Comparative Methodological Assessment of the Randomized GLOBAL LEADERS Trial Using Total Ischemic and Bleeding Events. Issue 8 (August 2020)

• Record Type: Journal Article
• Authors: Hara, Hironori; van Klaveren, David; Takahashi, Kuniaki; Kogame, Norihiro; Chichareon, Ply; Modolo, Rodrigo; Tomaniak, Mariusz; Ono, Masafumi; Kawashima, Hideyuki; Wang, Rutao; Gao, Chao; Niethammer, Margit; Fontos, Geza; Angioi, Michael; Ribeiro, Vasco Gama; Barbato, Emanuele; Leandro, Sergio; Hamm, Christian; Valgimigli, Marco; Windecker, Stephan; Jüni, Peter; Steg, Philippe Gabriel; Verbeeck, Johan; Tijssen, Jan G.P.; Sharif, Faisal; Onuma, Yoshinobu; Serruys, Patrick W.
• Is Part Of: Circulation. Volume 13:Issue 8(2020)
• Publication Date: 2020-08
• Subjects: aspirin -- mortality -- myocardial infarction -- percutaneous coronary intervention -- ticagrelor; Cardiovascular system -- Diseases -- Treatment -- Periodicals; Cardiovascular system -- Diseases -- Research -- Periodicals; Outcome assessment (Medical care) -- Periodicals; Evidence-based medicine -- Periodicals; 616.1007
• DOI: 10.1161/CIRCOUTCOMES.120.006660
• Languages: English
• ISSNs: 1941-7713

Abstract

Abstract : Background: Time-to-first-event analysis considers only the first event irrespective of its severity. There are several methods to assess trial outcomes beyond time-to-first-event analysis, such as analyzing total events and ranking outcomes. In the GLOBAL LEADERS study, time-to-first-event analysis did not show superiority of ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention to conventional 12-month DAPT followed by aspirin monotherapy in the reduction of the primary composite end point of all-cause mortality or new Q-wave myocardial infarction. This study sought to explore various analytical approaches in assessing total ischemic and bleeding events after percutaneous coronary intervention in the GLOBAL LEADERS study. Methods and Results: Total ischemic and bleeding events were defined as all-cause mortality, any stroke, any myocardial infarction, any revascularization, or Bleeding Academic Research Consortium grade 2 or 3 bleeding. We used various analytical approaches to analyze the benefit of ticagrelor monotherapy over conventional DAPT. For ischemic and bleeding events at 2 years after percutaneous coronary intervention, ticagrelor monotherapy demonstrated a 6% risk reduction, compared with conventional 12-month DAPT in time-to-first-event analysis (hazard ratio, 0.94 [95% CI, 0.88–1.01]; log-rank P =0.10). In win ratio analysis, win ratio was 1.05 (95% CI, 0.97–1.13; P =0.20). Negative binomial regression and Andersen-Gill analyses which include repeated events showed statistically significant advantage for ticagrelor monotherapy (rate ratio, 0.92 [95% CI, 0.85–0.99; P =0.020] and hazard ratio, 0.92 [95% CI, 0.85–0.99; P =0.028], respectively), although in weighted composite end point analysis, the hazard ratio was 0.93 (95% CI, 0.84–1.04; log-rank P =0.22). Conclusions: Statistical analyses considering repeated events or event severity showed that ticagrelor monotherapy consistently reduced ischemic and bleeding events by 5% to 8%, compared with conventional 1-year DAPT. Applying multiple statistical methods could emphasize the multiple facets of a trial and result in accurate and more appropriate analyses. Considering the recurrence of ischemic and bleeding events, ticagrelor monotherapy appeared to be beneficial after percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435. Abstract : Supplemental Digital Content is available in the text.