Association of Medication Intensity and Stages of Airflow Limitation With the Risk of Hospitalization or Death in Patients With Heart Failure and Chronic Obstructive Pulmonary Disease
Authors: Claire A. Lawson, Mamas A. Mamas, Peter W. Jones, Lucy Teece, Gerry McCann, Kamlesh Khunti, Umesh T. Kadam
Journal: JAMA Network Open (2018)

<h3>Importance</h3> In heart failure (HF), chronic obstructive pulmonary disease (COPD) increases the risk of poor outcomes, but the effect of COPD severity is unknown. This information is important for early intervention tailored to the highest-risk groups. <h3>Objectives</h3> To determine the associations between COPD medication intensity or stage of airflow limitation and the risk of hospitalization or death in patients with HF. <h3>Design, Setting, and Participants</h3> This UK population-based, nested case-control study with risk-set sampling used the Clinical Practice Research Datalink linked to Hospital Episode Statistics between January 1, 2002, to January 1, 2014. Participants included patients aged 40 years and older with a new diagnosis of HF in their family practice clinical record. Data analysis was conducted from 2017 to 2018. <h3>Exposures</h3> In patients with HF, those with COPD were compared with those without it. International COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD]) guidelines were used to stratify patients with COPD by 7 medication intensity levels and 4 airflow limitation severity stages using automatically recorded prescriptions and routinely requested forced expiratory volume in 1 second (FEV<sub>1</sub>) data. <h3>Main Outcomes and Measures</h3> First all-cause admission or all-cause death. <h3>Results</h3> There were 50 114 patients with new HF (median age, 79 years [interquartile range, 71-85 years]; 46% women) during the study period. In patients with HF, COPD (18 478 [13.8%]) was significantly associated with increased mortality (adjusted odds ratio [AOR], 1.31; 95% CI, 1.26-1.36) and hospitalization (AOR, 1.33; 95% CI, 1.26-1.39). The 3 most severe medication intensity levels showed significantly increasing mortality associations from full inhaler therapy (AOR, 1.17; 95% CI, 1.06-1.29) to oral corticosteroids (AOR, 1.69; 95% CI, 1.57-1.81) to oxygen therapy (AOR, 2.82; 95% CI, 2.42-3.28). The respective estimates for hospitalization were AORs of 1.17 (95% CI, 1.03-1.33), 1.75 (95% CI, 1.59-1.92), and 2.84 (95% CI, 1.22-3.63). Availability of spirometry data was limited but showed that increasing airflow limitation was associated with increased risk of mortality, with the following AORs: FEV<sub>1 </sub>80% or more, 1.63 (95% CI, 1.42-1.87); FEV<sub>1</sub>50% to 79%, 1.69 (95% CI, 1.56-1.83); FEV<sub>1</sub>30% to 49%, 2.21 (95% CI, 2.01-2.42); FEV<sub>1</sub>less than 30%, 2.93 (95% CI, 2.49-3.43). The strength of associations between FEV<sub>1</sub>and hospitalization risk were similar among stages ranging from FEV<sub>1</sub>80% or more (AOR, 1.48; 95% CI, 1.31-1.68) to FEV<sub>1</sub>less than 30% (AOR, 1.73; 95% CI, 1.40-2.12). <h3>Conclusions and Relevance</h3> In the UK HF community setting, increasing COPD severity was associated with increasing risk of mortality and hospitalization. Prescribed COPD medication intensity and airflow limitation provide the basis for targeting high-risk groups.