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Background  Interleukin‐6 ( IL ‐6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome ( ACS ). We aimed to evaluate the prognostic implications of  IL ‐6 post‐ ACS .    Methods and Results   IL ‐6 concentration was assessed at baseline in 4939 subjects in  SOLID ‐ TIMI  52 (Stabilization of Plaque Using Darapladib—Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from  ACS . Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index  ACS ,  ACS  type, and randomized treatment arm. For every  SD  increase in  IL ‐6, there was a 10% higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj  HR ] 1.10, 95% confidence interval [ CI ] 1.01‐1.19) and a 22% higher risk of cardiovascular death or heart failure (adj  HR  1.22, 95%  CI  1.11‐1.34). Patients in the highest  IL ‐6 quartile had a higher risk of major adverse cardiovascular events (adj  HR  Q4:Q1 1.57, 95%  CI  1.22‐2.03) and cardiovascular death or heart failure (adj  HR  2.29, 95%  CI  1.6‐3.29). After further adjustment for biomarkers (high‐sensitivity C‐reactive protein, lipoprotein‐associated phospholipase A 2  activity, high‐sensitivity troponin I, and B‐type natriuretic peptide),  IL ‐6 remained significantly associated with the risk of major adverse cardiovascular events (adj  HR  Q4:Q1 1.43, 95%  CI  1.09‐1.88) and cardiovascular death or heart failure (adj  HR  1.79, 95%  CI  1.22‐2.63).    Conclusions  In patients after  ACS ,  IL ‐6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of  IL ‐6 as a potential therapeutic target in patients with unstable ischemic heart disease.

journal of the american heart association

Interleukin‐6 and the Risk of Adverse Outcomes in Patients After an Acute Coronary Syndrome: Observations From the SOLID‐TIMI 52 (Stabilization of Plaque Using Darapladib—Thrombolysis in Myocardial Infarction 52) Trial