Statin use and exacerbations in individuals with chronic obstructive pulmonary disease

Background We tested the hypothesis that statin use in individuals with COPD is associated with a reduced risk of exacerbations. Methods We identified 5794 individuals with COPD and a measurement of C reactive protein (CRP) in the Copenhagen General Population Study (2003-2008). During 3 years of follow-up we recorded exacerbations with hospital admissions or oral corticosteroid treatment. In a nested case-control design, matching on age, gender, smoking, COPD severity and comorbidity, we estimated the association between statin use and exacerbations. In addition, we examined the association between statin use and high CRP (>3 mg/L), and the association between high CRP and exacerbations during follow-up. Results Statin use was associated with reduced odds of exacerbations in crude analysis, OR=0.68 (95% CI 0.51 to 0.91, p=0.01), as well as in multivariable conditional logistic regression analysis, OR=0.67 (0.48 to 0.92, p=0.01). However, in the subgroup with the most severe COPD and without cardiovascular comorbidity, we observed a null association between statin use and exacerbations, OR=1.1 (0.5 to 2.1, p=0.83). Furthermore, statin use was associated with reduced odds of a high CRP, OR=0.69 (0.56 to 0.85, p<0.001), and a high CRP was associated with an increased risk of exacerbations, HR=1.62 (1.35 to 1.94, p<0.001). We estimated the percentage of excess risk of the association of statin use with exacerbations possibly mediated through a reduction of CRP to be 14% (4-51%). Conclusions Statin use was associated with reduced odds of exacerbations in individuals with COPD from the general population, although this was not apparent in those with the most severe COPD without cardiovascular comorbidity. Statins may thus only associate with reduced risk of exacerbations in patients with COPD with coexisting cardiovascular disease.