Abstract 12851: Osteoprotegerin is Associated With Major Bleeding but Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes - Insights From the PLATelet Inhibition and Patient Outcomes (PLATO) Trial

Introduction: Elevated plasma levels of osteoprotegerin (OPG), a secreted cytokine receptor, might be associated with increased cardiovascular (CV) risk. Methods: We measured plasma OPG levels obtained on admission and at 1 month in a pre-defined subset of patients with acute coronary syndromes (ACS) randomized to 6 - 12 months treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial (NCT00391872) . OPG was determined by enzyme immuno-assay. Rates of CV outcomes and major bleeding were presented by baseline OPG quartile groups. The multivariable associations of OPG levels (log transformed) with the composite endpoint of CV death, non-procedural spontaneous myocardial infarction (sMI) or stroke, and with non-CABG major bleeding were assessed with Cox proportional hazards models. Five adjusted models, with co-variates and incremental addition of log transformed biomarkers, were used: 1/ randomized treatment and clinical risk factors (including: age, gender and, hypertension e.g.) 2/ CRP and white blood cell count (WBC), 3/ cystatin C, 4/ hs-Troponin T and NT-proBNP and 5/ growth differentiation factor (GDF)-15. Results: OPG levels were available in 5,135 (28%) patients at baseline, with a median (interquartile interval) of 2.7 (2.0 - 3.6) ng/mL. Event rates of the composite endpoint per increasing quartile group were; 5.2%, 7.5%, 9.2% and 11.9%; and for non-CABG major bleeding: 2.4%, 2.2%, 3.8% and 7.2%. OPG levels at 1 month (n= 3,668), in patients free from any outcome event, were likewise independently associated with bleeding during follow up (n=69); with an adjusted HR of 1.43 (1.04-1.96). There was no interaction between admission OPG levels and randomized treatment. Conclusion: In multivariable analysis, osteoprotegerin was a strong and independent marker of major bleeding but not of ischemic CV events. Thus, OPG seems to provide important independent information on bleeding risk in patients with ACS.