Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR

Javier Escaned; Davide Cao; Usman Baber; Johny Nicolas; Samantha Sartori; Zhongjie Zhang; George Dangas; Dominick J Angiolillo; Carlo Briguori; David J Cohen; Timothy Collier; Dariusz Dudek; Michael Gibson; Robert Gil; Kurt Huber; Upendra Kaul; Ran Kornowski; Mitchell W Krucoff; Vijay Kunadian; Shamir Mehta; David J Moliterno; E Magnus Ohman; Keith G Oldroyd; Gennaro Sardella; Samin K Sharma; Richard Shlofmitz; Giora Weisz; Bernhard Witzenbichler; Stuart Pocock; Roxana Mehran

doi:10.1093/eurheartj/ehab702

Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR

Eur Heart J. 2021 Dec 1;42(45):4624-4634. doi: 10.1093/eurheartj/ehab702.

Authors

Javier Escaned¹, Davide Cao², Usman Baber³, Johny Nicolas², Samantha Sartori², Zhongjie Zhang², George Dangas², Dominick J Angiolillo⁴, Carlo Briguori⁵, David J Cohen^{6

7}, Timothy Collier⁸, Dariusz Dudek⁹, Michael Gibson¹⁰, Robert Gil¹¹, Kurt Huber¹², Upendra Kaul¹³, Ran Kornowski¹⁴, Mitchell W Krucoff¹⁵, Vijay Kunadian¹⁶, Shamir Mehta¹⁷, David J Moliterno¹⁸, E Magnus Ohman¹⁵, Keith G Oldroyd¹⁹, Gennaro Sardella²⁰, Samin K Sharma², Richard Shlofmitz^{6

7}, Giora Weisz²¹, Bernhard Witzenbichler²², Stuart Pocock⁸, Roxana Mehran²

Affiliations

¹ Hospital Clínico San Carlos IDISCC, Complutense University of Madrid, Madrid 28040, Spain.
² The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574, USA.
³ Department of Cardiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
⁴ Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL 32209, USA.
⁵ Mediterranea Cardiocentro, Naples 80122, Italy.
⁶ Cardiovascular Research Foundation, New York, NY 10019, USA.
⁷ St. Francis Hospital, Roslyn, NY 11576, USA.
⁸ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
⁹ Jagiellonian University Medical College, Krakow 31-008, Poland.
¹⁰ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
¹¹ Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw 02-507, Poland.
¹² 3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminen Hospital, Sigmund Freud University, Medical Faculty, Vienna 1160, Austria.
¹³ Batra Hospital and Medical Research Centre, New Delhi 110062, India.
¹⁴ Rabin Medical Center, Petach Tikva 49100, Israel.
¹⁵ Duke University Medical Center-Duke Clinical Research Institute, Durham, NC 27710, USA.
¹⁶ Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University and Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.
¹⁷ Hamilton Health Sciences, Hamilton, ON L8N 3Z5, Canada.
¹⁸ University of Kentucky, Lexington, KY 40506, USA.
¹⁹ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK.
²⁰ Policlinico Umberto I University, Roma 00161, Italy.
²¹ NewYork Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA.
²² Helios Amper-Klinikum, Dachau 85221, Germany.

PMID: 34662382
DOI: 10.1093/eurheartj/ehab702

Abstract

Aims: Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population.

Methods and results: This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status.

Conclusions: Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.

Keywords: ARC-HBR; Aspirin; High bleeding risk; PCI; Ticagrelor monotherapy.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Drug Therapy, Combination
Hemorrhage / chemically induced
Hemorrhage / epidemiology
Humans
Percutaneous Coronary Intervention* / adverse effects
Platelet Aggregation Inhibitors / adverse effects
Ticagrelor / adverse effects
Treatment Outcome

Substances

Platelet Aggregation Inhibitors
Ticagrelor