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A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
07:40

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

[Clopidogrel plus acetylsalicylic acid: a deadly combination]

Gerard A Rongen1

  • 1UMC St Radboud, afd. Farmacologie-Toxicologie, Nijmegen, the Netherlands. g.rongen@pharmtox.umcn.nl

Nederlands Tijdschrift Voor Geneeskunde
|June 20, 2013
PubMed

Insights

Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in patients with lacunar cerebral infarcts and coronary atherosclerosis. This combination therapy should be discontinued due to lethal toxicity and bleeding risks.

Area of Science:

  • Cardiology
  • Neurology
  • Pharmacology

Background:

  • The SPS3 trial indicated increased mortality with clopidogrel plus aspirin versus aspirin alone in lacunar infarct patients.
  • Dual-antiplatelet therapy (DAPT) is commonly used, but its safety profile requires ongoing evaluation.

Purpose of the Study:

  • To review trial data on clopidogrel/aspirin DAPT, considering between-trial variations in mortality.
  • To investigate the potential 'off-target' lethal toxicity of clopidogrel/aspirin combination therapy.

Main Methods:

  • Meta-analysis of available trial data on clopidogrel/aspirin therapy.
  • Comparative analysis of mortality rates across different control groups in relevant trials.

Main Results:

  • Clopidogrel plus aspirin demonstrated lethal toxicity in patients with lacunar cerebral infarcts and coronary atherosclerosis.
  • An alternative P2Y12 antagonist showed a survival benefit over clopidogrel, suggesting an 'off-target' effect of clopidogrel/aspirin.

Conclusions:

  • The clopidogrel/aspirin combination therapy is associated with increased mortality and serious bleeding complications.
  • Discontinuation of clopidogrel in combination with aspirin is recommended; future trials should evaluate alternative P2Y12 antagonists.

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