Roxana Mehran, MD, center, principal investigator of the TWILIGHT study, with leading collaborators in the study, from left, Annapoorna S. Kini, MD; Valentin Fuster, MD, PhD; Juan J. Badimon, PhD; George Dangas, MD, PhD; Usman Baber, MD, MS; and Samin K. Sharma, MD.
High-risk patients who have undergone a coronary stent procedure may not require long-term aspirin, according to a groundbreaking global study led by Roxana Mehran, MD, Director of the Center for Interventional Cardiovascular Research and Clinical Trials, Mount Sinai Heart, and the Mount Sinai Professor in Cardiovascular Clinical Research and Outcomes, Icahn School of Medicine at Mount Sinai.
“We showed that withdrawal of aspirin after three months in patients already on ticagrelor, a potent antiplatelet regimen, reduced bleeding significantly without the harm of increasing death or heart attacks,” says Dr. Mehran, global principal investigator of “Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention” (TWILIGHT), which was published in September 2019 in The New England Journal of Medicine.
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 in the United States and around the world on this pioneering clinical trial.”
The study addresses long-standing questions about the treatment of high-risk patients after percutaneous coronary intervention (PCI), also known as angioplasty, which opens blocked arteries and restores normal blood flow to the heart. “The same patients who are at high risk for ischemic events—such as heart attack or stroke caused by blocked blood vessels—are also at high risk for bleeding events,” says Dr. Mehran. “You have to find the right balance in therapies, and it is not easily found.”
In the current standard of care, high-risk patients who have received a cardiac stent are advised to take dual-antiplatelet therapy (DAPT)—both aspirin and a drug from a class of strong antiplatelet medications called P2Y12 inhibitors, of which ticagrelor is one. These two medications prevent heart attack or stroke by reducing the risk of blood clots. DAPT combines two drugs with similar effects, Dr. Mehran says, like using both “a shotgun and slingshot” for self-defense. TWILIGHT examined the impact of taking ticagrelor alone versus ticagrelor plus aspirin on clinically relevant bleeding among high-risk patients.
Investigators enrolled 9,006 patients at 187 sites in the United States, Canada, Europe, and Asia. They were high risk, meaning they met criteria such as having long or complex lesions in coronary arteries, or disorders such as diabetes or chronic kidney disease. All patients had undergone PCI with at least one drug-eluting stent and were prescribed aspirin and ticagrelor. After a three-month course of DAPT, the 7,119 patients without major adverse events were randomized to take either DAPT or ticagrelor with a placebo for 12 months. Among patients who took DAPT, 7.1 percent had major bleeding, compared with 4 percent of those who took ticagrelor and a placebo, and there was no difference in the risk for heart attack, death, or stroke between the groups. “This simpler approach saved many bleeding events and preserved the benefit of the single potent blood thinner,” says Usman Baber, MD, MS, Assistant Professor of Medicine (Cardiology), Icahn School of Medicine, who was lead author of the study with Dr. Mehran, and Chair of the TWILIGHT Clinical Coordinating Center.
The results were corroborated by a sub-study led by Juan J. Badimon, PhD, Professor of Medicine (Cardiology), and Director of Atherothrombosis Research at Mount Sinai Heart. Using a tool he is renowned for developing, the Badimon Chamber, researchers measured the thrombogenicity or “stickiness” of the blood in a group of 42 TWILIGHT patients, testing samples taken before and after they completed the 12-month treatment. Like the clinical study, the study of blood samples found that withdrawing aspirin caused no additional clot formation.
“The findings are particularly important and have the potential to change PCI practice,” says a co-author of the TWILIGHT study, Samin K. Sharma, MD, Director of Clinical and Interventional Cardiology at The Mount Sinai Hospital, and Anandi Lal Sharma Professor of Medicine in Cardiology.
Dr. Mehran expressed profound gratitude to Mount Sinai, which was the global sponsoring organization of TWILIGHT. “This study gives you an idea of the things we are able to do as an institution,” she says, “bringing together all of our resources to answer important questions for physicians and enhance the outcome for patients.”
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 an advisory board member for AstraZeneca in the past, and she and Dr. Baber have received consulting fees from AstraZeneca in the past.
Mount Sinai’s exceptional ratings appeared in the latest NYSDOH report, released in April 2019, on the risk factors associated with PCI at 62 hospitals across New York State. The NYSDOH began publishing PCI safety ratings in 1995, in reports designed to help patients make better decisions about their care based upon a statistical review of each hospital’s data. “Patient safety is our top priority at The Mount Sinai Hospital Catheterization Laboratory,” Dr. Sharma says. “Our efficiency and safety outcomes are unparalleled, and we are very proud of this achievement, which is only possible because of the talented and dedicated interventional cardiology team.”
