Ticagrelor With or Without Aspirin in High-Risk Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention

J Am Coll Cardiol. 2020 May 19;75(19):2403-2413. doi: 10.1016/j.jacc.2020.03.008. Epub 2020 Mar 30.


Background: P2Y12 inhibitor monotherapy with ticagrelor after a brief period of dual antiplatelet therapy can reduce bleeding without increasing ischemic harm after percutaneous coronary intervention (PCI). The impact of this approach among patients with diabetes mellitus (DM) remains unknown.

Objectives: The purpose of this study was to examine the effect of ticagrelor monotherapy versus ticagrelor plus aspirin among patients with DM undergoing PCI.

Methods: This was a pre-specified analysis of the DM cohort in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial. After 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The primary endpoint was Bleeding Academic Research Consortium 2, 3, or 5 bleeding. The composite ischemic endpoint was all-cause death, myocardial infarction, or stroke.

Results: Patients with DM comprised 37% (n = 2,620) of the randomized cohort and were characterized by more frequent comorbidities and a higher prevalence of multivessel disease. The incidence of Bleeding Academic Research Consortium 2, 3, or 5 bleeding was 4.5% and 6.7% among patients with DM randomized to ticagrelor plus placebo versus ticagrelor plus aspirin (hazard ratio: 0.65; 95% confidence interval: 0.47 to 0.91; p = 0.012). Ticagrelor monotherapy was not associated with an increase in ischemic events compared with ticagrelor plus aspirin (4.6% vs. 5.9%; hazard ratio: 0.77; 95% confidence interval: 0.55 to 1.09; p = 0.14). In the overall trial population, there was no significant interaction between DM status and treatment group for the primary bleeding or ischemic endpoints.

Conclusions: Compared with ticagrelor plus aspirin, the effect of ticagrelor monotherapy in reducing the risk of clinically relevant bleeding without any increase in ischemic events was consistent among patients with or without DM undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

Keywords: aspirin; bleeding; diabetes mellitus; thrombosis; ticagrelor monotherapy.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / surgery*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Percutaneous Coronary Intervention / adverse effects
  • Percutaneous Coronary Intervention / trends*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Postoperative Complications / chemically induced
  • Postoperative Complications / epidemiology
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Risk Factors
  • Ticagrelor / administration & dosage*
  • Ticagrelor / adverse effects


  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Ticagrelor
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT02270242