TY - JOUR
T1 - Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups Results From the Randomized CREDENCE Trial
AU - Mahaffey, Kenneth W.
AU - Jardine, Meg J.
AU - Bompoint, Severine
AU - Cannon, Christopher P.
AU - Neal, Bruce
AU - Heerspink, Hiddo J. L.
AU - Charytan, David M.
AU - Edwards, Robert
AU - Agarwal, Rajiv
AU - Bakris, George
AU - Bull, Scott
AU - Capuano, George
AU - de Zeeuw, Dick
AU - Greene, Tom
AU - Levin, Adeera
AU - Pollock, Carol
AU - Sun, Tao
AU - Wheeler, David C.
AU - Yavin, Yshai
AU - Zhang, Hong
AU - Zinman, Bernard
AU - Rosenthal, Norman
AU - Brenner, Barry M.
AU - Perkovic, Vlado
AU - Ahuad Guerrero, Rodolfo Andres
AU - Aizenberg, Diego
AU - Pablo Albisu, Juan
AU - Alvarisqueta, Andres
AU - Bartolacci, Ines
AU - Alberto Berli, Mario
AU - Bordonava, Anselmo
AU - Calella, Pedro
AU - Cecilia Cantero, Maria
AU - Rodolfo Cartasegna, Luis
AU - Cercos, Esteban
AU - Cecilia Coloma, Gabriela
AU - Colombo, Hugo
AU - Commendatore, Victor
AU - Cuadrado, Jesus
AU - Alberto Cuneo, Carlos
AU - Maria Cusumano, Ana
AU - Guillermo Douthat, Walter
AU - Dario Dran, Ricardo
AU - Farias, Eduardo
AU - Florencia Fernandez, Maria
AU - Finkelstein, Hernan
AU - Fragale, Guillermo
AU - Osvaldo Fretes, Jose
AU - Horacio Garcia, Nestor
AU - Philip, Sam
AU - CREDENCE Study Investigators
N1 - Sources of Funding
This study is sponsored by Janssen Research & Development, LLC, which funded the trial. The sponsor was involved in the study design, the writing of the report, and the decision to submit the article for publication. Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation.
Acknowledgments
The authors thank all participants, investigators, and trial teams for their participation in the trial and the following people for their contributions to the statistical monitoring and analyses and the protocol development, safety monitoring, and operational implementation over the duration of the trial: Maria Ali, Jim Baldassarre, Dainius Balis, William Canovatchel, Jun Chen, Pei-Ling Chu, Trokon Cooke, Jag Craig, Jacki Danyluk, Mehul Desai, Lyndal Hones, Alan Jenkins, Mary Kavalam, Cha-Chi Lo, Xinchao Luo, Gary Meininger, Rich Oh, Rose Qiu, Nicole Schmitt, Danielle Siebenkaess, Roger Simpson, Anna Temu, Payal Thakkar, Michele Wells, and Renata Yong. The Steering Committee designed the study in conjunction with the sponsor. Dr Mahaffey wrote the first draft of the paper, had full access to the study design information, and had final responsibility for the decision to submit for publication. All authors provided input into subsequent drafts and approved the final version for submission. Editorial assistance for manuscript preparation was provided by Alaina Mitsch, PhD, and Kimberly Dittmar, PhD, of MedErgy, and was funded by Janssen Global Services, LLC. All authors reviewed and approved the manuscript.
PY - 2019/8/27
Y1 - 2019/8/27
N2 - Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease.
AB - Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease.
KW - canagliflozin
KW - clinical trial
KW - diabetes mellitus
KW - primary prevention
KW - renal insufficiency
KW - chronic
KW - secondary prevention
KW - EMPAGLIFLOZIN
KW - RATIONALE
KW - EVENTS
KW - DESIGN
KW - RISK
U2 - 10.1161/CIRCULATIONAHA.119.042007
DO - 10.1161/CIRCULATIONAHA.119.042007
M3 - Article
VL - 140
SP - 739
EP - 750
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 9
ER -
