Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial

Rafael Romaguera, Pablo Salinas, Josep Gomez-Lara, Salvatore Brugaletta, Antonio Gómez-Menchero, Miguel A Romero, Sergio García-Blas, Raymundo Ocaranza, Pascual Bordes, Marcelo Jiménez Kockar, Neus Salvatella, Victor A Jiménez-Díaz, Mar Alameda, Ramiro Trillo, Dae Hyun Lee, Pedro Martín, María López-Benito, Alfonso Freites, Virginia Pascual-Tejerina, Felipe Hernández-Hernández, Bruno García Del Blanco, Mohsen Mohandes, Francisco Bosa, Eduardo Pinar, Gerard Roura, Josep Comin-Colet, Antonio Fernández-Ortiz, Carlos Macaya, Xavier Rossello, Manel Sabate, Stuart J Pocock, Joan A Gómez-Hospital, SUGAR trial investigators, Carlos H Salazar, Luis Ortega-Paz, José M de la Torre Hernández, Armando Pérez de Prado, Juan Sanchis, Soledad Ojeda, José L Ferreiro, Montserrat Gracida, Lara Fuentes, Luis Teruel, Guillem Muntané-Carol, Rocío Castillo-Poyo, Pilar Jiménez-Quevedo, Angel Cequier, Rafael Romaguera, Pablo Salinas, Josep Gomez-Lara, Salvatore Brugaletta, Antonio Gómez-Menchero, Miguel A Romero, Sergio García-Blas, Raymundo Ocaranza, Pascual Bordes, Marcelo Jiménez Kockar, Neus Salvatella, Victor A Jiménez-Díaz, Mar Alameda, Ramiro Trillo, Dae Hyun Lee, Pedro Martín, María López-Benito, Alfonso Freites, Virginia Pascual-Tejerina, Felipe Hernández-Hernández, Bruno García Del Blanco, Mohsen Mohandes, Francisco Bosa, Eduardo Pinar, Gerard Roura, Josep Comin-Colet, Antonio Fernández-Ortiz, Carlos Macaya, Xavier Rossello, Manel Sabate, Stuart J Pocock, Joan A Gómez-Hospital, SUGAR trial investigators, Carlos H Salazar, Luis Ortega-Paz, José M de la Torre Hernández, Armando Pérez de Prado, Juan Sanchis, Soledad Ojeda, José L Ferreiro, Montserrat Gracida, Lara Fuentes, Luis Teruel, Guillem Muntané-Carol, Rocío Castillo-Poyo, Pilar Jiménez-Quevedo, Angel Cequier

Abstract

Aim: Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes.

Methods and results: We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44-0.96; Pnon-inferiority < 0.001; Psuperiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46-0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups.

Conclusion: In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome.

Clinical trial registration: ClinicalTrials.gov: NCT03321032.

Keywords: Diabetes mellitus; Drug-eluting stents; Percutaneous coronary intervention; Randomized trial.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Graphical Abstract
Graphical Abstract
In the SUGAR trial, 1175 patients with diabetes mellitus and coronary artery disease were randomly assigned to receive Cre8 EVO or Resolute Onyx stents. Patients allocated to Cre8 EVO stents had a reduced risk of target lesion failure at 1-year follow-up.
Figure 1
Figure 1
Trial flowchart.
Figure 2
Figure 2
Primary endpoint and its components. Time-to-event curves are shown for patients in the intention-to-treat population who were randomly assigned to receive Cre8 EVO stents or Resolute Onyx stents. CI, confidence interval; HR, hazard ratio; MI, myocardial infarction.
Figure 3
Figure 3
Prespecified subgroup analyses of the primary endpoint. AMI, acute myocardial infarction; HbA1c, glycated haemoglobin; LDL, low-density lipoprotein cholesterol; SGLT2i, sodium-glucose cotransporter 2 inhibitors; STEMI, ST-elevation myocardial infarction.

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Source: PubMed

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