Statins for the prevention of exacerbations in COPD: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: The role of statins in reduction of acute exacerbations in chronic obstructive pulmonary disease (COPD) remains unclear. This systematic review and meta-analysis aimed to determine the preventive effect of statins on exacerbations in COPD patients. METHODS: A systematic search was conducted in PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COPD with statins, compared with placebo, were reviewed. Estimated effects of included studies were pooled as risk ratios (RRs) and weighted mean differences (WMDs), with 95% confidence intervals (CIs). The certainty of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. RESULTS: Three RCTs (enrolling 1190 patients) met the inclusion criteria. Compared with placebo, the exacerbation related hospitalization rate (RR 0.87, 95% CI 0.77 to 0.97; GRADE = low) and severe exacerbation rate (RR 0.88, 95% CI 0.78 to 0.99; low) were significantly lower in statins groups. There was no statistically significant difference in moderate exacerbation rate (RR 0.71, 95% CI 0.48 to 1.04; very low), annualized exacerbation rate (WMD -0.21 per person-year, 95% CI -0.61 to 0.20; very low), and annualized moderate-to-severe exacerbation rate (WMD -0.21 per person-year, 95% CI -0.57 to 0.15; very low) between the two groups. CONCLUSIONS: In the absence of single-inhaler triple therapy (SITT), statins were associated with a reduction in severe exacerbations and hospitalization rates of COPD. Given the limitations of the evidence we found, further large-scale, high-quality studies are needed to clarify the impact of statins on prognosis and the beneficiary population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42025644971.