Effect of Qualifying Atherosclerotic Cardiovascular Disease Diagnosis Proximity on Cardiovascular Risk and Benefit of Empagliflozin in the EMPA-REG OUTCOME Trial.

Background: In patients with type 2 diabetes mellitus (T2DM), a history of an ischemic event is associated with increased risk for cardiovascular (CV) disease. Whether patients with T2DM and a recent atherothrombotic diagnosis benefit from early intervention with a sodium-glucose co-transporter 2 inhibitor is unknown. Methods: This study is a secondary analysis of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), which compared empagliflozin to placebo in adults with T2DM and atherosclerotic CV disease (ASCVD). Participants were categorized based on the time since their last qualifying ASCVD diagnosis (≤ 1 year vs > 1 year). Qualifying ASCVD diagnoses included ischemic or hemorrhagic stroke, myocardial infarction, coronary artery disease, and peripheral artery disease. The primary outcome was a composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. Results: A total of 6796 participants (n = 4547 empagliflozin, n = 2249 placebo) were included. Median time since the last qualifying ASCVD diagnosis was 3.8 years (quartile 1-quartile 3: 1.5-7.6), and most qualifying diagnoses occurred > 1 year before randomization (≤ 1 year, n = 1214; > 1 year, n = 5582). Empagliflozin reduced the incidence of the primary outcome irrespective of the time since the last qualifying ASCVD diagnosis (≤ 1 year: hazard ratio 0.82, 95% confidence interval: 0.57-1.16; vs > 1 year: hazard ratio 0.85, 95% confidence interval: 0.72-1.00; P for interaction = 0.84). Results were similar for the composite of CV death or hospitalization for heart failure. Conclusions: Empagliflozin improved CV outcomes in participants with T2DM, irrespective of the time since the last qualifying ASCVD diagnosis at randomization. Prospective trials are necessary to investigate the use of sodium-glucose co-transporter 2 inhibitors at the time of an acute ASCVD event. Trial Registration: EMPA-REG OUTCOME (Clinicaltrials.gov identifier: NCT01131676).

Contexte: Chez les patients atteints de diabète de type 2 (DT2), des antécédents d'accidents ischémiques sont associés à un risque accru de maladie cardiovasculaire (CV). On ignore si une intervention précoce par un inhibiteur du cotransporteur sodium-glucose de type 2 pourrait être bénéfique pour les patients atteints de DT2 ayant récemment reçu un diagnostic d'athérothrombose. Méthodologie: Cette étude est une analyse secondaire de l'essai EMPA-REG OUTCOME ( Empa gliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients­ R emoving E xcess G lucose), qui visait à comparer l'empagliflozine à un placebo chez des adultes atteints de DT2 et d'une maladie CV athéroscléreuse. Les participants ont été répartis selon le temps écoulé depuis leur plus récent diagnostic de maladie CV athéroscléreuse admissible (≤ 1 an vs > 1 an). Les diagnostics de maladies CV athéroscléreuses admissibles comprenaient un accident vasculaire cérébral ischémique ou hémorragique, un infarctus du myocarde, une coronaropathie et une artériopathie périphérique. Le critère d'évaluation principal était composé des décès d'origine CV, des infarctus du myocarde non mortels et des accident vasculaire cérébral non mortels. Résultats: Au total, 6796 participants (n = 4547 pour l'empagliflozine, n = 2249 pour le placebo) ont été inclus. Le temps écoulé médian depuis le diagnostic le plus récent de maladie CV athéroscléreuse admissible était de 3,8 ans (quartile 1-quartile 3 : 1,5-7,6). La plupart des diagnostics admissibles avaient été posés plus de 1 an avant la répartition aléatoire (≤ 1 an, n = 1214; > 1 an, n = 5582). L'empagliflozine a réduit la fréquence des événements constituant le critère d'évaluation principal, sans égard au temps écoulé depuis le plus récent diagnostic de maladie CV athéroscléreuse admissible (≤ 1 an : rapport des risques instantanés 0,82, intervalle de confiance à 95 % : 0,57-1,16; vs > 1 an : rapport des risques instantanés 0,85, intervalle de confiance à 95 % : 0,72-1,00; p pour l'interaction = 0,84). Les résultats étaient comparables à ceux observés pour le critère composé des décès d'origine CV et des hospitalisations pour insuffisance cardiaque. Conclusions: L'empagliflozine a amélioré les issues CV chez les patients atteints de DT2 sans égard au temps écoulé depuis le plus récent diagnostic de maladie CV admissible au moment de la répartition aléatoire. Des essais prospectifs sont nécessaires pour étudier l'utilisation des inhibiteurs du cotransporteur sodium-glucose de type 2 lorsqu'une manifestation de maladie CV athéroscléreuse aiguë survient. Inscription de l'essai: EMPA-REG OUTCOME (numéro d'identification dans clinicaltrials.gov : NCT01131676).

