This transcript has been edited for clarity.
Saraschandra Vallabhajosyula, MBBS: Hello, and welcome back to the Mayo Clinic Medscape video series. I am Dr Saraschandra Vallabhajosyula, a cardiology fellow at Mayo Clinic. Today we will be discussing the TWILIGHT study, which was recently published in the New England Journal of Medicine. I am joined by my colleague, Dr Patricia Best, who is a consultant interventional cardiologist and an associate professor of medicine at Mayo Clinic. Welcome, Dr Best.
Patricia Best, MD: Thank you.
Vallabhajosyula: TWILIGHT caused quite an impact in clinical practice. Could you tell us about the study?
Best: This study was primarily done by Dr Roxana Mehran and her colleagues. It looked at patients at high risk for thrombotic complications after their percutaneous coronary intervention (PCI) and randomized them to receive dual-antiplatelet therapy (DAPT) therapy with ticagrelor and aspirin or ticagrelor alone. Everyone got DAPT for 3 months and were then randomized, and received 12 more months of one or the other therapies. Their main outcome was bleeding events, but they also focused on ischemic events because they wanted to know whether or not ischemic events were higher when you got rid of the aspirin.
Vallabhajosyula: Can you tell us briefly about the study population and methods?
Best: The study population is always very important, because that will tell you whether or not results are transferable to your patients. The population included patients with high-risk features from a clinical standpoint—patients over the age of 65, women, patients who had troponin-positive acute coronary syndrome (over one third of the patients were in that category), and patients who had non–ST-elevation myocardial infarction (NSTEMI) (about 25% of the population). They also included patients with chronic kidney disease with a glomerular filtration rate < 60 mL/min/1.73 m2.
Patients also had to have one of the higher-risk angiographic features as well, including left main coronary artery disease, proximal left anterior descending coronary artery stenosis, bifurcation stenting (they had to use two stents for the bifurcation disease), very long lesions (such as > 30 mm of stent), or multivessel disease.
By having both of these factors as part of their inclusion criteria, patients were at much higher risk for thrombotic and ischemic complications later. Also, when you look, some of the clinical factors associated with a higher risk for thrombotic complications, such as chronic kidney disease and female sex, also put them at higher risk for bleeding complications.
Vallabhajosyula: That is definitely a very select and an appropriate population. What were the main findings of the study?
Best: The study looked at Bleeding Academic Research Consortium (BARC) 2, 3, and 5 bleeding complications and found a lower risk for bleeding in the patients who had ticagrelor alone in the 3-15 months after their PCI compared with those who had DAPT. Bleeding risk was decreased from 7.1% to 4%, so there was about a 40% reduction in bleeding events, and that was very significant.
In terms of ischemic complications, there was absolutely no difference between the groups. Ticagrelor alone was not inferior to DAPT. In the trial design, they did not randomize patients until after the 3 months; they had to successfully make it through 3 months without major complications, so it is excluding those patients as well.
Where Does TWILIGHT Fit?
Vallabhajosyula: Those are obviously important findings. How do you contextualize these results to our patient populations? And in light of prior studies, where does the study fit in?
Best: Prior studies, such as Smart-Choice and Smart-DATE, looked at lower-risk populations. They also were not necessarily looking at ticagrelor as the second agent in the DAPT, so it could be any agent. They again looked at dropping the DAPT at 3 months. In those studies, it also looked like it was favorable to use a single agent.
Global Leaders was a larger study done in a mixed population, so there were some patients with NSTEMI as well as patients undergoing routine PCI. It dropped the DAPT at 1 month, again used ticagrelor, and evaluated outcomes at 24 months. The study looked for superiority of ticagrelor over DAPT and found a negative outcome. Importantly, compliance with ticagrelor was actually much lower—in the 70% range, versus the 90% range for aspirin. One of the downsides to ticagrelor is that it is a twice-a-day agent.
Vallabhajosyula: These are very interesting observations. How do you see this study in light of prior studies influencing our practice in the cath lab and in the clinic?
Best: It is showing us that in both lower-risk and now higher-risk populations, we can safely remove the aspirin after 3 months of DAPT and leave patients on a single agent, particularly when ticagrelor is being used and there is good compliance. It will lower the bleeding risk, which is expected. However, we do not know yet some about some of the higher-risk populations that were excluded from the TWILIGHT study, such as STEMI and cardiogenic shock.
We need to be careful not to extrapolate the findings to patients who have not been studied yet. We want to think about what is safest for our patients, because better understanding the patient's bleeding risk versus their thrombotic risk and tailoring individually to patients will be helpful. I think more patients will be on a single antiplatelet agent at 3 months after their PCI because of this study.
Vallabhajosyula: What are the limitations and caveats of this study that you think are fertile ground for future research?
Best: The fertile ground would be looking at whether we need 3 months of DAPT. When you look at DAPT, that is how all of the original PCI and bare-metal stent studies were done, and maintaining aspirin as part of it. The question is, do we need aspirin early on? Given the very powerful antiplatelet agents we now have available, is aspirin adding any benefit or just adding to the bleeding risk? We do not know some of those data.
Other potential research would be to study whether or not we can switch from ticagrelor to other agents. Although ticagrelor is very beneficial in preventing thrombotic events and ischemic events, it is a twice-a-day agent, and we know that compliance goes down dramatically when you go from once-a-day dosing to twice-a-day dosing. It also has the risk for shortness of breath, which is obviously not an ideal side effect to have in our patient population. Cost is the other factor.
Vallabhajosyula: Dr Best, thank you for your excellent thoughts and sharing such amazing insights into this important study. Thank you for joining us today on theheart.org | Medscape Cardiology.
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Cite this: Entering the TWILIGHT Zone of DAPT Duration - Medscape - Jan 21, 2020.