Gastrointestinal adverse events after dual antiplatelet therapy: clopidogrel is safer than ticagrelor, but prasugrel data are lacking or inconclusive

Cardiology. 2013;126(1):35-40. doi: 10.1159/000350961. Epub 2013 Jul 12.


Current guidelines offer a choice of P2Y12 receptor antagonist among clopidogrel, prasugrel or ticagrelor on top of aspirin (ASA) for dual antiplatelet therapy (DAPT) in patients after acute coronary syndromes (ACS). However, the comparative risks of gastrointestinal (GI) adverse events during DAPT are not clear. Two large ACS trials (TRITON and PLATO) provide a valuable opportunity to directly match the risks of GI complications among current antiplatelet regimens. We compared the rates of GI adverse events after prasugrel and ticagrelor versus clopidogrel based on the Food and Drug Administration (FDA) clinical safety reviews. When compared with ticagrelor, clopidogrel is safer with regard to GI-related risks including fewer overall GI/anal bleeding events and spontaneous GI hemorrhagic episodes, less nausea, vomiting, dyspepsia and diarrhea, and a lower rate of presence of Helicobacter pylori. Among GI symptoms, only constipation was more common after clopidogrel than following ticagrelor. There were extrahepatic risks observed with ticagrelor but not with prasugrel when compared to clopidogrel. Prasugrel unquestionably caused more bleeding from the GI tract and GI malignancies than clopidogrel. However, the entire spectrum of GI effects of prasugrel is much less well known and mostly based on sponsor analysis rather than FDA-verified numbers. Among 3 DAPT options on top of ASA, clopidogrel seems to represent the safest alternative, although comprehensive data on direct prasugrel-associated GI effects are lacking or inconclusive.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy
  • Adenosine / adverse effects
  • Adenosine / analogs & derivatives
  • Aspirin / adverse effects
  • Chemical and Drug Induced Liver Injury / etiology
  • Clinical Trials, Phase III as Topic
  • Clopidogrel
  • Double-Blind Method
  • Female
  • Gastrointestinal Hemorrhage / chemically induced*
  • Gastrointestinal Neoplasms / chemically induced*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Multicenter Studies as Topic
  • Piperazines / adverse effects
  • Platelet Aggregation Inhibitors / adverse effects*
  • Prasugrel Hydrochloride
  • Purinergic P2Y Receptor Antagonists / adverse effects*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Thiophenes / adverse effects
  • Ticagrelor
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives


  • Piperazines
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Thiophenes
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine
  • Ticlopidine
  • Aspirin