Feasibility and Findings of Including Self-Identified Adult Congenital Heart Disease Patients in the INVESTED Trial.

Background: Adult congenital heart disease (ACHD) patients have significant morbidity and rise in cardiac admissions. Their outcome with high-dose influenza vaccination is unknown in comparison to those without ACHD. Objectives: The purpose of this study was to compare all-cause mortality or cardiopulmonary hospitalizations in self-identified ACHD versus non-ACHD patients receiving high- or low-dose influenza vaccination within the INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure trial. Methods: We prospectively included ACHD patients in the INVESTED (INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure) trial. The primary endpoint was all-cause death or hospitalization for cardiovascular or pulmonary causes. Results: Of the 272 ACHD patients, 132 were randomly assigned to receive high-dose trivalent and 140 to standard-dose quadrivalent influenza vaccine. Compared to the non-ACHD cohort (n = 4,988), ACHD patients were more likely to be younger, women, smokers, have atrial fibrillation, and have a qualifying event of heart failure. The primary outcome was 49.8 events versus 42.8 events per 100 person-years (adjusted HR: 1.17; 95% CI: 0.95-1.45; P = 0.144) in the ACHD group and non-ACHD group, respectively. The interaction between ACHD status and randomized treatment effect was not significant for the primary outcome (P = 0.858). Vaccine-related adverse events were similar in both groups. Conclusions: Patients who self-identify as being ACHD had similar primary outcome of all-cause death or hospitalization for cardiovascular or pulmonary causes compared to non-ACHD cohort. High-dose influenza vaccination was similar to standard-dose influenza vaccination on the primary outcome in patients who self-identify as ACHD.

Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

AIMS: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

Effect of SGLT2 inhibitors on heart failure outcomes and cardiovascular death across the cardiometabolic disease spectrum: a systematic review and meta-analysis.

BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and acute myocardial infarction. Individual trials were powered to study composite outcomes in one disease state. We aimed to evaluate the treatment effect of SGLT2 inhibitors on specific clinical endpoints across multiple demographic and disease subgroups. METHODS: In this systematic review and meta-analysis, we queried online databases (PubMed, Cochrane CENTRAL, and SCOPUS) up to Feb 10, 2024, for primary and secondary analyses of large trials (n>1000) of SGLT2 inhibitors in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease (including acute myocardial infarction). Outcomes studied included composite of first hospitalisation for heart failure or cardiovascular death, first hospitalisation for heart failure, cardiovascular death, total (first and recurrent) hospitalisation for heart failure, and all-cause mortality. Effect sizes were pooled using random-effects models. This study is registered with PROSPERO, CRD42024513836. FINDINGS: We included 15 trials (N=100 952). Compared with placebo, SGLT2 inhibitors reduced the risk of first hospitalisation for heart failure by 29% in patients with heart failure (hazard ratio [HR] 0·71 [95% CI 0·67-0·77]), 28% in patients with type 2 diabetes (0·72 [0·67-0·77]), 32% in patients with chronic kidney disease (0·68 [0·61-0·77]), and 28% in patients with atherosclerotic cardiovascular disease (0·72 [0·66-0·79]). SGLT2 inhibitors reduced cardiovascular death by 14% in patients with heart failure (HR 0·86 [95% CI 0·79-0·93]), 15% in patients with type 2 diabetes (0·85 [0·79-0·91]), 11% in patients with chronic kidney disease (0·89 [0·82-0·96]), and 13% in patients with atherosclerotic cardiovascular disease (0·87 [0·78-0·97]). The benefit of SGLT2 inhibitors on both first hospitalisation for heart failure and cardiovascular death was consistent across the majority of the 51 subgroups studied. Notable exceptions included acute myocardial infarction (22% reduction in first hospitalisation for heart failure; no effect on cardiovascular death) and heart failure with preserved ejection fraction (26% reduction in first hospitalisation for heart failure; no effect on cardiovascular death). INTERPRETATION: SGLT2 inhibitors reduced heart failure events and cardiovascular death in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease. These effects were consistent across a wide range of subgroups within these populations. This supports the eligibility of a large population with cardiorenal-metabolic diseases for treatment with SGLT2 inhibitors. FUNDING: None.

