stroke at 3 years. Cox models were constructed to estimate the association between ACS, NVAF, and outcomes. Of 54,309 ACS hospitalizations, 6,351 patients (11.7%) had a history of NVAF. Compared with patients without NVAF, patients with previous NVAF were older (75.6 ± 11.6 vs 64.9 ± 13.4 years), women (35.1% vs 30.0%), had higher comorbid burden (Charlson co-morbidity index 3.0 vs 1.0), and more often presented with NSTEMI (57.5% vs 49.0%). The primary outcome occurred in 37.0% of patients with previous NVAF and 17.4% without (p <0.001). In the multivariable analysis, there was a 1.14-fold (95% confidence interval [CI] 1.09 to 1.20) higher risk of the primary outcome in patients with previous NVAF. There was a significant association with STEMI (adjusted harazard ratio [aHR] 1.24, 95% CI 1.12 to 1.36) and NSTEMI (aHR 1.12, 95% CI 1.06 to 1.19) but not with unstable angina (aHR 1.04, 95% CI 0.90 to 1.22). In conclusion, in this population-based study, we identified that a history of NVAF at ACS presentation is associated with worse long-term prognosis, particularly for STEMI and NSTEMI.

The Introduction of Direct Oral Anticoagulants Has Not Resolved Treatment Gaps for Frail Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: The extent to which the introduction of direct oral anticoagulants (DOACs) influenced treatment patterns in frail and nonfrail patients with nonvalvular atrial fibrillation (NVAF) is unclear. METHODS: This was a retrospective cohort study of all Albertans 20 years or older who were discharged from an emergency department or hospital with a new diagnosis of NVAF between April 1, 2009, and March 31, 2019. The Hospital Frailty Risk Score was used to define frailty and the CHA2DS2-VASc and CHADS-65 scores were used to identify if anticoagulation was indicated. RESULTS: Among 75,796 patients (median age, 75 years; 45% female) with a new diagnosis of NVAF, 17,143 (22.6%) were frail. Although guideline criteria for anticoagulation were more commonly met by frail patients than nonfrail patients (92.1% vs 74.2%, for CHA2DS2-VASc, and 96.8% vs 85.8% for CHADS-65; both P < 0.0001), frail patients were less likely to receive any anticoagulant, even after those with contraindications to anticoagulation were excluded (adjusted odds ratio, 0.61; 95% confidence interval, 0.58-0.64). After DOACs became available, anticoagulant prescribing for patients with guideline indications increased more in nonfrail patients (from 42.4% to 68.2%) than in frail patients (from 29.0% to 52.2%) and frail patients were less likely to receive a DOAC than warfarin (adjusted odds ratio, 0.66; 95% confidence interval, 0.54-0.81). CONCLUSIONS: Although they stand to potentially derive greater benefits from anticoagulation, frail patients were less likely to receive an anticoagulant and, if anticoagulated, they were more likely to receive warfarin than a DOAC. The introduction of DOACs has increased anticoagulation rates but not resolved treatment gaps for frail patients with NVAF.

Concurrent use of P-glycoprotein or Cytochrome 3A4 drugs and non-vitamin K antagonist oral anticoagulants in non-valvular atrial fibrillation.

AIM: To determine the concurrent use of P-glycoprotein (P-gp) or Cytochrome (CYP) 3A4 drugs and non-vitamin K antagonist oral anticoagulants (NOACs) among non-valvular AF (NVAF) patients in clinical practice. METHODS AND RESULTS: Administrative databases identified all adults (≥18 years) with incident or prevalent NVAF who initiated a NOAC in an outpatient or inpatient setting, between July 2012 and March 2019 in Alberta, Canada. Concurrent use was defined as a P-gp or CYP3A4 dispensation in the 100 days prior to and overlapping NOAC dispensation. The P-gp and CYP3A4 drugs were categorized into three groups and drug-drug interactions classified according to the 2018 European Heart Rhythm Association practical guide. Time-varying Cox models calculated the crude hazard ratio (HR) of outcomes at 1-year. A total of 642 255 NOAC dispensations occurred for 36 566 NVAF patients. Of these, 71 643 (11.2%) had a concurrent dispensation of an interacting P-gp or CYP3A4 drug. Overall, the drug-drug interaction was defined as contraindicated in 2.5%, avoid/caution in 2.3%, and for another 6.7% should require a dose adjustment. When all drug-drug interactions were considered, inappropriate NOAC prescribing occurred in 63% (n = 45 080) of dispensations. There was a significantly higher risk of death (HR 1.58, 1.47-1.70) for a drug-drug interaction but not for stroke (P = 0.89) or major bleeding risk (P = 0.13). CONCLUSIONS: The concurrent use of P-gp or CYP3A4 drugs and NOACs was uncommon but important since almost two-thirds of patients with drug-drug interactions had inappropriate NOAC dosing and a higher risk of death. More attention to this issue is needed.