Cargando…

Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial

BACKGROUND: In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once‐weekly resulted in a nonsignificant reduction in major adverse cardiovascular events (MACEs) and a nominal 14% reduction in all‐cause mortality in 14 752 patients with type 2 diabetes mellitus (T2DM) with an...

Descripción completa

Detalles Bibliográficos
Autores principales: Mentz, Robert J., Bethel, M. Angelyn, Merrill, Peter, Lokhnygina, Yuliya, Buse, John B., Chan, Juliana C., Felício, João S., Goodman, Shaun G., Choi, Jasmine, Gustavson, Stephanie M., Iqbal, Nayyar, Lopes, Renato D., Maggioni, Aldo P., Öhman, Peter, Pagidipati, Neha J., Poulter, Neil R., Ramachandran, Ambady, Reicher, Barry, Holman, Rury R., Hernandez, Adrian F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404902/
https://www.ncbi.nlm.nih.gov/pubmed/30371301
http://dx.doi.org/10.1161/JAHA.118.009304
_version_ 1783400977104109568
author Mentz, Robert J.
Bethel, M. Angelyn
Merrill, Peter
Lokhnygina, Yuliya
Buse, John B.
Chan, Juliana C.
Felício, João S.
Goodman, Shaun G.
Choi, Jasmine
Gustavson, Stephanie M.
Iqbal, Nayyar
Lopes, Renato D.
Maggioni, Aldo P.
Öhman, Peter
Pagidipati, Neha J.
Poulter, Neil R.
Ramachandran, Ambady
Reicher, Barry
Holman, Rury R.
Hernandez, Adrian F.
author_facet Mentz, Robert J.
Bethel, M. Angelyn
Merrill, Peter
Lokhnygina, Yuliya
Buse, John B.
Chan, Juliana C.
Felício, João S.
Goodman, Shaun G.
Choi, Jasmine
Gustavson, Stephanie M.
Iqbal, Nayyar
Lopes, Renato D.
Maggioni, Aldo P.
Öhman, Peter
Pagidipati, Neha J.
Poulter, Neil R.
Ramachandran, Ambady
Reicher, Barry
Holman, Rury R.
Hernandez, Adrian F.
author_sort Mentz, Robert J.
collection PubMed
description BACKGROUND: In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once‐weekly resulted in a nonsignificant reduction in major adverse cardiovascular events (MACEs) and a nominal 14% reduction in all‐cause mortality in 14 752 patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease. Whether patients at increased risk for events experienced a comparatively greater treatment benefit with exenatide is unknown. METHODS AND RESULTS: In the EXSCEL population, we created risk scores for MACEs and all‐cause mortality using step‐wise selection of baseline characteristics. A risk score was calculated for each patient, and a time‐to‐event model for each end point was developed including the risk score, treatment assignment, and risk‐treatment interaction. Interaction P values evaluating for a differential treatment effect by baseline risk were reported. Over a median follow‐up of 3.2 years (interquartile range, 2.2, 4.4), 1091 (7.4%) patients died and 1744 (11.8%) experienced a MACE. Independent predictors of MACEs and all‐cause mortality included age, sex, comorbidities (eg, previous cardiovascular event), body mass index, blood pressure, hemoglobin A1c, and estimated glomerular filtration rate. The all‐cause mortality and MACE risk models had modest discrimination with optimism‐corrected c‐indices of 0.73 and 0.71, respectively. No interaction was observed between treatment effect and risk profile for either end point (both interactions, P>0.1). CONCLUSIONS: Baseline characteristics (eg, age, previous cardiovascular events) and routine laboratory values (eg, hemoglobin A1c, estimated glomerular filtration rate) provided modest prognostic value for mortality and MACEs in a broad population of patients with type 2 diabetes mellitus. Exenatide's effects on mortality and MACEs were consistent across the spectrum of baseline risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01144338.
format Online
Article
Text
id pubmed-6404902
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-64049022019-03-19 Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial Mentz, Robert J. Bethel, M. Angelyn Merrill, Peter Lokhnygina, Yuliya Buse, John B. Chan, Juliana C. Felício, João S. Goodman, Shaun G. Choi, Jasmine Gustavson, Stephanie M. Iqbal, Nayyar Lopes, Renato D. Maggioni, Aldo P. Öhman, Peter Pagidipati, Neha J. Poulter, Neil R. Ramachandran, Ambady Reicher, Barry Holman, Rury R. Hernandez, Adrian F. J Am Heart Assoc Original Research BACKGROUND: In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once‐weekly resulted in a nonsignificant reduction in major adverse cardiovascular events (MACEs) and a nominal 14% reduction in all‐cause mortality in 14 752 patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease. Whether