Ticagrelor was discontinued due to dyspnea in nearly 1 in 10 patients in the TWILIGHT trial, and this happened earlier after percutaneous coronary intervention (PCI), according to a post hoc analysis of the trial. This information was reported by Dominick J. Angiolillo, MD, PhD, of the University of Florida College of Medicine, Jacksonville; Davide Cao, MD, of the Icahn School of Medicine at Mount Sinai, New York, and Humanitas University, Pieves Emanuele, Italy, and colleagues in a manuscript published Monday online and in the Oct. 23 issue of JACC: Cardiovascular Interventions. Patients are at greater risk for cardiovascular events when they do not adhere to their antiplatelet therapy regimens. Ticagrelor, a P2Y12 inhibitor, has been used with aspirin as a form of management post-PCI. About 20% of patients taking ticagrelor experience dyspnea, though results have varied on dosage and clinical settings. The TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial compared patients taking ticagrelor plus aspirin with patients taking ticagrelor monotherapy after 3 months of dual antiplatelet therapy (DAPT). These patients all underwent PCI with a drug-eluting stent and were considered to be at high risk for both ischemia and bleeding post-PCI. The ticagrelor monotherapy patients had a significant reduction in bleeding, with no difference in thrombotic events when compared to patients on DAPT at 1-year post-PCI, but dyspnea-related discontinuation of ticagrelor was prominent in patients on the monotherapy. This analysis evaluated the rates and predictors of dyspnea in patients in the TWILIGHT trial post-PCI. All patients in the TWILIGHT trial were evaluated for dyspnea-related discontinuation of post-PCI antiplatelet therapy. The trial enrolled 9,006 patients. , The rate of dyspnea-related ticagrelor discontinuation was 6.4% at 3 months post-PCI and 9.1% at 15 months. Compared to patients who did not report dyspnea, patients who experienced dyspnea were older (67.9 ± 9.5 years vs. 64.4 ±10.2 years), more likely to be white (88.6% vs. 69.1%), less likely to be Asian (5.5% vs. 24.4%), had higher body mass index (30.2 ± 5.8 kg/m2 vs. 28.6 ± 5.6 kg/m2), more likely to have enrolled in North America (69.1% vs. 43.3%) and less likely to have enrolled in Asia (4.2% vs. 22.2%). Patients experiencing dyspnea also were more likely to be non-smokers (60% vs. 53.3%) and have hypercholesterolemia (78.3% vs. 61.1%), hypertension (80% vs. 72.8%), peripheral arterial disease (12.2% vs. 7.5%), previously undergone PCI (53.4% vs. 42.7%) and previously undergone coronary artery bypass grafting (18.8% vs. 10.6%), Risk of subsequent ischemic events (the composite of all-cause death, myocardial infarction, stroke) was not higher among the patients who discontinued ticagrelor monotherapy compared with the ticagrelor plus aspirin patients (5.0% versus 7.1%; p=0.566). The investigators noted a few limitations of this study. First, the design of the study was a post-hoc analysis. Second, both groups in the study received ticagrelor, so the dyspnea and association with the study drug was reported according to the investigator’s clinical assessment. Finally, clinical endpoints in this analysis were likely underpowered, so the study should be considered hypothesis-generating and exploratory. Overall, discontinuation of ticagrelor due to dyspnea was observed in 9.1% of patients enrolled in the TWILIGHT trial, and several other demographic and clinical conditions may be worth assessing in terms of who is at higher risk for dyspnea. Future studies are needed to prospectively confirm the findings of this research, the investigators wrote. In an accompanying editorial, Gwangsil Kim, MD, of the Inje University College of Medicine, Seoul, South Korea, and CPC Clinical Research, Aurora, Colorado, and Christopher P. Cannon, MD, of CPC Clinical Research and Brigham and Women’s Hospital and Harvard Medical School, Boston, commented on the background of P2Y12 inhibitors and the differences in currently available antiplatelet therapies. The editorialists noted the characteristics of ticagrelor-induced dyspnea, such as the early onset post-initial treatment, dose-dependent tendencies and the mild-to-moderate intensity of the condition. “In real-world data, early discontinuation of ticagrelor was not linked to detrimental cardiovascular events. Although most episodes are reported as mild or transient, sometimes they lead to drug discontinuation,” Kim and Cannon wrote. The editorialists highlighted the demographic and clinical risk factors revealed in this present study but noted the limitations—such as the study covering a very broad range of patients, and the lack of safety and efficacy outcomes—necessitating further research. “Future studies could investigate the diagnostic and treatment options for ticagrelor-induced dyspnea. One of the next issues is how to change ticagrelor to other agents in high-risk patients in the situation of premature ticagrelor discontinuation and the optimal duration,” concluded the editorialists. Sources: Angiolillo DJ, Cao D, Sartori S, et al. Dyspnea-Related Ticagrelor Discontinuation After Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2023;16:2514-2524. Kim G, Cannon CP. Ticagrelor-Induced Dyspnea: A Controllable Side Effect. JACC Cardiovasc Interv. 2023;16:2525-2527. Image Credit: luchschenF – stock.adobe.com