Ticagrelor monotherapy in patients with concomitant diabetes mellitus and chronic kidney disease: a post hoc analysis of the GLOBAL LEADERS trial

Cardiovascular Diabetology

Hideyuki Kawashima¹  Kuniaki Takahashi¹  Masafumi Ono¹  Hironori Hara¹  Pascal Vranckx²  Marco Valgimigli³  Stephan Windecker³  Patrick W. Serruys⁴  Yoshinobu Onuma⁴  Robert-Jan van Geuns⁵  Michael Haude⁶  Scot Garg⁷  Rutao Wang⁸  Chao Gao⁸  Dominick J. Angiolillo⁹  Philippe Gabriel Steg^1,10  Mariusz Tomaniak^1,11  Christian Hamm^1,12  Ton Slagboom^1,13  Gilles Montalescot^1,14 

[1] Amsterdam UMC, University of Amsterdam;Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Jessa Ziekenhuis;Department of Cardiology, Bern University Hospital;Department of Cardiology, National University of Ireland Galway;Department of Cardiology, Radboud University;Department of Cardiology, Rheinland Klinikum Neuss, Lukaskrankenhaus;Department of Cardiology, Royal Blackburn Hospital;Department of Cardiology, Xijing hospital;Division of Cardiology, University of Florida College of Medicine;FACT, French Alliance for Cardiovascular Trials;First Department of Cardiology, Medical University of Warsaw;Kerckhoff Heart Center;OLVG;Sorbonne University, ACTION Study Group, Institute of Cardiology, Pitié-Salpêtrière Hospital;

关键词: Chronic kidney disease;    Diabetes mellitus;    Percutaneous coronary intervention;    DAPT;    Ticagrelor;    Aspirin-free antiplatelet strategies;   

DOI  :  10.1186/s12933-020-01153-x

来源: DOAJ

【 摘 要 】

Abstract Background Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients. Methods In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events. Results At 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66–2.80], p < 0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM + /CKD + patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55–0.99], p = 0.043, pinteraction = 0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56–0.99], p = 0.044, pinteraction = 0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95% CI [0.29–0.82], p = 0.007, pinteraction = 0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29–0.82], p = 0.007, pinteraction = 0.013) in the second year. Conclusion Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating. Clinical Trial Registration: ClinicalTrials.gov (NCT01813435).

【 授权许可】

Unknown