Statins and Mortality in COPD: A Methodological Review of Observational Studies

Randomized controlled trials and observational studies have reported conflicting results on the potential beneficial effects of statins on mortality in patients with chronic obstructive pulmonary disease (COPD). We performed a systematic search of the literature to review all observational studies r...

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Bibliographic Details
Published in:Chronic obstructive pulmonary disease 2023-12, Vol.20 (1), p.284-291
Main Authors: Sule, Naheemot Olaoluwa, Suissa, Samy
Format: Article
Language:English
Subjects:
confounding
database studies
immortal time bias
selection bias
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Summary:Randomized controlled trials and observational studies have reported conflicting results on the potential beneficial effects of statins on mortality in patients with chronic obstructive pulmonary disease (COPD). We performed a systematic search of the literature to review all observational studies reporting relative risks of death with statin use in COPD, focusing on potential sources of bias. We identified 15 observational studies, out of 2835, of which 12 were affected by time-related and other biases and the remaining 3 by confounding bias. All 15 studies were also subject to confounding bias due to lack of adjustment for important COPD-related factors. The risk of death associated with statin use was reduced across all 15 studies (pooled relative risk (PRR) 0.66; 95% CI: 0.59-0.74). The reduction was observed in 7 studies with immortal time bias (PRR 0.62; 95%: 0.53-0.72), two with collider-stratification bias (PRR 0.60; 95% CI: 0.45-0.80), one with time-window bias (RR 0.61; 95% CI: 0.38-0.98), one with immeasurable time bias (RR 0.50; 95% CI: 0.40-0.62), and one with exposure misclassification (RR 0.86; 95% CI: 0.72-1.03). The three studies that avoided these biases were, however, affected by confounding bias resulting in a PRR of 0.77 (95% CI: 0.61-0.98). In conclusion, the observational studies investigating statin use and mortality in COPD are affected by major biases, many of which can result in spurious protective effects. Well-designed observational studies that carefully emulate randomized trials are needed to resolve this uncertainty regarding the potential beneficial benefits of statins on mortality in patients with COPD.
ISSN:1541-2555
1541-2563
DOI:10.1080/15412555.2023.2242489