William B White1, Stuart Kupfer2, Faiez Zannad3, Cyrus R Mehta4, Craig A Wilson2, Lanyu Lei5, George L Bakris6, Steven E Nissen7, William C Cushman8, Simon R Heller9, Richard M Bergenstal10, Penny R Fleck2, Christopher P Cannon11. 1. University of Connecticut School of Medicine, Farmington, CT wwhite@uchc.edu. 2. Takeda Development Center Americas, Inc., Deerfield, IL. 3. INSERM 9501, Universite de Lorraine and CHU, Nancy, France. 4. Harvard School of Public Health, Boston, MA. 5. Harvard Clinical Research Institute, Boston, MA. 6. The University of Chicago Medicine, Chicago, IL. 7. Cleveland Clinic Foundation, Cleveland, OH. 8. The University of Tennessee Health Science Center College of Medicine, Memphis VA Medical Center, Memphis, TN. 9. University of Sheffield, Sheffield, U.K. 10. International Diabetes Center, Park-Nicollet Clinic, Minneapolis, MN. 11. Harvard Clinical Research Institute, Boston, MA Harvard Medical School, Boston, MA.
Abstract
OBJECTIVE: We evaluated the risk of cardiovascular (CV) death in all Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study participants and in those who experienced an on-study, major nonfatal CV event. RESEARCH DESIGN AND METHODS: The study randomly assigned 5,380 patients with type 2 diabetes toalogliptin or placebowithin 15 to 90 days of an acute coronary syndrome (ACS). Deaths and nonfatal CV events (myocardial infarction [MI], stroke, hospitalized heart failure [HHF], and hospitalization for unstable angina [UA]) were adjudicated. Patients were monitored until censoring or death, regardless of a prior postrandomized nonfatal CV event. Time-updated multivariable Cox models were used to estimate the risk of death in the absence of or after each nonfatal event. RESULTS:Rates of CV death were 4.1% for alogliptin and 4.9% for placebo (hazard ratio [HR] 0.85; 95% CI 0.66, 1.10). A total of 736 patients (13.7%) experienced a first nonfatal CV event (5.9% MI, 1.1% stroke, 3.0% HHF, and 3.8% UA). Compared with patients not experiencing a nonfatal event, the adjusted HR (95% CI) for death was 3.12 after MI (2.13, 4.58; P < 0.0001) 4.96 after HHF (3.29, 7.47; P < 0.0001), 3.08 after stroke (1.29, 7.37; P = 0.011), and 1.66 after UA (0.81, 3.37; P = 0.164). Mortality rates after a nonfatal event were comparable for alogliptin and placebo. CONCLUSIONS: In patients with type 2 diabetes and a recent ACS, the risk of CV death was higher after a postrandomization, nonfatal CV event, particularly heart failure, compared with those who did not experience a CV event. The risk of CV death was similar between alogliptin and placebo.
RCT Entities:
OBJECTIVE: We evaluated the risk of cardiovascular (CV) death in all Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study participants and in those who experienced an on-study, major nonfatal CV event. RESEARCH DESIGN AND METHODS: The study randomly assigned 5,380 patients with type 2 diabetes to alogliptin or placebo within 15 to 90 days of an acute coronary syndrome (ACS). Deaths and nonfatal CV events (myocardial infarction [MI], stroke, hospitalized heart failure [HHF], and hospitalization for unstable angina [UA]) were adjudicated. Patients were monitored until censoring or death, regardless of a prior postrandomized nonfatal CV event. Time-updated multivariable Cox models were used to estimate the risk of death in the absence of or after each nonfatal event. RESULTS: Rates of CV death were 4.1% for alogliptin and 4.9% for placebo (hazard ratio [HR] 0.85; 95% CI 0.66, 1.10). A total of 736 patients (13.7%) experienced a first nonfatal CV event (5.9% MI, 1.1% stroke, 3.0% HHF, and 3.8% UA). Compared with patients not experiencing a nonfatal event, the adjusted HR (95% CI) for death was 3.12 after MI (2.13, 4.58; P < 0.0001) 4.96 after HHF (3.29, 7.47; P < 0.0001), 3.08 after stroke (1.29, 7.37; P = 0.011), and 1.66 after UA (0.81, 3.37; P = 0.164). Mortality rates after a nonfatal event were comparable for alogliptin and placebo. CONCLUSIONS: In patients with type 2 diabetes and a recent ACS, the risk of CV death was higher after a postrandomization, nonfatal CV event, particularly heart failure, compared with those who did not experience a CV event. The risk of CV death was similar between alogliptin and placebo.
Authors: Matthew A Cavender; William B White; Yuyin Liu; Joseph M Massaro; Richard M Bergenstal; Cyrus R Mehta; Faiez Zannad; Simon Heller; William C Cushman; Christopher P Cannon Journal: Clin Cardiol Date: 2018-08-16 Impact factor: 2.882
Authors: Scott A Hubers; Jessica R Wilson; Chang Yu; Hui Nian; Eric Grouzmann; Philippe Eugster; Cyndya A Shibao; Frederic T Billings; Scott Jafarian Kerman; Nancy J Brown Journal: Hypertension Date: 2018-09 Impact factor: 10.190
Authors: Matthew J O'Brien; Susan L Karam; Amisha Wallia; Raymond H Kang; Andrew J Cooper; Nicola Lancki; Margaret R Moran; David T Liss; Theodore A Prospect; Ronald T Ackermann Journal: JAMA Netw Open Date: 2018-12-07
Authors: Xavier Rossello; João Pedro Ferreira; Francisca Caimari; Zohra Lamiral; Abhinav Sharma; Cyrus Mehta; George Bakris; Christopher P Cannon; William B White; Faiez Zannad Journal: Clin Res Cardiol Date: 2021-04-30 Impact factor: 5.460