COPD exacerbations and Major Adverse Cardiovascular Events (MACE) after first MACE

Abstract

Whether major adverse cardiovascular events (MACE) are associated with subsequent COPD exacerbations is unknown. In a generalisable COPD cohort, we determined whether (1) MACE was associated with subsequent exacerbations (by MACE-subtype, exacerbation severity, and timeframe), and (2) exacerbation-plus-MACE was associated with second non-fatal MACE. We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) Aurum primary care database, linked with inpatient secondary care (Hospital Episode Statistics) and mortality (Office of National Statistics), between 01/01/2010 and 27/03/2021. For aim (1), exposure was MACE (first hospitalised acute coronary syndrome, arrhythmia, ischaemic stroke, or heart failure) versus no MACE, and outcome was exacerbations. For aim (2), exposure was exacerbation within the year preceding first MACE (MACE-plus-exacerbation), versus MACE alone, and outcome second non-fatal MACE. As an exploratory analysis, we determined whether inhaled corticosteroids (ICS) were associated with subsequent MACE in people with different cardiovascular histories. We implemented Cox proportional hazard regressions. Amongst 291 161 individuals with COPD (21 108[7.2%] with MACE), MACE and MACE-subtypes were associated with subsequent exacerbations (aHR[95%CI]=1.32[1.29–1.35], p<0.00001), driven primarily by severe exacerbations (moderate: aHR[95%CI]=1.06[1.02–1.10], p=0.0009; severe: aHR[95%CI]=1.86[1.78–1.94], p<0.00001). Exacerbation risk was reduced in days 1–14 post-MACE (aHR[95%CI]=0.78[0.68–0.89], p<0.00001), likely due to healthcare contact, followed by a sharp increase between days 15–30 (aHR[95%CI]=2.12[1.92–2.34], p<0.00001), and a reduction to average risk over one year. Exacerbation-plus-MACE was not associated with second non-fatal MACE (aHR[95%CI]=1.07[0.99–1.14]), regardless of MACE-subtype and exacerbation severity. ICS, compared with long-acting bronchodilators, was not associated with subsequent MACE, regardless of cardiovascular history. MACE was associated with subsequent exacerbations, particularly severe exacerbations. Risk is highest 15–30 days post-MACE. Exacerbation-plus-MACE was not associated with second non-fatal MACE compared with MACE alone.