RESUMEN

BACKGROUND: An immediate, temporal risk of heart failure and arrhythmias after a Chronic Obstructive Pulmonary Disease (COPD) exacerbation has been demonstrated, particularly in the first month post-exacerbation. However, the clinical profile of patients who develop heart failure (HF) or atrial fibrillation/flutter (AF) following exacerbation is unclear. Therefore we examined factors associated with people being hospitalized for HF or AF, respectively, following a COPD exacerbation. METHODS: We conducted two nested case-control studies, using primary care electronic healthcare records from the Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, Office for National Statistics for mortality, and socioeconomic data (2014-2020). Cases had hospitalization for HF or AF within 30 days of a COPD exacerbation, with controls matched by GP practice (HF 2:1;AF 3:1). We used conditional logistic regression to explore demographic and clinical factors associated with HF and AF hospitalization. RESULTS: Odds of HF hospitalization (1,569 cases, 3,138 controls) increased with age, type II diabetes, obesity, HF and arrhythmia history, exacerbation severity (hospitalization), most cardiovascular medications, GOLD airflow obstruction, MRC dyspnea score, and chronic kidney disease. Strongest associations were for severe exacerbations (adjusted odds ratio (aOR)=6.25, 95%CI 5.10-7.66), prior HF (aOR=2.57, 95%CI 1.73-3.83), age≥80 years (aOR=2.41, 95%CI 1.88-3.09), and prior diuretics prescription (aOR=2.81, 95%CI 2.29-3.45). Odds of AF hospitalization (841 cases, 2,523 controls) increased with age, male sex, severe exacerbation, arrhythmia and pulmonary hypertension history and most cardiovascular medications. Strongest associations were for severe exacerbations (aOR=5.78, 95%CI 4.45-7.50), age≥80 years (aOR=3.15, 95%CI 2.26-4.40), arrhythmia (aOR=3.55, 95%CI 2.53-4.98), pulmonary hypertension (aOR=3.05, 95%CI 1.21-7.68), and prescription of anticoagulants (aOR=3.81, 95%CI 2.57-5.64), positive inotropes (aOR=2.29, 95%CI 1.41-3.74) and anti-arrhythmic drugs (aOR=2.14, 95%CI 1.10-4.15). CONCLUSIONS: Cardiopulmonary factors were associated with hospitalization for HF in the 30 days following a COPD exacerbation, while only cardiovascular-related factors and exacerbation severity were associated with AF hospitalization. Understanding factors will help target people for prevention.

Asunto(s)

Fibrilación Atrial , Aleteo Atrial , Insuficiencia Cardíaca , Hospitalización , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Femenino , Estudios de Casos y Controles , Anciano , Fibrilación Atrial/epidemiología , Insuficiencia Cardíaca/epidemiología , Aleteo Atrial/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Hospitalización/estadística & datos numéricos , Progresión de la Enfermedad , Modelos Logísticos

RESUMEN

Rationale: Cardiovascular events after chronic obstructive pulmonary disease (COPD) exacerbations are recognized. Studies to date have been post hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally.Objectives: We explore temporal relationships between moderate and severe exacerbations and incident, nonfatal hospitalized cardiovascular events in a primary care-derived COPD cohort.Methods: We included people with COPD in England from 2014 to 2020, from the Clinical Practice Research Datalink Aurum primary care database. The index date was the date of first COPD exacerbation or, for those without exacerbations, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischemic stroke, and pulmonary hypertension) from linked hospital data. Adjusted Cox regression models were used to estimate average and time-stratified adjusted hazard ratios (aHRs).Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation; 119,124 (55.8%) had moderate exacerbations, and 27,324 (12.8%) had severe exacerbations. A total of 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate after any exacerbation (1-14 d; aHR, 3.19 [95% confidence interval (CI), 2.71-3.76]), followed by progressively declining yet maintained effects, elevated after one year (aHR, 1.84 [95% CI, 1.78-1.91]). Hazard ratios were highest 1-14 days after severe exacerbations (aHR, 14.5 [95% CI, 12.2-17.3]) but highest 14-30 days after moderate exacerbations (aHR, 1.94 [95% CI, 1.63-2.31]). Cardiovascular outcomes with the greatest two-week effects after a severe exacerbation were arrhythmia (aHR, 12.7 [95% CI, 10.3-15.7]) and heart failure (aHR, 8.31 [95% CI, 6.79-10.2]).Conclusions: Cardiovascular events after moderate COPD exacerbations occur slightly later than after severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately after an exacerbation presents a critical opportunity for clinical intervention and treatment optimization to prevent future cardiovascular events.

Asunto(s)

Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Progresión de la Enfermedad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Arritmias Cardíacas , Insuficiencia Cardíaca/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología

RESUMEN

Objective: To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases. Materials and Methods: We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335 931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables. Results: In Search A, we identified 165 150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317 963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19 696 prescriptions; C:1145) and SAMA inhalers (A and B:35 310; C:564). Discussion: We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses. Conclusions: Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.