patients at increased risk for events experienced a comparatively greater treatment benefit with exenatide is unknown. METHODS AND RESULTS: In the EXSCEL population, we created risk scores for MACEs and all‐cause mortality using step‐wise selection of baseline characteristics. A risk score was calculated for each patient, and a time‐to‐event model for each end point was developed including the risk score, treatment assignment, and risk‐treatment interaction. Interaction P values evaluating for a differential treatment effect by baseline risk were reported. Over a median follow‐up of 3.2 years (interquartile range, 2.2, 4.4), 1091 (7.4%) patients died and 1744 (11.8%) experienced a MACE. Independent predictors of MACEs and all‐cause mortality included age, sex, comorbidities (eg, previous cardiovascular event), body mass index, blood pressure, hemoglobin A1c, and estimated glomerular filtration rate. The all‐cause mortality and MACE risk models had modest discrimination with optimism‐corrected c‐indices of 0.73 and 0.71, respectively. No interaction was observed between treatment effect and risk profile for either end point (both interactions, P>0.1). CONCLUSIONS: Baseline characteristics (eg, age, previous cardiovascular events) and routine laboratory values (eg, hemoglobin A1c, estimated glomerular filtration rate) provided modest prognostic value for mortality and MACEs in a broad population of patients with type 2 diabetes mellitus. Exenatide's effects on mortality and MACEs were consistent across the spectrum of baseline risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01144338. John Wiley and Sons Inc. 2018-09-20 /pmc/articles/PMC6404902/ /pubmed/30371301 http://dx.doi.org/10.1161/JAHA.118.009304 Text en © 2018 The Authors and AstraZeneca. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Mentz, Robert J.
Bethel, M. Angelyn
Merrill, Peter
Lokhnygina, Yuliya
Buse, John B.
Chan, Juliana C.
Felício, João S.
Goodman, Shaun G.
Choi, Jasmine
Gustavson, Stephanie M.
Iqbal, Nayyar
Lopes, Renato D.
Maggioni, Aldo P.
Öhman, Peter
Pagidipati, Neha J.
Poulter, Neil R.
Ramachandran, Ambady
Reicher, Barry
Holman, Rury R.
Hernandez, Adrian F.
Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial
title Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial
title_full Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial
title_fullStr Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial
title_full_unstemmed Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial
title_short Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial
title_sort effect of once‐weekly exenatide on clinical outcomes according to baseline risk in patients with type 2 diabetes mellitus: insights from the exscel trial
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404902/
https://www.ncbi.nlm.nih.gov/pubmed/30371301
http://dx.doi.org/10.1161/JAHA.118.009304
work_keys_str_mv AT mentzrobertj effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT bethelmangelyn effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT merrillpeter effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT lokhnyginayuliya effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT busejohnb effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT chanjulianac effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT feliciojoaos effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT goodmanshaung effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT choijasmine effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT gustavsonstephaniem effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT iqbalnayyar effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT lopesrenatod effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT maggionialdop effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT ohmanpeter effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT pagidipatinehaj effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT poulterneilr effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT ramachandranambady effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT reicherbarry effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT holmanruryr effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT hernandezadrianf effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial
AT effectofonceweeklyexenatideonclinicaloutcomesaccordingtobaselineriskinpatientswithtype2diabetesmellitusinsightsfromtheexsceltrial