A2257 - Metoprolol Attenuates Exacerbation Risk in Subjects with Elevated Coronary Artery Calcium Scores: A Post-Hoc Analysis of BLOCK-COPD
Author Block: R. C. Wade¹, S. Ling², E. Helgeson², H. Voelker², W. W. Labaki³, D. Meza⁴, O. A. O'Corragain⁵, J. Y. So⁶, G. J. Criner⁵, M. K. Han³, R. Kalhan⁴, R. M. Reed⁶, M. T. Dransfield⁷, J. M. Wells⁷; ¹Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States, ²Department of Biostatistics, University of Minnesota, Minneapolis, MN, United States, ³Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States, ⁴Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, IL, United States, ⁵Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, PA, United States, ⁶Division of Pulmonary and Critical Care Medicine, University of Maryland, Baltimore, MD, United States, ⁷Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham & Birmingham VA Medical Center, Birmingham, AL, United States.
Rationale: In 2018, BLOCK-COPD (Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) evaluated the effect of metoprolol on exacerbation risk and mortality in a COPD population without indications for beta-blocker use. BLOCK-COPD failed to demonstrate a benefit and suggested potential harm resulting in termination of the study. We hypothesized that imaging metrics, the pulmonary artery to aorta (PA:A) ratio and visual coronary artery calcium (CAC) score, would predict exacerbation risk and identify a differential response to metoprolol treatment in this cohort. Methods: Subjects enrolled in BLOCK-COPD at a single center were included if they had a thoracic computed tomography (CT) scan to obtain the necessary measurements; CT scans within 30 days of an exacerbation were excluded. A reviewer blinded to treatment status and clinical parameters measured the diameter of the PA and aorta at the level of the PA bifurcation to determine a PA:A ratio; a ratio >1 indicated PA enlargement (PAE). The reviewer scored the coronary arteries for intraluminal calcium using the visual (Weston) score. A value of 0-3 was assigned to each vessel (left main [LM], left anterior descending, left circumflex, and right coronary artery). Cox proportional hazard models assessed for interaction between PAE or CAC scores and treatment assignment on time to first exacerbation of any severity. Analyses were adjusted for age, sex, baseline FEV₁ percent predicted, hospitalizations in the prior year, steroid/antibiotic courses in the prior year, and CAT (COPD assessment test) score. Results: Fifty-three subjects were included in the analysis; 24 randomized to metoprolol and 29 to placebo. There were 24 mild exacerbations, 11 severe-very severe exacerbations, and 2 deaths. PAE was associated with a decreased time to first severe-very severe exacerbation (HR: 6.79, 95% CI: 1.61-28.72, p<0.01). In the placebo group, there was no association between LM CAC and time-to-exacerbation (HR: 1.35, 95% CI: 0.70-2.59, p-value=0.37), but subjects in the metoprolol group with higher LM CAC scores had reduced exacerbation risk (HR: 0.50, 95% CI: 0.26-0.96, p=0.04) corresponding to differential association between treatment assignment and LM CAC score on time-to-exacerbation (ratio of hazard ratios: 0.37, 95% CI: 0.15-0.94, p=0.04). Conclusions: Pulmonary artery enlargement is associated with increased risk of severe-very severe exacerbations which confirms findings from prior studies. Individuals assigned to metoprolol with higher CAC scores had decreased exacerbation risk suggesting this cardiac imaging metric could inform therapy in future clinical trials. Further investigation of these findings is warranted.