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 A2 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.
Bibliographical noteFunding Information:
The SOLID-TIMI 52 trial was supported by a research grant from GlaxoSmithKline. Reagent support was provided by Singulex (IL-6) and Abbott Laboratories (hsTnI, BNP).
outside the submitted work, Dr Braunwald reports grant support to his institution from Duke University, Merck, AstraZeneca, Novartis, and Daiichi Sankyo; personal fees for consultancies with The Medicines Company and Theravance; personal fees for lectures from Medscape and Menarini International; uncompensated consultancies and lectures from Merck and Novartis. Dr O’Donoghue reports research grants from Amgen, the Medicines Company, AstraZeneca, Eisai, GlaxoSmithKline, Merck, and Janssen. The remaining authors have no disclosures to report.
Dr Morrow reports grants to the TIMI Study Group from Abbott Laboratories, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GlaxoSmithKline, Merck, Novartis, Roche Diagnostics, and Singulex, and consultant fees from Abbott Laboratories, AstraZeneca, diaDexus, GlaxoSmithKline, Merck, Peloton, Roche Diagnostics, and Verseon. Dr Cannon reports research grants from Amgen, Arisaph, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Merck, and Takeda, and consulting fees from Alnylam, Amgen, Arisaph, AstraZe-neca, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Kowa, Lipimedix, Merck, Pfizer, Regeneron, Sanofi, and Takeda. Dr Jarolim has received research support through his institution from Abbott Laboratories, AstraZe-neca, Daiichi-Sankyo, Inc, GlaxoSmithKline, Janssen Scientific Affairs, LLC, Merck, Roche Diagnostics Corporation, Takeda Global Research and Development Center, and Waters Technologies Corporation. Dr Lukas is an employee at GlaxoSmithKline. Dr Hochman is principal investigator for the ISCHEMIA trial for which, in addition to support by National Heart, Lung, and Blood Institute, there are in-kind donations from Abbott Vascular, Medtronic, Inc, St Jude Medical, Inc, Volcano Corporation, Arbor Pharmaceuticals, AstraZeneca Pharmaceuticals, Merck, Omron Healthcare, Inc, and financial donations from Arbor Pharmaceuticals, LLC and AstraZeneca Pharmaceuticals. Dr Braunwald reports grant support to his institution from GlaxoSmithKline. For work
- Acute coronary syndrome
- Vascular biology