Inhaled corticosteroids and risk of cardiovascular events in chronic obstructive pulmonary disease: a nationwide cohort study in Denmark.
Cardiovascular disease is a major comorbidity in chronic obstructive pulmonary disease (COPD). Previous studies evaluating the association between inhaled corticosteroids (ICS) and cardiovascular events (CVEs) in COPD have yielded conflicting results and a potential dose-response relationship remains unclear.
To determine the association between ICS exposure and risk of CVE in COPD patients.
In this nationwide, retrospective register-based cohort study, we included patients with a specialist-verified COPD diagnosis between January 2008 and January 2022. ICS exposure was quantified as mean daily budesonide-equivalent dose redeemed in the year prior to index and categorised as none, low (>0 µg/day and <400 µg/day), moderate (400-800 µg/day) or high (>800 µg/day). We assessed CVE risk using adjusted cause-specific Cox proportional hazards models, with additional sensitivity analyses including a complete-case analysis, time-varying Cox regression, Fine-Gray competing risk model, and a negative control outcome analysis.
Among 82 327 patients, 8948 (10.9 %) experienced a CVE during a 1-year follow-up. In the primary analysis, low- and moderate-dose ICS was associated with a significantly reduced CVE rate compared with no ICS use. A modest decrease in CVE rate was observed for moderate-dose ICS largely across all sensitivity analyses.
ICS use in COPD was not associated with an increased risk of CVE at any dose level. A modest association with reduction in CVE risk was confined to moderate-dose ICS. These findings support the cardiovascular safety of ICS and reinforce that ICS prescribing should be guided by exacerbation risk and symptom burden rather than cardiovascular concern.
To determine the association between ICS exposure and risk of CVE in COPD patients.
In this nationwide, retrospective register-based cohort study, we included patients with a specialist-verified COPD diagnosis between January 2008 and January 2022. ICS exposure was quantified as mean daily budesonide-equivalent dose redeemed in the year prior to index and categorised as none, low (>0 µg/day and <400 µg/day), moderate (400-800 µg/day) or high (>800 µg/day). We assessed CVE risk using adjusted cause-specific Cox proportional hazards models, with additional sensitivity analyses including a complete-case analysis, time-varying Cox regression, Fine-Gray competing risk model, and a negative control outcome analysis.
Among 82 327 patients, 8948 (10.9 %) experienced a CVE during a 1-year follow-up. In the primary analysis, low- and moderate-dose ICS was associated with a significantly reduced CVE rate compared with no ICS use. A modest decrease in CVE rate was observed for moderate-dose ICS largely across all sensitivity analyses.
ICS use in COPD was not associated with an increased risk of CVE at any dose level. A modest association with reduction in CVE risk was confined to moderate-dose ICS. These findings support the cardiovascular safety of ICS and reinforce that ICS prescribing should be guided by exacerbation risk and symptom burden rather than cardiovascular concern.
Authors
Nielsen Nielsen, Borremose Wedervang Borremose Wedervang, Vognsen Vognsen, Frost Frost, Jordan Jordan, Vikjord Vikjord, Mathioudakis Mathioudakis, Jensen Jensen, Sivapalan Sivapalan
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