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown. METHODS: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. RESULTS: Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05). CONCLUSIONS: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.

Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). OBJECTIVES: This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. METHODS: In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. RESULTS: Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. CONCLUSIONS: In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674).

Influenza Vaccine Immune Response in Patients With High-Risk Cardiovascular Disease: A Secondary Analysis of the INVESTED Randomized Clinical Trial.

Importance: High-dose trivalent compared with standard-dose quadrivalent influenza vaccine did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations in patients with high-risk cardiovascular disease in the INVESTED trial. Whether humoral immune response to influenza vaccine is associated with clinical outcomes is unknown. Objective: To examine the antibody response to high-dose trivalent compared with standard-dose quadrivalent inactivated influenza vaccine and its associations with clinical outcomes. Design, Setting, and Participants: This secondary analysis is a prespecified analysis of the immune response substudy of the randomized, double-blind, active-controlled INVESTED trial, which was conducted at 157 sites in the United States and Canada over 3 influenza seasons between September 2016 and January 2019. Antibody titers were determined by hemagglutination inhibition assays at randomization and 4 weeks during the 2017-2018 and 2018-2019 seasons. Eligibility criteria included recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor. Data were analyzed from February 2023 to June 2023. Main Outcomes and Measures: Mean antibody titer change, seroprotection (antibody titer level ≥1:40) and seroconversion (≥4-fold increase in titer) at 4 weeks, and the association between seroconversion status and the risk for adverse clinical outcomes. Interventions: High-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine, with revaccination up to 3 seasons. Results: Antibody data were available for 658 of 5260 randomized participants (12.5%; mean [SD] age, 66.2 [11.4] years; 507 male [77.1%], 151 female [22.9%]; 348 with heart failure [52.9%]). High-dose vaccine was associated with an increased magnitude in antibody titers for A/H1N1, A/H3N2, and B-type antigens compared with standard dose. More than 92% of all participants achieved seroprotection for each of the contained antigens, while seroconversion rates were higher in participants who received high-dose vaccine. Seroconversion for any antigen was not associated with the risk for cardiopulmonary hospitalizations or all-cause mortality (hazard ratio, 1.09; 95% CI, 0.79-1.53; P = .59), irrespective of randomized treatment (P = .38 for interaction). Conclusions and Relevance: High-dose vaccine elicited a more robust humoral response in patients with heart failure or prior myocardial infarction enrolled in the INVESTED trial, with no association between seroconversion status and the risk for cardiopulmonary hospitalizations or all-cause mortality. Vaccination to prevent influenza remains critical in high-risk populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02787044.

Evaluating Readability, Understandability, and Actionability of Online Printable Patient Education Materials for Cholesterol Management: A Systematic Review.

BACKGROUND: Dyslipidemia management is a cornerstone in cardiovascular disease prevention and relies heavily on patient adherence to lifestyle modifications and medications. Numerous cholesterol patient education materials are available online, but it remains unclear whether these resources are suitable for the majority of North American adults given the prevalence of low health literacy. This review aimed to (1) identify printable cholesterol patient education materials through an online search, and (2) evaluate the readability, understandability, and actionability of each resource to determine its utility in practice. METHODS AND RESULTS: We searched the MEDLINE database for peer-reviewed educational materials and the websites of Canadian and American national health organizations for gray literature. Readability was measured using the Flesch-Kincaid Grade Level, and scores between fifth- and sixth-grade reading levels were considered adequate. Understandability and actionability were scored using the Patient Education Materials Assessment Tool and categorized as superior (>80%), adequate (50%-70%), or inadequate (<50%). Our search yielded 91 results that were screened for eligibility. Among the 22 educational materials included in the study, 15 were identified through MEDLINE, and 7 were from websites. The readability across all materials averaged an 11th-grade reading level (Flesch-Kincaid Grade Level=11.9±2.59). The mean±SD understandability and actionability scores were 82.8±6.58% and 40.9±28.60%, respectively. CONCLUSIONS: The readability of online cholesterol patient education materials consistently exceeds the health literacy level of the average North American adult. Many resources also inadequately describe action items for individuals to self-manage their cholesterol, representing an implementation gap in cardiovascular disease prevention.

