Results from the TWILIGHT Study Reported at TCT 2019 and Published Simultaneously in the New England Journal of Medicine

SAN FRANCISCO – September 26, 2019 – New data from the randomized, placebo-controlled TWILIGHT trial found that compared to ticagrelor plus aspirin, ticagrelor monotherapy reduces bleeding events without increasing the risk of death, myocardial infarction, or stroke in high-risk patients who have undergone successful percutaneous coronary intervention (PCI) and completed three months of dual antiplatelet therapy (DAPT).

Findings were reported today at the 31st annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Sponsored by the Cardiovascular Research Foundation (CRF), TCT is the world’s premier educational meeting specializing in interventional cardiovascular medicine. The study was also published simultaneously in the New England Journal of Medicine.

Between July 2015 and December 2017, the study enrolled 9,006 patients whom the treating clinician intended to discharge on ticagrelor plus aspirin upon completion of successful PCI with at least one locally approved drug-eluting stent. Trial inclusion also required the presence of at least one clinical and one angiographic feature associated with a high risk of ischemic or bleeding events.

After completing three months of DAPT, event-free patients were randomized to aspirin or placebo with continuation of ticagrelor for an additional 12 months. A total of 7,119 patients were randomized at 187 sites in 11 countries (23.8% female, 36.8% diabetes mellitus, 64.8% ACS). The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The secondary endpoint was the composite of all-cause death, myocardial infarction, or stroke.

At one year, the incidence of major bleeding was 4.0% for patients randomized to ticagrelor plus placebo and 7.1% among patients who received ticagrelor plus aspirin (HR 0.56, 95% CI 0.45 to 0.68; P<0.001). The relative risk reduction was similar for BARC 3 or 5 bleeding (1.0% vs. 2.0%; HR 0.49, 95% CI 0.33 to 0.74). In addition, rates of all cause death, myocardial infarction, or stroke were 3.9% for both groups (HR 0.99, 95% CI, 0.78 to 1.25; Pnon-inferiority<0.001). The respective rates of all-cause death (1.0% vs. 1.3%), myocardial infarction (2.7% vs. 2.7%) and definite or probable stent thrombosis (0.4% vs. 0.6%) were similar between groups. There were 16 ischemic strokes in the ticagrelor monotherapy group and 8 ischemic strokes in the dual antiplatelet therapy group (0.5% vs. 0.2%). The effect of ticagrelor monotherapy on the key secondary outcome was consistent across pre-defined subgroups.

“Lowering bleeding risk while preserving ischemic benefit is critically important, especially in high risk patients,” said Roxana Mehran, MD, Professor of Medicine at Mount Sinai School of Medicine and Director of Interventional Cardiovascular Research and Clinical Trials at the Zena and Michael A. Wiener Cardiovascular Institute. “This study shows that among high-risk PCI patients who were treated with ticagrelor and aspirin for three months, an antiplatelet strategy of continuing ticagrelor alone, compared with ticagrelor plus aspirin, results in substantially less bleeding without incurring ischemic harm over one year. These results suggest that ticagrelor monotherapy may be a suitable antiplatelet strategy to lower bleeding while preserving ischemic benefit in this group of patients.”

“This landmark study unequivocally shows that withdrawal of aspirin in patients already on ticagrelor and ASA for three months reduces bleeding significantly without incurring harm. This global collaboration with our colleagues was central to achieving the successful completion of this trial. For this I am most grateful. These are important questions for clinicians.”

The TWILIGHT study was designed and sponsored by the Icahn School of Medicine at Mount Sinai and supported by an investigator-initiated grant from AstraZeneca. Dr. Mehran made the following disclosures: Consultant/executive committee/advisory board/personal fees from Abbott Laboratories, Boston Scientific, Medscape, Siemens Medical Solutions, Phillips (Spectranetics), PLx Pharma, Roivant Sciences Inc., Volcano Corporation, Sanofi, and Janssen;   Research funding to institution from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, BMS, CSL Behring, DSI, Medtronic, Boston Scientific, Novartis, and OrbusNeich; Equity <1% from Claret Medical and Elixir Medical; and DSMB membership paid to the institution from Watermark Research Partners.