Background/Objectives: Fixed-dose triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) at high risk of exacerbations; however, direct comparative effectiveness data between available triple therapy regimens remain limited. We compared real-world clinical outcomes among adults with COPD receiving fluticasone furoate/vilanterol/umeclidinium (FF/VI/UMEC) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR). Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Research Network. Adults with a spirometrically confirmed diagnosis of COPD who received fluticasone furoate/vilanterol/umeclidinium (FF/VI/UMEC) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR) between July 2020 and August 2024 were included in the analysis. A 365-day landmark period was applied to establish maintenance therapy, with outcome follow-up beginning 1 year after treatment initiation. Patients were followed for outcomes through August 2025, the date of database analysis. After 1:1 propensity score matching, treatment groups were compared for COPD exacerbations, acute respiratory failure (ARF), hospitalization, and all-cause mortality using RR and Cox proportional hazards analyses. Results: In matched cohorts, FF/VI/UMEC was associated with a significantly higher risk of COPD exacerbations (5.6% vs. 3.9%; RR 1.44; 95% CI 1.30–1.59; p < 0.001) and ARF (2.5% vs. 1.9%; RR 1.28; 95% CI 1.11–1.46; p < 0.001) compared with BUD/GLY/FOR. Time-to-event analyses demonstrated lower event-free probability for exacerbations (HR 1.35; (95% CI 1.21–1.50) and ARF (HR 1.15; (95% CI 1.00–1.32))). All-cause mortality was numerically higher in the FF/VI/UMEC cohort (5.2% vs. 4.7%; RR 1.09; 95% CI 1.00–1.19; p = 0.050); however, time-to-event analysis did not demonstrate a statistically significant difference. Hospitalization rates were similar between groups. Conclusions: In this large propensity score-matched real-world cohort study, patients receiving BUD/GLY/FOR experienced lower rates of COPD exacerbations and acute respiratory failure than those receiving FF/VI/UMEC. Because of the retrospective observational nature of the analysis, these findings should be considered hypothesis-generating and require confirmation in prospective comparative effectiveness studies.
Finding the Best Fit: A Head-To-Head Comparison of Triple Therapy Regimens in COPD
Abstract Introduction: Chronic obstructive pulmonary disease (COPD) represents a significant global health challenge, particularly in its moderate to severe cases, where effective management is crucial to improving patient outcomes. The integration of inhaled corticosteroids with long-acting β2-adrenoceptor agonists and long-acting muscarinic antagonists in fixed-dose combinations has emerged as a cornerstone of therapy. This study evaluates the efficacy of two triple therapy regimens — Glycopyrrolate, Budesonide, and Formoterol Fumarate (GLY/BUD/FOR) and Fluticasone Furoate, Vilanterol, and Umeclidinium (FF/VI/UMEC) —in adults aged 45 and older with diagnosed COPD with FEV1/FVC < 70% to assess the impact of these regimens on the preventing COPD exacerbations and acute hypoxemic respiratory failure. Methods: A retrospective cohort analysis was conducted using the TriNetX database. Patients with moderate to severe COPD and FEV1/FVC < 70% were identified based on ICD codes, and two cohorts were formed based on the prescribed inhaler therapy: GLY/BUD/FOR and FF/VI/UMEC. Patients with comorbid asthma, heart failure, or pneumonia were excluded. A 1:1 propensity-score matching (PSM) analysis was performed to balance covariates such as age, gender, smoking status, and baseline lung function to minimize confounding and bias. Post-matching, both had 16,052 patients. Ultimately, 23,331 patients (FF/VI/UMEC: 11,234, GLY/BUD/FOR: 12,097) with a mean age of 67.4 ± 10.1 years and 55.3% males were included. Results: Among groups, 10.4% of patients on FF/VI/UMEC experienced COPD exacerbations compared to 6.7% on GLY/BUD/FOR (Risk Ratio: 1.55, 95% CI: 1.42-1.69, p < 0.001). Kaplan-Meier analysis showed a lower survival probability in the FF/VI/UMEC group (77.7% vs. 83.9%, p < 0.001). For acute respiratory failure, 3.5% of patients on FF/VI/UMEC experienced this outcome compared to 2.8% on GLY/BUD/FOR (Risk Ratio: 1.28, 95% CI: 1.12-1.45, p = 0.003). Conclusion: Our study suggests that FF/VI/UMEC demonstrated an increased risk of COPD exacerbations and acute hypoxic respiratory failure compared to the group receiving GLY/BUD/FOR. This indicates that GLY/BUD/FOR may provide enhanced protective benefits in patients with moderate to severe COPD, improving disease management and minimizing healthcare resource utilization. Further studies are warranted to explore the long-term benefits and potential mechanisms underlying the observed differences.
Non-calcified Coronary Plaque Burden is Related to Epicardial Adipose Tissue and Peri-coronary Adipose Tissue Attenuation in Heart Failure With Preserved Ejection Fraction
OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.