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

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.