TWILIGHT: Eliminating Aspirin in Coronary Stent Patients Can Reduce Risk of Multiple Bleeding Events Without Increasing Risk of Heart Attack and Stroke

Principal Investigator: Roxana Mehran, MD, Director of Interventional Cardiovascular Research and Clinical Trials at the Icahn School of Medicine at Mount Sinai

Conference: AHA Scientific Sessions – Featured Science Presentation 

Bottom Line:  Ticagrelor alone after PCI significantly reduced total bleeding events in high-risk patients compared with ticagrelor plus aspirin (the standard treatment), without increasing total adverse cardiac events such as heart attack and stroke.  Ultimately, the study shows that withdrawing aspirin can minimize the bleeding risk, while providing the right amount of ischemic protection. This could lead to a new standard of care for a high-risk patient population.

The primary results of the TWILIGHT trial previously showed that, among high-risk patients undergoing PCI, early aspirin withdrawal followed by ticagrelor monotherapy reduced the occurrence of a first bleeding event without ischemic harm when compared with a prolonged regimen of ticagrelor plus aspirin. In this study, researchers analyzed whether the effects of ticagrelor monotherapy compared with ticagrelor plus aspirin prevent bleeding and adverse cardiac events when total and recurrent events are considered. 

Findings: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy (DAPT) followed by ticagrelor with or without aspirin, recurrent bleeding and ischemic events were infrequent over a 12-month follow-up and withdrawing aspiring reduced bleeding events by roughly 50 percent. Findings demonstrate that ticagrelor monotherapy continues to be more effective than ticagrelor plus aspirin in reducing bleeding. There was no signal of higher ischemic risk with ticagrelor monotherapy when looking at total events. 

Why This Work is Unique/Important: This is a landmark study that specifically focuses on the issue of bleeding with multiple antithrombotic medications and how this impacts adverse events. The findings challenge the standard treatment regimen for PCI patients. 

How Work Was Conducted:  Researchers enrolled 9,006 PCI patients from 187 sites across 11 countries between July 2015 and December 2017.  These patients were given ticragelor 90mg twice daily plus aspirin for three months after the procedure.  

After three months, researchers randomized 7,119 patients to either continue with ticagrelor plus aspirin, or ticagrelor plus placebo (no aspirin).  Researchers analyzed patients with multiple bleeding and/or ischemic events and evaluated the impact of the monotherapy or DAPT on total events. 

Results: 391 patients had at least one bleeding event - 278 were on ticagrelor with aspirin and 148 took ticagrelor with no aspirin. 7.2 percent of the 391 patients had multiple bleeding events, 23 of these patients were in the aspirin group, and six were in the no aspirin group.  Among 272 patients with at least one cardiovascular event (137 vs 135), 13.6 percent of them had multiple events – of these patients, 17 of them were in the aspirin group, and 17 were in the group without aspirin.  

Ultimately, withdrawing aspirin reduced multiple bleeding events by 46 to 50 percent while having no impact on adverse cardiovascular events. 

What Study Means for Clinicians: A growing body of evidence now supports the safety and efficacy of a bleeding-avoidance strategy based on ticagrelor monotherapy after a short course of DAPT.   Findings from this substudy should encourage clinicians to change the present paradigm of prolonged DAPT after PCI, even in high-risk settings.

What Study Means for Patients: Bleeding complications after PCI can impact patient's prognosis just like ischemic events. Aspirin (given with ticagrelor), which is part of the standard treatment for PCI patients is poorly tolerated and often discontinued due to its established gastric toxicity. This study’s findings strongly support removing aspirin and putting patients on tricagrlor monotherapy is an effective bleeding avoidance strategy. This can be safely implemented with no evidence of harm for elderly, frail, and high-risk patients who are at increased risk for bleeding and ischemic complications.

Quotes: “Extending the primary results of the TWILIGHT trial, the current analysis shows that withdrawal of aspirin and continuation of ticagrelor not only prevents index bleeding events, but also recurrent events thereafter,” said Dr. Mehran, who is also a Mount Sinai Professor in Cardiovascular Clinical Research and Outcomes at Icahn Mount Sinai and the global principal investigator of the study. Perhaps more importantly, there was no evidence that ischemic risk was increased with this strategy.”

“These results should motivate greater clinical adoption of ticagrelor monotherapy in many high-risk patients treated with PCI,” adds Usman Baber, MD, Director of the Cardiac Catherization Lab at The University of Oklahoma, and the Chair of the Clinical Coordinating Center for the study.

About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

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