Baseline inflammatory status affects the prognostic impact of statins in patients with peripheral arterial disease

ABSTRACT Background Statins bring favorable effects on the clinical prognosis of patients with atherosclerotic disease partly through their anti-inflammatory properties. However, this effect has not been fully verified in patients with peripheral arterial disease (PAD). We aimed to test whether statins exert different prognostic effects depending on the degrees of inflammation in patients with PAD. Methods This study was a sub-analysis of a multicenter prospective cohort of 2,321 consecutive patients with PAD who received endovascular therapy (EVT). After excluding patients without information on C-reactive protein (CRP) levels at the time of index EVT, 1,974 patients (1,021 statin users and 953 non-users) were ultimately analyzed. Enrolled patients were classified into four groups depending on CRP levels: low CRP (1.0 mg/dL). A composite of death, stroke, myocardial infarction, and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category. Results Overall, statin users showed a significantly lower event rate than non-users (log-rank, p<0.001). However, statin therapy was associated with significantly lower event rates only in the intermediate-high- and high-CRP categories (p=0.02 and p=0.008, respectively). Multivariable Cox regression analysis revealed that statin use was independently associated with the primary endpoint only in the high-CRP category (adjusted hazard ratio: 0.64 [95% confidence interval: 0.41–0.98]). Conclusion Statins may exert favorable prognostic effects in patients with PAD and highly elevated CRP levels but not in those with low to moderate CRP levels. Condensed abstract This multicenter retrospective study compared the prognostic effects of statins among patients with peripheral arterial disease (PAD) presenting diverse baseline C-reactive protein (CRP) levels [low CRP (1.0 mg/dL)]. Multivariable analysis showed that statin use was independently associated with a lower rate of death, stroke, myocardial infarction, and major amputation only in the high-CRP category. This suggests that statins may have favorable prognostic effects in patients with PAD and active inflammation.