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Clinical Trial
. 2022 May 17;11(10):e024291.
doi: 10.1161/JAHA.121.024291. Epub 2022 Mar 1.

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

Felice Gragnano  1   2 , Marcel Zwahlen  3 , Pascal Vranckx  4   5 , Dik Heg  6 , Kurt Schmidlin  3 , Christian Hamm  7   8 , Philippe Gabriel Steg  9 , Giuseppe Gargiulo  10 , Eugene P McFadden  11   12 , Yoshinobu Onuma  13 , Ply Chichareon  14 , Edouard Benit  15 , Helge Möllmann  16 , Luc Janssens  17 , Sergio Leonardi  18 , Aleksander Zurakowski  19   20 , Alessio Arrivi  21 , Robert Jan Van Geuns  22 , Kurt Huber  23   24 , Ton Slagboom  25 , Paolo Calabrò  2 , Patrick W Serruys  26   27 , Peter Jüni  28 , Marco Valgimigli  29 , Stephan Windecker  1 ; GLOBAL LEADERS Investigators [Link]
Collaborators, Affiliations
Clinical Trial

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

Felice Gragnano et al. J Am Heart Assoc. .

Abstract

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.

Keywords: DAPT; P2Y12 inhibitor monotherapy; intention‐to‐treat; per‐protocol; ticagrelor.

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Figures

Figure 1
Figure 1. Distribution of protocol deviators and nondeviators in GLOBAL LEADERS at 2 years.
A, Design of the GLOBAL LEADERS trial. B, Time trend of protocol deviators (bar graphs), nondeviators (lines), and deaths (bar graphs) at 2 years stratified by treatment strategy. ACS indicates acute coronary syndrome; CCS, chronic coronary syndrome; DAPT, dual antiplatelet therapy; and R, randomization.
Figure 2
Figure 2. Per‐protocol and intention‐to‐treat effect of ticagrelor monotherapy from 1 month vs standard antiplatelet regimens after coronary stent implantation.
Among patients who complied with the study protocol in the GLOBAL LEADERS, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard DAPT followed by aspirin alone 2 years after coronary stenting. The per‐protocol and intention‐to‐treat effect estimates were overall consistent. ACS indicates acute coronary syndrome; ASA, acetylsalicylic acid; bid, bis in die (twice daily); CCS, chronic coronary syndrome; and DAPT, dual antiplatelet therapy.
Figure 3
Figure 3. Cumulative incidence of all‐cause mortality at 2 years in the per‐protocol population.
RR indicates rate ratio.
See this image and copyright information in PMC

Comment in

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