GDF-15 at One Month After an Acute Coronary Syndrome is Associated With Increased Risk of Major Bleeding - A PLATO Biomarker Substudy

Introduction: Levels of Growth Differentiation Factor-15 (GDF-15) are associated with major bleeding events in acute coronary syndromes (ACS), when measured at the time of initial presentation. We hypothesized that an additional measurement of GDF-15 at 1 month after ACS provides additional information regarding risk of major bleeding. Methods: In the PLATO trial, levels of GDF-15 were determined in 4049 ACS patients at both baseline and at 1 month, using an immunoassay (Roche). The primary endpoint was non-CABG related major bleeding. A 1-month landmark analysis was performed, in relation to GDF-15 elevation status at baseline and 1 month, using a cutoff of 1800 ng/L. The relation between GDF-15 at 1 month and the primary endpoint from 1 month onward was evaluated using a Cox proportional hazards model; adjusting for baseline GDF-15, age, anemia (hemoglobin <130 g/L in men, <120 g/L in women), impaired renal function (eGFR <50 mL/min/1.73m2), and history of gastrointestinal bleeding. Results: In the unadjusted analysis, patients with GDF-15 >1800 ng/L at 1 month had increased bleeding rates during follow-up, irrespective of the baseline value. Patients with GDF-15 ≤1800 ng/L at 1 month had lower bleeding risk regardless of initial level (see figure). In the adjusted analysis, GDF-15 >1800 ng/L at 1 month was independently associated with the outcome, hazard ratio 3.39 (95% CI 1.89-6.09). Conclusions: The level of GDF-15 at 1 month after ACS is related to the risk of bleeding during dual antiplatelet treatment. Assessment of GDF-15 level at 1 month provides additional information on the subsequent bleeding risk, regardless of the patient’s index GDF-15 level in the acute phase, and may therefore be helpful for decision-making on continued dual antiplatelet treatment.