Growth Differentiation Factor 15 at 1 Month After an Acute Coronary Syndrome Is Associated With Increased Risk of Major Bleeding

J Am Heart Assoc. 2017 Apr 14;6(4):e005580. doi: 10.1161/JAHA.117.005580.

Abstract

Background: Growth differentiation factor-15 (GDF-15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether follow-up measurements provide additional information. The objective of this study was to investigate whether GDF-15 measured 1 month after an ACS provides additional information beyond the baseline levels with regard to the risk of major bleeding.

Methods and results: GDF-15 was measured at baseline and at 1 month after an ACS in 4049 patients included in the PLATelet inhibition and patient Outcomes (PLATO) trial. The association between 1-month GDF-15 level and non-coronary artery bypass grafting surgery-related major bleeding was assessed by a multivariable Cox model, adjusting for baseline GDF-15, age, anemia, impaired renal function, history of gastrointestinal bleeding, and sex. Elevated GDF-15 (>1800 ng/L) at 1 month was associated with an increased risk of non-coronary artery bypass grafting-related major bleeding (3.9% versus 1.2%; hazard ratio, 3.38; 95% CI, 1.89-6.06), independent of baseline GDF-15. Patients who had elevated GDF-15 levels at baseline and subsequent nonelevated GDF-15 at 1 month had a similar risk as patients who had nonelevated levels at both measurements.

Conclusions: GDF-15 at 1 month after an ACS is related to the risk of bleeding during DAPT and provides additional information on the bleeding risk beyond baseline GDF-15 levels. GDF-15 levels may therefore be useful as part of decision support concerning long-term antithrombotic treatment in patients post-ACS.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Keywords: biomarker; bleeding; ischemic heart disease.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / drug therapy*
  • Adenosine / adverse effects
  • Adenosine / analogs & derivatives*
  • Aged
  • Aspirin / adverse effects*
  • Biomarkers / blood
  • Clopidogrel
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Growth Differentiation Factor 15 / blood*
  • Hemorrhage / blood
  • Hemorrhage / chemically induced*
  • Hemorrhage / diagnosis
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Platelet Aggregation Inhibitors / adverse effects*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Ticagrelor
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticagrelor
  • Adenosine
  • Ticlopidine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00391872