Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation: Per-Protocol Analysis of the GLOBAL LEADERS Trial.

Gragnano, Felice; Zwahlen, Marcel; Vranckx, Pascal; Heg, Dik; Schmidlin, Kurt; Hamm, Christian; Steg, Philippe Gabriel; Gargiulo, Giuseppe; McFadden, Eugene P; Onuma, Yoshinobu; Chichareon, Ply; Benit, Edouard; Möllmann, Helge; Janssens, Luc; Leonardi, Sergio; Zurakowski, Aleksander; Arrivi, Alessio; Van Geuns, Robert Jan; Huber, Kurt; Slagboom, Ton; ... (2022). Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation: Per-Protocol Analysis of the GLOBAL LEADERS Trial. Journal of the American Heart Association, 11(10), e024291. American Heart Association 10.1161/JAHA.121.024291

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Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P=0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Department of Clinical Research (DCR)
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

UniBE Contributor:

Zwahlen, Marcel, Heg, Dierik Hans, Schmidlin, Kurt, Windecker, Stephan

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2047-9980

Publisher:

American Heart Association

Language:

English

Submitter:

Pubmed Import

Date Deposited:

07 Mar 2022 11:43

Last Modified:

20 Feb 2024 14:16

Publisher DOI:

10.1161/JAHA.121.024291

PubMed ID:

35229616

Uncontrolled Keywords:

DAPT P2Y12 inhibitor monotherapy intention‐to‐treat per‐protocol ticagrelor

BORIS DOI:

10.48350/166332

URI:

https://boris.unibe.ch/id/eprint/166332

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