The TWILIGHT studies’ findings support the use of ticagrelor in selected high-risk patients as a bleeding-avoidance strategy after percutaneous coronary intervention. That was only one of the many takeaway messages from Saturday’s landmark session on antiplatelet therapy at CRT 2021 Virtual.
Roxana Mehran, MD, of the Icahn School of Medicine at Mount Sinai, presented an overview of the results from TWILIGHT, a prospective, multicenter, blinded, dual-arm study with an enrollment of 9,006 patients from 187 sites across the U.S., Canada, Europe and Asia.
The study, Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT), compared the use of ticagrelor alone versus ticagrelor and aspirin together in high-risk patients 3 months after they underwent percutaneous coronary intervention (PCI) with at least one drug-eluting stent. For the first 3 months after PCI, all patients in the study received dual antiplatelet therapy (DAPT) consisting of ticagrelor and aspirin.
“We wanted to understand balancing the ischemic and bleeding events,” Mehran explained, “and one of the ideas was, ‘Can we withdraw aspirin?’”
While previous studies had explored reducing the duration of aspirin use, “the idea of withdrawing aspirin was something that [had] never [been] done [before] in a double-blind placebo-controlled fashion,” Mehran said.
For physicians looking to implement TWILIGHT’s treatment plan for their own patients, Mehran advised paying special attention to the study’s extensive exclusion criteria. Those excluded from the trial were prior stroke patients, patients who needed chronic oral anticoagulation, and ST-segment elevation myocardial infarction patients, among others.
The trial’s randomization period was 12 months with a 3-month period of observation. At 12 months, the study demonstrated that ticagrelor monotherapy had a lower rate of Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding than ticagrelor-plus-aspirin, 4.0% and 7.1%, respectively, as well as an identical 3.9% rate of death, stroke, and myocardial infarction (MI).
Mehran also presented results from TWILIGHT-ACS, the study’s acute coronary syndrome subgroup, and TWILIGHT-DM, the study’s diabetes mellitus (DM) subgroup.
“If there’s a patient that you want to give a potent agent for as long as possible, it’s that acute coronary syndrome (ACS) patient,” Mehran said.
Within the ACS patient group, the ticagrelor-plus-placebo group had a BARC bleeding rate of 3.6%, while the ticagrelor-plus-aspirin group had a rate of 7.6%. The ticagrelor-plus-aspirin group had a higher incidence of death, stroke and MI at 4.4%, while the ticagrelor-plus-placebo group had a lower rate of 4.3%.
Mehran referenced the TICO Study, which showed similar results in more than 3,000 patients, and noted that the European Society of Cardiology and European Association of Cardio-Thoracic Surgery guidelines give a Class IIA recommendation for ticagrelor monotherapy after 3 months of DAPT (ticagrelor plus aspirin) for ACS patients.
Mehran called the recommendation “extremely significant.”
Physicians are often “incredibly nervous” about withdrawing P2y12 for patients with DM, Mehran said, as they have diffuse disease and tend to possess a significant ischemic burden.
37% of enrolled patients in TWILIGHT had diabetes, and Mehran pointed to the substudy’s finding of a major reduction in bleeding. The rate of death, stroke and MI in the ticagrelor-plus-placebo arm was “numerically lower” than those in the ticagrelor-plus-aspirin group.
While Mehran admitted the study was “clearly underpowered” to say anything definitive about diabetic patients, the observations were nonetheless encouraging. These same trends were also found in patients with chronic kidney disease and those undergoing complex PCI.
Other presenters included Dominick J. Angiolillo, MD, PhD, of the University of Florida College of Medicine, who broke down various strategies to prevent bleeding after PCI, and Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital, Boston who presented on results from the THEMIS study and several other antiplatelet therapy trials.
The THEMIS study was the largest ever done in a diabetic patient pool, according to Bhatt, with a total of 19,220 patients who underwent randomization. The trial, a double-blind, placebo-controlled study, sought to compare the effects of a twice-daily dose of ticagrelor on top of a low-dose of aspirin in diabetic patients with coronary artery disease.
The results were “positive, albeit modestly so,” Bhatt said.
The incidence of cardiovascular death, stroke and MI was lower in the ticagrelor arm (6.9%) than the placebo arm (7.6%), but the rate of Thrombolysis in Myocardial Infarction (TIMI) bleeding was higher (2.2% versus 1.0%, respectively).
In general, Bhatt said, patients with acute coronary syndromes can receive at least 12 months or more of dual antiplatelet therapy (DAPT) if they are at low risk of bleeding. Patients with high bleeding risk can receive as little as 3 months of DAPT and then be switched to monotherapy with ticagrelor, which is preferred, or clopidogrel if cost is a factor.
Bhatt also noted some news that could have gotten lost amid the developments of the coronavirus disease 2019. On June 1, 2020, the U.S. Food and Drug Administration approved the use of ticagrelor to reduce the risk of a first MI or stroke in patients with coronary artery disease.
“A very broad label expansion that goes beyond actually just diabetes,” Bhatt said.