Dyspnea-Related Ticagrelor Discontinuation After Percutaneous Coronary Intervention

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

doi:10.1016/j.jcin.2023.08.019

Dyspnea-Related Ticagrelor Discontinuation After Percutaneous Coronary Intervention

JACC Cardiovasc Interv. 2023 Oct 23;16(20):2514-2524. doi: 10.1016/j.jcin.2023.08.019.

Authors

Dominick J Angiolillo¹, Davide Cao², Samantha Sartori³, Usman Baber⁴, George Dangas³, Zhongjie Zhang³, Birgit Vogel³, Vijay Kunadian⁵, Carlo Briguori⁶, David J Cohen⁷, Timothy Collier⁸, Dariusz Dudek⁹, Michael Gibson¹⁰, Robert Gil¹¹, Kurt Huber¹², Upendra Kaul¹³, Ran Kornowski¹⁴, Mitchell W Krucoff¹⁵, Alfonso Ielasi¹⁶, Giulio G Stefanini¹⁷, Carlo A Pivato¹⁷, Shamir Mehta¹⁸, David J Moliterno¹⁹, E Magnus Ohman¹⁵, Javier Escaned²⁰, Gennaro Sardella²¹, Samin K Sharma³, Richard Shlofmitz²², Giora Weisz²³, Bernhard Witzenbichler²⁴, P Gabriel Steg²⁵, Stuart Pocock¹⁰, Roxana Mehran²⁶

Affiliations

¹ Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA.
² The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy.
³ The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁴ Department of Cardiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
⁵ 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.
⁶ Mediterranea Cardiocentro, Naples, Italy.
⁷ Cardiovascular Research Foundation, New York, New York, USA; St. Francis Hospital, Roslyn, Roslyn, New York, USA.
⁸ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
⁹ Jagiellonian University Medical College, Krakow, Poland.
¹⁰ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw, Poland.
¹² 3rd Dept Medicine, Cardiology and Intensive Care Medicine, Wilhelminen Hospital, and Sigmund Freud University, Medical Faculty, Vienna, 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 Istituto Clinico Sant'Ambrogio, Milano, Italy.
¹⁷ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
¹⁸ Hamilton Health Sciences, Hamilton, Ontario, Canada.
¹⁹ University of Kentucky, Lexington, Kentucky, USA.
²⁰ Hospital Clínico San Carlos IDISCC, Complutense University of Madrid, Madrid, Spain.
²¹ Policlinico Umberto I University, Roma, Italy.
²² St. Francis Hospital, Roslyn, Roslyn, New York, USA.
²³ NewYork Presbyterian Hospital, Columbia University Medical Center, New York, New York, USA.
²⁴ Helios Amper-Klinikum, Dachau, Germany.
²⁵ Université de Paris and Assistance Paris-Hôpitaux de Paris, Paris, France.
²⁶ The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: roxana.mehran@mountsinai.org.

PMID: 37879803
DOI: 10.1016/j.jcin.2023.08.019

Abstract

Background: Nearly 20% of patients on ticagrelor experience dyspnea, which may lead to treatment discontinuation in up to one-third of cases.

Objectives: The authors sought to evaluate the incidence, predictors, and outcomes of dyspnea-related ticagrelor discontinuation after percutaneous coronary intervention (PCI).

Methods: In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The occurrence of dyspnea associated with ticagrelor discontinuation was evaluated among all patients enrolled in the trial. A landmark analysis was performed at 3 months after PCI, that is, the time of randomization. Predictors of dyspnea-related ticagrelor discontinuation were obtained from multivariable Cox regression with stepwise selection of candidate variables.

Results: The incidence of dyspnea-related ticagrelor discontinuation was 6.4% and 9.1% at 3 and 15 months after PCI, respectively. Independent predictors included Asian race (lower risk), smoking, prior PCI, hypercholesterolemia, prior coronary artery bypass, peripheral artery disease, obesity, and older age. Among 179 patients who discontinued ticagrelor because of dyspnea after randomization, ticagrelor monotherapy was not associated with a higher risk of subsequent ischemic events (composite of all-cause death, myocardial infarction, or stroke) compared with ticagrelor plus aspirin (5.0% vs 7.1%; P = 0.566).

Conclusions: In the TWILIGHT trial, dyspnea-related ticagrelor discontinuation occurred in almost 1 in 10 patients and tended to occur earlier rather than late after PCI. Several demographic and clinical conditions predicted its occurrence, and their assessment may help identify subjects at risk for therapy nonadherence.

Keywords: PCI; antiplatelet therapy discontinuation; aspirin; dyspnea; ticagrelor monotherapy.

Publication types

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

MeSH terms

Aspirin
Drug Therapy, Combination
Dyspnea / chemically induced
Dyspnea / diagnosis
Dyspnea / drug therapy
Hemorrhage / chemically induced
Humans
Percutaneous Coronary Intervention* / adverse effects
Platelet Aggregation Inhibitors*
Ticagrelor
Treatment Outcome

Substances

Ticagrelor
Platelet Aggregation Inhibitors
Aspirin