Empagliflozin after Acute Myocardial Infarction.

BACKGROUND: Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown. METHODS: In this event-driven, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, patients who had been hospitalized for acute myocardial infarction and were at risk for heart failure to receive empagliflozin at a dose of 10 mg daily or placebo in addition to standard care within 14 days after admission. The primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis. RESULTS: A total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo. During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile of empagliflozin and were similar in the two trial groups. CONCLUSIONS: Among patients at increased risk for heart failure after acute myocardial infarction, treatment with empagliflozin did not lead to a significantly lower risk of a first hospitalization for heart failure or death from any cause than placebo. (Funded by Boehringer Ingelheim and Eli Lilly; EMPACT-MI ClinicalTrials.gov number, NCT04509674.).

SGLT2 Inhibitors Squeak Out a Win in Patients Post-MI.

James et al1 report the results of the DAPA-MI (DAPAagliflozin in patients without diabetes mellitus with acute Myocardial Infarction) trial, which studied the efficacy and safety of early initiation of dapagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, in patients with acute myocardial infarction (MI) without type 2 diabetes (T2D) or heart failure (HF). The trial was conducted within the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and NICOR (National Institute for Cardiovascular Outcomes Research) registries, leveraging where possible routinely collected health data to augment screening, baseline characteristic ascertainment, and clinical follow-up.

Development and Validation of the CANHEART Population-Based Laboratory Prediction Models for Atherosclerotic Cardiovascular Disease.

BACKGROUND: Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies. OBJECTIVE: To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs). DESIGN: Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models. SETTING: Population-based cohort study in Ontario, Canada. PARTICIPANTS: A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014. MEASUREMENTS: Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years. RESULTS: Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, -0.01 [95% CI, -0.03 to 0.01]) or men (change in c-statistic, -0.01 [CI, -0.04 to 0.02]). LIMITATION: Medication use was not available at the population level. CONCLUSION: The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Association of Neighborhood-Level Marginalization With Health Care Use and Clinical Outcomes Following Hospital Discharge in Patients Who Underwent Coronary Catheterization for Acute Myocardial Infarction in a Single-Payer Health Care System.

BACKGROUND: Canadian data suggest that patients of lower socioeconomic status with acute myocardial infarction receive less beneficial therapy and have worse clinical outcomes, raising questions regarding care disparities even in universal health care systems. We assessed the contemporary association of marginalization with clinical outcomes and health services use. METHODS: Using clinical and administrative databases in Ontario, Canada, we conducted a population-based study of patients aged ≥65 years hospitalized for their first acute myocardial infarction between April 1, 2010 and March 1, 2019. Patients receiving cardiac catheterization and surviving 7 days postdischarge were included. Our primary exposure was neighborhood-level marginalization, a multidimensional socioeconomic status metric. Neighborhoods were categorized by quintile from Q1 (least marginalized) to Q5 (most marginalized). Our primary outcome was all-cause mortality. A proportional hazards regression model with a robust variance estimator was used to quantify the association of marginalization with outcomes, adjusting for risk factors, comorbidities, disease severity, and regional cardiologist supply. RESULTS: Among 53 841 patients (median age, 75 years; 39.1% female) from 20 640 neighborhoods, crude 1- and 3-year mortality rates were 7.7% and 17.2%, respectively. Patients in Q5 had no significant difference in 1-year mortality (hazard ratio [HR], 1.08 [95% CI, 0.95-1.22]), but greater mortality over 3 years (HR, 1.13 [95% CI, 1.03-1.22]) compared with Q1. Over 1 year, we observed differences between Q1 and Q5 in visits to primary care physicians (Q1, 96.7%; Q5, 93.7%) and cardiologists (Q1, 82.6%; Q5, 72.6%), as well as diagnostic testing. There were no differences in secondary prevention medications dispensed or medication adherence at 1 year. CONCLUSIONS: In older patients with acute myocardial infarction who survived to hospital discharge, those residing in the most marginalized neighborhoods had a greater long-term risk of mortality, less specialist care, and fewer diagnostic tests. Yet, there were no differences across socioeconomic status in prescription medication use and adherence.

