TWILIGHT-HBR suggests ticagrelor monotherapy could lower bleeding risk among patients meeting ARC-HBR criteria. Study presenter Davide Cao, MD, offers further perspective on results of the post hoc analysis.
A post hoc analysis of the TWILIGHT trial is providing clinicians with insight into the effects of ticagrelor monotherapy among patients with high bleeding risk (HBR) from the trial.
Presented at the European Society of Cardiology (ESC) Congress 2021, results suggest ticagrelor monotherapy was associated with a lower risk of BARC 2, 3, or 5 bleeding compared to ticagrelor plus aspirin among patients meeting ARC-HBR criteria.
After identifying 1064 patients from the TWILIGHT trial meeting ARC-HBR criteria, investigates sought to assess the rates of different types of bleeding events among this patient population. Upon analysis, investigators found rates of BARC 2, 3, or 5 bleeding were significantly lower in the ticagrelor monotherapy group compared against ticagrelor plus aspirin in both HBR (6.3% vs 11.4%, P=.004) and non-HBR (3.5% vs 5.9%, P <.0001) patients (P for interaction=.67).
Additionally, in HBR patients, ticagrelor monotherapy was associated with significant reductions in TIMI major bleeding as well as GUSTO moderate or severe bleeding compared to ticagrelor plus aspirin. Investigators also pointed out there was no difference observed in ischemic endpoints from the trial among HBR and non-HBR patients.
For more on the results of this analysis, Practical Cardiology reached out to study investigator Davide Cao, MD, an interventional cardiology fellow at Icahn School of Medicine at Mount Sinai, and a transcription of that conversation can be found below.
Practical Cardiology: Can you describe the results of TWILIGHT HBR?
Davide Cao, MD: Now, the TWILIGHT trial enrolled patients deemed to be at high risk for ischemic and bleeding events. However, the clinical and angiographic criteria that were used to define high-risk patients were developed nearly six years ago and, in the meantime, there have been a number of risk prediction models and risk- or consensus-based definitions that have been proposed to identify high bleeding risk (HBR) patients.
So, the purpose of the present study was to evaluate the treatment effects of ticagrelor monotherapy in a contemporary HBR population, as defined by the Academic Research Consortium criteria, which we know has a consensus-based definition, which identified 14 major criteria 6 minor criteria, and define HBR patients as those who fulfill at least 1 major or 2 minor criteria.
When we applied the ARC criterion HBR, we observed that 17.2% of patients met the ARC-HBR definitions and their results showed that withdrawing aspirin and continuing ticagrelor monotherapy after 3 months of dual antiplatelet therapy among patients who underwent PCI with a drug-eluting stent resulted in a lower incidence of BARC 2, 3, or 5 bleeding as well as BARC 3 or 5 bleeding consistently among HBR and non-HBR patients.
However, as I said, this analysis provided some additional insights. The most important insights are that HBR patients or into the higher-risk profile realized a significantly larger absolute risk reduction with respect to major BARC 3 or 5 bleeding as compared to non-HBR patients. This is particularly important when we evaluate the effectiveness of a new treatment strategy in terms for instance of number needed to treat and the impact on public health is obviously more important when we evaluate what is the absolute reduction in the risk of a patient rather than the relative reduction in the risk of a patient.
Practical Cardiology: We’ve seen multiple subgroup analyses from TWILIGHT, what other analyses could provide additional clinical insight?
Davide Cao, MD: The reason we've run several additional subgroup analyses is because we wanted to focus on patients who are usually underrepresented in clinical trials and they generally tend to be underrepresented because they're at very high risk. In these patients, the level of evidence in support of guideline recommendations is relatively weak. This is the case for HBR patients, diabetic patients, patients with chronic kidney disease, women—all of these groups are largely underrepresented and these were obviously subgroup analyses of particular interest for us.
I would say that there are additional issues to examine from the TWILIGHT trial. I wouldn't name just a specific subgroup of patients, but there are certainly additional issues. An example of one may be examining the total number of bleeding and ischemic events and what are the treatment effects of ticagrelor monotherapy on the overall number of events as compared to a standard time-to-first-event analysis.
Another interesting topic would be the incidence rate of dyspnea among patients treated with ticagrelor. We know that this is reason for ticagrelor discontinuation in about 1 out of 5 patients on ticagrelor. This is, of course, an issue when it comes to patients on ticagrelor monotherapy because if they discontinue ticagrelor because of dyspnea, they don't have background antithrombotic therapy with aspirin. Finally, I would say that another very interesting analysis would be to investigate the tradeoff between ischemic and bleeding events among patients on ticagrelor monotherapy compared ticagrelor plus aspirin and the impact of bleeding and ischemic events on subsequent mortality.
Editor's note: This transcript has been edited for clarity and length.