Relationship between heart failure and the risk of acute exacerbation of COPD

Abstract

Rationale: Heart failure (HF) management in chronic obstructive pulmonary disease (COPD) is often delayed or suboptimal.

Objectives: To examine the effect of HF and HF medication use on moderate-to-severe COPD exacerbations.

Methods and measurements: Retrospective cohort studies from 2006 to 2016 using nationally representative English primary care electronic healthcare records linked to national hospital and mortality data. Patients with COPD with diagnosed and possible HF were identified. Possible HF was defined as continuous loop diuretic use in the absence of a non-cardiac indication. Incident exposure to HF medications was defined as ≥2 prescriptions within 90 days with no gaps >90 days during ≤6 months of continuous use; prevalent exposure as 6+ months of continuous use. HF medications investigated were angiotensin receptor blockers, ACE inhibitors, beta-blockers, loop diuretics and mineralocorticoid receptor antagonists. Cox regression, stratified by sex and age, further adjusted for patient characteristics, was used to determine the association of HF with exacerbation risk.

Main results: 86 795 patients with COPD were categorised as no evidence of HF (n=60 047), possible HF (n=8476) and newly diagnosed HF (n=2066). Newly diagnosed HF (adjusted HR (aHR): 1.45, 95% CI: 1.30 to 1.62) and possible HF (aHR: 1.65, 95% CI: 1.58 to 1.72) similarly increased exacerbation risk. Incident and prevalent use of all HF medications were associated with increased exacerbation risk. Prevalent use was associated with reduced exacerbation risk compared with incident use.

Conclusions: Earlier opportunities to improve the diagnosis and management of HF in the COPD population are missed. Managing HF may reduce exacerbation risk in the long term.

Keywords: COPD epidemiology; COPD exacerbations; clinical epidemiology.

Figure 1

Derivation of the study populations. For analyses of the influences of HF and HF medications on exacerbation risk from the CPRD. CKD, chronic kidney disease; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; CPRD, Clinical Practice Research Datalink; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HES, Hospital Episode Statistics; IMD, Index of Multiple Deprivation; ONS, Office for National Statistics.

Figure 2

Effect of newly diagnosed and possible HF on AECOPD risk. aHR comparing risk of moderate-to-severe AECOPD in patients with COPD with possible HF and newly diagnosed HF compared with patients with COPD without evidence of HF. Estimates from stratified Cox regression stratified by matched set (sex and age) and adjusted for smoking status, body mass index, index of multiple deprivation, exacerbation history, severity of airflow limitation, inhaler use, a history of cardiovascular disease and cardiovascular medication use. AECOPD, acute exacerbations of chronic obstructive pulmonary disease; aHR, adjusted HR; COPD, chronic obstructive pulmonary disease; HF, heart failure.

Figure 3

Effect of HF medication use on AECOPD risk. aHR for the risk of moderate-to-severe AECOPD in patients with diagnosed HF comparing incident medication use (<6 months) with non-use, (B) prevalent medication use (≥6 months) with non-use and (C) prevalent medication use with incident medication use for (I) ACEi, (II) ARB, (III) BB, (IV) LD and (v) MRA. Estimates with 95% CIs from Cox regression adjusted for age, sex, smoking status, body mass index, Index of Multiple Deprivation, exacerbation history, severity of airflow limitation, inhaler use, a history of cardiovascular disease and cardiovascular medication use. ACEi, ACE inhibitor; AECOPD, acute exacerbations of chronic obstructive pulmonary disease; aHR, adjusted HR; ARB, angiotensin receptor blockers; BB, beta-blockers; COPD, chronic obstructive pulmonary disease; HF, heart failure; LD, loop diuretics; MRA, mineralocorticoid receptor antagonists.