Impact of Age on the Safety and Efficacy of Ticagrelor Monotherapy in Patients Undergoing PCI

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

doi:10.1016/j.jcin.2021.04.043

Impact of Age on the Safety and Efficacy of Ticagrelor Monotherapy in Patients Undergoing PCI

JACC Cardiovasc Interv. 2021 Jul 12;14(13):1434-1446. doi: 10.1016/j.jcin.2021.04.043.

Authors

Dominick J Angiolillo¹, Davide Cao², Usman Baber³, Samantha Sartori², Zhongjie Zhang², George Dangas², Shamir Mehta⁴, Carlo Briguori⁵, David J Cohen⁶, Timothy Collier⁷, Dariusz Dudek⁸, Javier Escaned⁹, C Michael Gibson¹⁰, Robert Gil¹¹, Kurt Huber¹², Upendra Kaul¹³, Ran Kornowski¹⁴, Mitchell W Krucoff¹⁵, Vijay Kunadian¹⁶, David J Moliterno¹⁷, E Magnus Ohman¹⁵, Keith Oldroyd¹⁸, Gennaro Sardella¹⁹, Samin K Sharma², Richard Shlofmitz²⁰, Giora Weisz²¹, Bernhard Witzenbichler²², Stuart Pocock⁷, Roxana Mehran²³

Affiliations

¹ University of Florida College of Medicine, Jacksonville, Florida, USA.
² The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, New York, New York, USA.
³ The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
⁴ Hamilton Health Sciences, Hamilton, Ontario, Canada.
⁵ Mediterranea Cardiocentro, Naples, Italy.
⁶ University of Missouri-Kansas City, Kansas City, Missouri, USA.
⁷ London School of Hygiene and Tropical Medicine, London, United Kingdom.
⁸ Jagiellonian University Medical College, Krakow, Poland.
⁹ Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos and Complutense University, Madrid, Spain.
¹⁰ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
¹¹ Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw, Poland.
¹² Wilhelminenspital, Wien, Austria.
¹³ Batra Hospital and Medical Research Centre, New Delhi, India.
¹⁴ Rabin Medical Center, Petach Tikva, Israel.
¹⁵ Duke University Medical Center-Duke Clinical Research Institute, Durham, North Carolina, 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, United Kingdom.
¹⁷ University of Kentucky, Lexington, Kentucky, USA.
¹⁸ The West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, United Kingdom.
¹⁹ Policlinico Umberto I University, Rome, Italy.
²⁰ St. Francis Hospital, Roslyn, Roslyn, New York, USA.
²¹ NewYork-Presbyterian Hospital, Columbia University Medical Center, New York, USA.
²² Helios Amper-Klinikum, Dachau, Germany.
²³ The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, New York, New York, USA. Electronic address: roxana.mehran@mountsinai.org.

PMID: 34238553
DOI: 10.1016/j.jcin.2021.04.043

Abstract

Objectives: The aim of this study was to assess the impact of age on the safety and efficacy of ticagrelor monotherapy after percutaneous coronary intervention (PCI).

Background: As the risk for bleeding and ischemic complications after PCI increases with age, the authors conducted a pre-specified analysis of the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial to evaluate the possible benefits of ticagrelor monotherapy according to age.

Methods: The TWILIGHT trial enrolled patients undergoing PCI with drug-eluting stents who fulfilled at least 1 clinical and 1 angiographic high-risk criterion. Age ≥65 years was a clinical entry criterion. After 3 months of dual-antiplatelet therapy with ticagrelor, event-free patients were randomized to ticagrelor plus placebo or ticagrelor plus aspirin for an additional 12 months. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding. The key secondary endpoint was the composite of all-cause death, myocardial infarction, or stroke.

Results: A total of 3,113 patients (47.7%) were ≥65 years of age. At 1 year after randomization, ticagrelor monotherapy significantly reduced BARC type 2, 3, or 5 bleeding (4.5% vs. 8.2%; hazard ratio: 0.53; 95% confidence interval: 0.40 to 0.71) without increasing ischemic events (4.2% vs. 4.4%; hazard ratio: 0.96; 95% confidence interval: 0.68 to 1.35) compared with ticagrelor plus aspirin among patients ≥65 years of age. These findings were consistent in patients <65 years of age with respect to the primary (p_interaction = 0.62) and key secondary (p_interaction = 0.77) endpoints and across different age categories.

Conclusions: A strategy of ticagrelor monotherapy following 3 months of dual-antiplatelet therapy significantly reduced clinically relevant bleeding compared with ticagrelor plus aspirin without an increase in ischemic events, irrespective of age.

Keywords: PCI; age; bleeding; thrombosis; ticagrelor monotherapy.

Publication types

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

MeSH terms

Age Factors
Aged
Aspirin / adverse effects
Drug Therapy, Combination
Humans
Percutaneous Coronary Intervention*
Platelet Aggregation Inhibitors / adverse effects
Ticagrelor* / adverse effects
Treatment Outcome

Substances

Platelet Aggregation Inhibitors
Ticagrelor
Aspirin