Association of neighbourhood-level material deprivation with adverse outcomes and processes of care among patients with heart failure in a single-payer healthcare system: A population-based cohort study.

AIM: We studied the association between neighbourhood material deprivation, a metric estimating inability to attain basic material needs, with outcomes and processes of care among incident heart failure patients in a universal healthcare system. METHODS AND RESULTS: In a population-based retrospective study (2007-2019), we examined the association of material deprivation with 1-year all-cause mortality, cause-specific hospitalization, and 90-day processes of care. Using cause-specific hazards regression, we quantified the relative rate of events after multiple covariate adjustment, stratifying by age ≤65 or ≥66 years. Among 395 763 patients (median age 76 [interquartile range 66-84] years, 47% women), there was significant interaction between age and deprivation quintile for mortality/hospitalization outcomes (p ≤ 0.001). Younger residents (age ≤65 years) of the most versus least deprived neighbourhoods had higher hazards of all-cause death (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.10-1.29]) and cardiovascular hospitalization (HR 1.29 [95% CI 1.19-1.39]). Older individuals (≥66 years) in the most deprived neighbourhoods had significantly higher hazard of death (HR 1.11 [95% CI 1.08-1.14]) and cardiovascular hospitalization (HR 1.13 [95% CI 1.09-1.18]) compared to the least deprived. The magnitude of the association between deprivation and outcomes was amplified in the younger compared to the older age group. More deprived individuals in both age groups had a lower hazard of cardiology visits and advanced cardiac imaging (all p < 0.001), while the most deprived of younger ages were less likely to undergo implantable cardioverter-defibrillator/cardiac resynchronization therapy-pacemaker implantation (p = 0.023), compared to the least deprived. CONCLUSION: Patients with newly-diagnosed heart failure residing in the most deprived neighbourhoods had worse outcomes and reduced access to care than those less deprived.

Temporal Association Among Influenza-Like Illness, Cardiovascular Events, and Vaccine Dose in Patients With High-Risk Cardiovascular Disease: Secondary Analysis of a Randomized Clinical Trial.

Importance: Influenza-like illness (ILI) activity has been associated with increased risk of cardiopulmonary (CP) events during the influenza season. High-dose trivalent influenza vaccine was not superior to standard-dose quadrivalent vaccine for reducing these events in patients with high-risk cardiovascular (CV) disease in the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial. Objective: To evaluate whether high-dose trivalent influenza vaccination is associated with benefit over standard-dose quadrivalent vaccination in reducing CP events during periods of high, local influenza activity. Design, Setting, and Participants: This study was a prespecified secondary analysis of INVESTED, a multicenter, double-blind, active comparator randomized clinical trial conducted over 3 consecutive influenza seasons from September 2016 to July 2019. Follow-up was completed in July 2019, and data were analyzed from September 21, 2016, to July 31, 2019. Weekly Centers for Disease Control and Prevention (CDC)-reported, state-level ILI activity was ascertained to assess the weekly odds of the primary outcome. The study population included 3094 patients with high-risk CV disease from participating centers in the US. Intervention: Participants were randomized to high-dose trivalent or standard-dose quadrivalent influenza vaccine and revaccinated for up to 3 seasons. Main Outcomes and Measures: The primary outcome was the time to composite of all-cause death or CP hospitalization within each season. Additional measures included weekly CDC-reported ILI activity data by state. Results: Among 3094 participants (mean [SD] age, 65 [12] years; 2309 male [75%]), we analyzed 129 285 person-weeks of enrollment, including 1396 composite primary outcome events (1278 CP hospitalization, 118 deaths). A 1% ILI increase in the prior week was associated with an increased risk in the primary outcome (odds ratio [OR], 1.14; 95% CI, 1.07-1.21; P < .001), CP hospitalization (OR, 1.13; 95% CI, 1.06-1.21; P < .001), and CV hospitalization (OR, 1.12; 95% CI, 1.04-1.19; P = .001), after adjusting for state, demographic characteristics, enrollment strata, and CV risk factors. Increased ILI activity was not associated with all-cause death (OR, 1.00; 95% CI, 0.88-1.13; P > .99). High-dose compared with standard-dose vaccine did not significantly reduce the primary outcome, even when the analysis was restricted to weeks of high ILI activity (OR, 0.88; 95% CI, 0.65-1.20; P = .43). Traditionally warmer months in the US were associated with lower CV risk independent of local ILI activity. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ILI activity was temporally associated with increased CP events in patients with high-risk CV disease, and a higher influenza vaccine dose did not significantly reduce temporal CV risk. Other seasonal factors may play a role in the coincident high rates of ILI and CV events. Trial Registration: ClinicalTrials.gov Identifier: NCT02787044.

