Ticagrelor alone versus dual antiplatelet therapy from 1 month after drug-eluting coronary stenting
Selected in Journal of the American College of Cardiology by S. Brugaletta
One of the most discussed limitations of GLOBAL-LEADER is the lack of event adjudication so that the rate of MI, bleeding or stent thrombosis between the two groups were unknown. In this study, events were adjudicated in those patients from the 20 top-enrolling participating sites.
References
Authors
Franzone A, McFadden E, Leonardi S, Piccolo R, Vranckx P, Serruys PW, Benit E, Liebetrau C, Janssens L, Ferrario M, Zurakowski A, Diletti R, Dominici M, Huber K, Slagboom T, Buszman P, Bolognese L, Tumscitz C, Bryniarski K, Aminian A, Vrolix M, Petrov I, Garg S, Naber C, Prokopczuk J, Hamm C, Steg PG, Heg D, Jüni P, Windecker S, Valgimigli M and for the GLASSY Investigators
Reference
J Am Coll Cardiol. 2019 Sept;74(18):2223–34
Published
November 2019
Link
Read the abstractReviewer
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Why this study – the rationale/objective?
The GLOBAL LEADERS (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Antiplatelet Therapy After Stent Implantation) study randomly assigned 15,991 patients undergoing percutaneous coronary intervention to 1-month dual antiplatelet therapy (DAPT) followed by 23-month ticagrelor monotherapy or conventional 12-month DAPT followed by 12-month aspirin. Apart from Q-wave myocardial infarction (MI), all study endpoints were analyzed as investigator reported.
The present analysis was a pre-specified ancillary study assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment for the coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke, or urgent target vessel revascularization and superior in preventing BARC 3 (Bleeding Academic Research Consortium) or 5 bleeding (coprimary safety endpoint) at 2 years with a 0.025 significance level to preserve nominal 5% alpha error.
How was it executed – the methodology?
An independent clinical event committee adjudicated investigator-reported and eventually unreported events of 7,585 patients from the 20 top-enrolling participating sites.
What is the main result?
The 2-year coprimary efficacy endpoint occurred in 271 (7.14%) and in 319 (8.41%) patients in the experimental and conventional groups, respectively (rate ratio [RR]: 0.85; 95% confidence interval [CI]: 0.72 to 0.99), fulfilling noninferiority (p noninferiority <0.001), but not superiority (p superiority =0.0465). The rates of BARC 3 or 5 bleeding did not differ (RR: 1.00; 95% CI: 0.75 to 1.33; p = 0.986). A time-dependent treatment effect was observed with the experimental strategy being associated with a lower risk of MI (RR: 0.54; 95% CI: 0.33 to 0.88; p interaction = 0.062) and definite stent thrombosis (RR: 0.14; 95% CI: 0.03 to 0.63; p interaction = 0.007) after 1-year post-percutaneous coronary intervention.
Critical reading and relevance for clinical practice
One of the most discussed limitations of the GLOBAL-LEADER is the lack of event adjudication so that it was unknown the rate of MI, bleeding or stent thrombosis between the two groups and if there was an advantage of the experimental arm over the control arm in terms of these endpoints. In this study, events were adjudicated in those patients from the 20 top-enrolling participating sites. Interestingly the study was powered for either the efficacy or the safety endpoints.
Overall, ticagrelor monotherapy after 1-month DAPT was noninferior, but not superior, to conventional treatment in the prevention of ischemic events, and it did not decrease major bleeding risk as compared with conventional treatment. One of the most interesting findings is that benefit of ticagrelor monotherapy seems to be higher after 1-year, when the control arm takes aspirin alone.
Multiple studies have shown that DAPT beyond 1 year reduces the risks of MI and ST compared with aspirin alone, but no study so far had observed this treatment benefit for ticagrelor alone versus aspirin.
Future studies should address then the pathophysiological mechanisms responsible for better late outcomes in patients who stop aspirin and continue ticagrelor monotherapy 1 month after PCI with drug-eluting coronary stents.
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