TWILIGHT sub-study: same outcomes for diabetes patients

A pre-specified sub-analysis of the TWILIGHT trial demonstrated that participants with diabetes mellitus (DM) who had had a recent percutaneous coronary intervention (PCI) did not differ in death, myocardial infarction (MI), or stroke between the arms (i.e. ticagrelor with either aspirin or placebo) when compared with participants who were not diabetic.

The parent TWILIGHT trial took patients who had just undergone PCI and treated them with ticagrelor plus aspirin for 3 months and, if event-free and adherent, randomly assigned them to ticagrelor plus aspirin or plus placebo for an additional 12 months. The main conclusion of that trial was that dropping aspirin after 3 months of dual antiplatelet therapy (DAPT) following PCI among high-risk patients was associated with lower rates of bleeding but no increased risk of death, MI, or stroke.

The current sub-analysis asked whether those findings hold true for the patients in that cohort who also had DM. Prof. Dominick Angiolillo (University of Florida – Jacksonville, USA) presented the findings of the TWILIGHT-DM sub-study [1]. The results were simultaneously published online in the Journal of the American College of Cardiology [2]. TWILIGHT participants with DM comprised 37% (n=2,620; mean age 64.8 years) of the randomised cohort. They had more comorbidities and a higher prevalence of multivessel disease when compared to non-diabetic patients (n=4,499) randomised in that cohort.

At 1-year follow-up, no significant interaction was found for the primary endpoint when compared with non-diabetic patients (P=0.23). Patients with DM had a higher rate of bleeding in the ticagrelor + aspirin arm, similar to the parent study. The incidence of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding was 4.5% in the ticagrelor + placebo group and 6.7% in the ticagrelor + aspirin group among patients with DM (HR 0.65; 95% CI 0.47-0.91; P=0.012). DM patients assigned to ticagrelor monotherapy also had significant reductions in other bleeding definitions: BARC 3 or 5 (1.1% vs 1.3%), Thrombolysis in Myocardial Infarction (TIMI) minor or major (4.5% vs 6.7%), Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) moderate-to-severe (0.7% vs 2.3%), and International Society on Thrombosis and Haemostasis (ISTH) major (1.4% vs 3.1%). The interaction was positive only for GUSTO bleeding (P=0.03).

Also similar to the parent study, although the ticagrelor monotherapy was associated with numerically fewer all-cause death, MI, or stroke events compared with ticagrelor + aspirin, these data did not reach statistical significance (4.6% vs 5.9%; HR 0.77; 95% CI 0.55 to 1.09; P=0.14; P for interaction=0.05).

In conclusion, this sub-analysis shows consistency with the overall trial and that dropping aspirin after 3 months from PCI reduces bleeding.

1. 1. Angiolillo D, et al. Abstract 410-16, ACC/WCC 28-30 March 2020.
   2. Angiolillo DJ, et al. Am Coll Cardiol. 2020. DOI:1016/j.jacc.2020.03.008.

Posted on 8 September, 20205 August, 2021