Standard therapy after PCI consists of dual antiplatelet therapy (DAPT) for a year: usually aspirin plus a more powerful anti-clotting drug, such as clopidogrel, ticagrelor or prasugrel. The primary reason these drugs are used is to prevent blood from clotting inside the stent, a condition which, if not alleviated quickly, can cause a heart attack.
Stent thrombosis (ST), as it is called, was the cause for much concern a decade ago with the first-generation drug-eluting stents. Although newer stent designs have reduced the incidence of ST significantly, the use of aspirin plus another anti-clotting drug for one year remains in place, because of the risk of heart attack or death from a blocked stent. In fact the recent DAPT study, previously reported on Angioplasty.Org, looked at whether an even longer period (33 months) was beneficial.
Interestingly, some analyses of the newer drug-eluting stents have shown no significant increase in adverse outcomes for patients who have interrupted or terminated their DAPT after stenting. In fact three years ago, the European regulatory agency gave an indication to Abbott's XIENCE stent for only a three month minimum of DAPT in patients who needed to discontinue use of the drug. In 2013 Medtronic's Resolute stent received the CE Mark approval for a labeling update, stating that stopping after only one month showed no increased risk of stent thrombosis.
The TWILIGHT study will test the current DAPT recommendations from the pharma angle. Most studies of DAPT have used the original antiplatelet drug, clopidogrel (brand name Plavix, which has since gone generic). TWILIGHT asks the question: Is it necessary to use aspirin when the newer antiplatelet agent ticagrelor is on board? The investigators believe that using only ticagrelor will reduce bleeding complications and improve outcomes.
The cohort of high risk patients who are having either elective or urgent PCI will all receive three months of aspirin and ticagrelor. They will then be randomized to continue either on ticagrelor plus aspirin or ticagrelor plus placebo for twelve more months. The study is scheduled to be completed in October 2017.
Mount Sinai Heart Launches Clinical Trial to Test if Coronary Stent Patients Can Avoid Taking Aspirin
August 11, 2015 -- New York -- The Icahn School of Medicine at Mount Sinai has launched an international clinical trial called TWILIGHT to test the safety and effectiveness of treating coronary stent patients with the anti-clotting medication ticagrelor alone, instead of combining it with aspirin, which is the current standard of care. Researchers will analyze the potential benefits of administering ticagrelor to reduce clotting while at the same time reducing the risk of bleeding associated with the use of both medications.
Dr. Roxana Mehran |
"This global study will re-examine the traditional use of dual antiplatelet therapy after coronary artery stenting, and determine whether aspirin can be safely withdrawn," says TWILIGHT's Global Principal Investigator Roxana Mehran, MD, Director of the Office of Interventional Cardiovascular Research and Clinical Trials of Mount Sinai Heart and Professor of Cardiology and Population Health Science and Policy at Icahn School of Medicine at Mount Sinai. "Our research team will determine the effectiveness and safety of ticagrelor alone, compared to using ticagrelor plus aspirin, to reduce the occurrence of bleeding and adverse events after cardiac stenting."
Dr. Samin K. Sharma |
"This clinical trial will test the feasibility of withdrawing aspirin in high-risk patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents," says Samin K. Sharma, MD, Director of Clinical and Interventional Cardiology for the Mount Sinai Health System. "Mount Sinai Heart looks forward to conducting this exciting, large-scale investigation to help improve PCI patient care around the world."
For patients receiving a cardiac stent in a cardiac catheterization laboratory through a minimally invasive PCI procedure, current medical guidelines advise that patients receive dual-antiplatelet therapy (DAPT) with both aspirin and a drug from a class of stronger antiplatelet medications called P2Y12 inhibitors (e.g. ticagrelor). Such 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.
"This innovative clinical trial will provide novel insights on an antiplatelet strategy in high-risk patients that we hypothesize will simultaneously reduce bleeding while maintaining anti-ischemic efficacy, thereby improving net clinical benefit over current standard of care," says Usman Baber, MD, MS, Chair of the TWILIGHT Clinical Coordinating Center and Director of Clinical Biometrics at the Office of Interventional Cardiovascular Research and Clinical Trials at Mount Sinai.
The large clinical trial led by Mount Sinai will enroll up to 9,000 study subjects at 100 sites across the United States, Canada, Europe, South America, and Asia. After three months of being prescribed dual-antiplatelet therapy, patients will be blindly randomized to start receiving either ticagrelor (90mg) plus aspirin (81mg daily) for 12 months, or ticagrelor plus placebo. Researchers will track the occurrence of any clinically relevant bleeding, or adverse events such as mortality, heart attack, and stroke.
Patients eligible to enroll in the clinical trial are those high-risk patients 18 years of age or older who have undergone successful PCI with at least one drug-eluting stent and discharged on DAPT with aspirin and ticagrelor for a three-month duration.
"Mount Sinai Heart looks forward to much success with our collaborators here in the United States and around the world for the launch of this pioneering clinical trial," says Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital. "By partnering together globally, we are advancing the care of patients with coronary artery diseases and the field of interventional cardiology."
The drug ticagrelor is made by AstraZeneca, which is providing funding support for the study. Dr. Roxana Mehran (the Principal Investigator in this study) receives financial compensation as a consultant and advisory board member for AstraZeneca (the study sponsor and manufacturer of the study drug ticagrelor).
To learn more about the TWILIGHT Study, please contact: TWILIGHTStudy@mountsinai.org or visit www.clinicaltrials.gov.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services.from community-based facilities to tertiary and quaternary care.
The System includes approximately 6,100 primary and specialty care physicians; 12 minority-owned free-standing ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. Seven departments at The Mount Sinai Hospital and one at the New York Eye and Ear Infirmary (NYEE) ranked nationally in the top 25 in the 2015-2016 "Best Hospitals" issue of U.S. News & World Report. Mount Sinai's Kravis Children's Hospital also is ranked in seven out of ten pediatric specialties by U.S. News & World Report.
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