Baseline characteristics of patients enrolled in the EMPACT-MI trial.

AIMS: Empagliflozin has been shown to reduce the risk of adverse cardiovascular outcomes in patients with type 2 diabetes and in those with heart failure. The impact of empagliflozin in post-acute myocardial infarction (AMI) patients is unknown. METHODS AND RESULTS: The Study to Test the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction (EMPACT-MI) trial screened 6610 participants with AMI and randomized 6522 to empagliflozin or placebo in addition to standard of care. The median (interquartile) age was 64 (56-71) years and 75.1% of patients were male. Major comorbidities included hypertension (69.1%), type 2 diabetes (31.7%), prior myocardial infarction (13.0%), and atrial fibrillation (10.9%). The majority (74.3%) of patients presented with an ST-elevation myocardial infarction. Overall, 56.9% of patients had acute signs or symptoms of congestion requiring treatment and 78.3% had left ventricular systolic dysfunction with ejection fraction <45%. Clinical characteristics, including baseline demographics, rates of revascularization, and cardiovascular medications at discharge were largely comparable to recent trials of the post-AMI population. CONCLUSION: The EMPACT-MI trial will establish the benefit and risks of empagliflozin treatment in patients with AMI.

Morbidity and Mortality Associated With Heart Failure in Acute Coronary Syndrome: A Pooled Analysis of 4 Clinical Trials.

BACKGROUND: Heart failure (HF) may complicate acute coronary syndrome (ACS) and is associated with a high burden of short- and long-term morbidity and mortality. Only limited data regarding future ischemic events and rehospitalization are available for patients who suffer HF before or during ACS. METHODS: A secondary analysis of 4 large ACS trials (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) using Cox proportional hazards models was performed to investigate the association of HF status (no HF, chronic HF, de novo HF) at presentation for ACS with all-cause and cardiovascular death, major adverse cardiovascular event (MACE ), myocardial infarction, stroke, and hospitalization for heart failure (HHF) by 1 year. Cumulative incidence plots are presented at 30 days and 1 year. RESULTS: A total of 11.1% of the 47,474 patients presenting with ACS presented with evidence of acute HF, 55.0% of whom presented with de novo HF. Patients with chronic HF presented with evidence of acute HF at a higher rate than those with no previous HF (40.3% vs 6.9%). Compared to those without HF, those with chronic and de novo HF had higher rates of all-cause mortality (adjusted hazard ratio [aHR] 2.01, 95% confidence interval [CI] 1.72-2.34 and aHR 1.47, 95% CI1.15-1.88, respectively), MACE (aHR 1.47, 95% CI1.31-1-.66 and aHR 1.38, 95% CI1.12-1.69), and HHF (aHR 2.29, 95% CI2.02-2.61 and aHR 1.48, 95% CI 1.20-1.82) at 1 year. CONCLUSION: In this large cohort of patients with ACS, both prior and de novo HF complicating ACS were associated with significantly higher risk-adjusted rates of death, ischemic events and HHF at 30 days and 1 year. Further studies examining the association between HF and outcomes in this high-risk population are warranted, especially given the advent of more contemporary HF therapies.