Results from international clinical trial 'TWILIGHT' could change standard of care for high-risk cases
NEW YORK, Sept. 26, 2019 /PRNewswire-PRWeb/ -- High-risk patients undergoing coronary stent procedures may not require long-term aspirin use after stent placement, Mount Sinai researchers report in a groundbreaking study.
The current standard of care for these patients is to combine aspirin with an anti-clotting medication, such as ticagrelor, to lower the risk of heart attack. However, this treatment also increases bleeding complications, and identifying therapies that lower bleeding without increasing heart attack risk has emerged as a clinical priority.
New results from the study, "Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention" (TWILIGHT), suggest that doctors treat high-risk cardiac patients following percutaneous coronary intervention (PCI) by withdrawing aspirin and using ticagrelor alone. The findings were published in the September 26 issue of The New England Journal of Medicine and presented as a late-breaking trial at the 31st Transcatheter Cardiovascular Therapeutics (TCT), the annual scientific conference of the Cardiovascular Research Foundation.
"This pivotal, first-ever study to withdraw aspirin in complex patients with coronary stents underlines the importance of bleeding avoidance strategies for targeted care. We showed that withdrawal of aspirin after three months in patients already on a potent antiplatelet regimen (ticagrelor) reduced bleeding significantly without the harm of increasing death or heart attacks," said TWILIGHT's Global Principal Investigator, Roxana Mehran, MD, Director of the Center for Interventional Cardiovascular Research and Clinical Trials at Mount Sinai Heart and Professor of Cardiology, and Population Health Science and Policy, at Icahn School of Medicine at Mount Sinai. "This simpler approach saved many bleeding events and preserved the benefit of the single potent blood thinner (ticagrelor). We thank our global investigators in 187 sites around the world who worked tirelessly to bring this study to the finish line, and the patients who agreed to participate in this investigator-sponsored study."
"As an academic, investigator-initiated global trial, this effort represents the concerted and enthusiastic support of partners and collaborators within the United States and abroad who were committed to answering an important and clinically relevant question," says Usman Baber, MD, MS, Chair of the TWILIGHT Clinical Coordinating Center and Assistant Professor of Medicine at the Icahn School of Medicine at Mount Sinai. "The overall magnitude and consistency of effect we observed with ticagrelor monotherapy suggests this may be a safer and effective antiplatelet strategy as compared with standard of care."
Current medical guidelines for patients receiving a cardiac stent in a cardiac catheterization laboratory through a minimally invasive PCI procedure advise that patients receive dual-antiplatelet therapy with both aspirin and a drug from a class of stronger antiplatelet medications called P2Y12 inhibitors, of which ticagrelor is one. These medications prevent blood clots that can lead to heart attack or stroke by reducing the ability of platelets, cellular fragments circulating in the blood, to stick to one another and form a clot. TWILIGHT examined the impact of ticagrelor alone versus ticagrelor plus aspirin on clinically relevant bleeding among patients at high ischemic or bleeding risk undergoing PCI.
The investigators enrolled 9,006 high-risk patients at 187 sites across 11 countries in the United States, Canada, Europe, and Asia. All patients had undergone successful PCI with at least one drug-eluting stent and had been discharged on dual antiplatelet therapy with aspirin and ticagrelor for a three-month duration. After completing the three-month course of dual-antiplatelet therapy, patients without major adverse events were then randomized in a double-blind fashion to either aspirin (81 to 100 mg daily) or placebo, and all patients continued with open-label ticagrelor (90 mg twice daily) for 12 months. Investigators tracked the occurrence of any clinically relevant bleeding, or adverse events such as death, heart attack, and stroke.
For patients who took ticagrelor and no aspirin (placebo), bleeding was reduced by 44 percent, compared to patients on ticagrelor combined with aspirin. Additionally, there were no differences in the risk for heart attack, death, or stroke between the groups, which suggests that aspirin withdrawal does not compromise safety. These results were consistent in both men and women, and in patients older and younger than 65 and those with diabetes (patients over 65 and diabetics are often at higher risk of bleeding and ischemic complications after stenting).
"The TWILIGHT trial is a landmark trial which will change our PCI practice by eliminating aspirin after three months in patients on ticagrelor with resultant lower vascular bleeding and no effect on ischemic endpoints," says Samin K. Sharma, MD, Director of Clinical and Interventional Cardiology for the Mount Sinai Health System. "The findings are particularly important since this is the first study of its kind where a majority of patients were from the United States of America. The results are more generalizable to American patients and the practice of dropping aspirin may be widely and easily accepted in this country."
"This groundbreaking study enhances Mount Sinai Heart's excellence in the field of interventional cardiology," says Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital. "I am proud of our team for achieving such great success with our collaborators here in the United States and around the world on this pioneering clinical trial."
The drug ticagrelor is made by AstraZeneca, which provided Mount Sinai with an unrestricted grant to perform the investigator-initiated study. Dr. Mehran has received financial compensation as a consultant and advisory board member for AstraZeneca in the past. Dr. Baber has received consulting fees from AstraZeneca in the past.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and Mount Sinai South Nassau is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount Sinai South Nassau are ranked regionally.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.