Prediction of high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndromes

Int J Cardiol. 2017 Aug 1:240:60-65. doi: 10.1016/j.ijcard.2017.03.074. Epub 2017 Mar 18.

Abstract

Background: About 40% of clopidogrel-treated patients display high platelet reactivity (HPR). Alternative treatments of HPR patients, identified by platelet function tests, failed to improve their clinical outcomes in large randomized clinical trials. A more appealing alternative would be to identify HPR patients a priori, based on the presence/absence of demographic, clinical and genetic factors that affect PR. Due to the complexity and multiplicity of these factors, traditional statistical methods (TSMs) fail to identify a priori HPR patients accurately. The objective was to test whether Artificial Neural Networks (ANNs) or other Machine Learning Systems (MLSs), which use algorithms to extract model-like 'structure' information from a given set of data, accurately predict platelet reactivity (PR) in clopidogrel-treated patients.

Methods: A complete set of fifty-nine demographic, clinical, genetic data was available of 603 patients with acute coronary syndromes enrolled in the prospective GEPRESS study, which showed that HPR after 1month of clopidogrel treatment independently predicted adverse cardiovascular events in patients with Syntax Score >14. Data were analysed by MLSs and TSMs. ANNs identified more variables associated PR at 1month, compared to TSMs.

Results: ANNs overall accuracy in predicting PR, although superior to other MLSs was 63% (95% CI 59-66). PR phenotype changed in both directions in 35% of patients across the 3 time points tested (before PCI, at hospital discharge and at 1month).

Conclusions: Despite their ability to analyse very complex non-linear phenomena, ANNs or MLS were unable to predict PR accurately, likely because PR is a highly unstable phenotype.

Keywords: Antiplatelet therapy; Artificial neural networks; Clopidogrel; Platelet reactivity; VASP.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / genetics*
  • Aged
  • Clopidogrel
  • Female
  • Gene Regulatory Networks / drug effects
  • Gene Regulatory Networks / physiology
  • Humans
  • Machine Learning*
  • Male
  • Middle Aged
  • Neural Networks, Computer*
  • Platelet Activation / drug effects*
  • Platelet Activation / physiology
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Predictive Value of Tests
  • Prospective Studies
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine