EXAMINE Trial Post-Hoc Analysis: Prior CV Event Increased Mortality Risk in Type 2 Diabetes
Researchers evaluated the risk for cardiovascular death in all EXAMINE participants.
NEW ORLEANS — Risk for cardiovascular (CV) death appears to be increased in patients with type 2 diabetes and cardiovascular disease (CVD) who have experienced a CV event, especially for those who have been hospitalized for heart failure, a new analysis of the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin vs Standard Care) study suggests.1
The data from the post-hoc analysis were presented at the American Diabetes Association (ADA) 76th Scientific Sessions.
Results from EXAMINE, a CV outcomes trial, were initially published in the New England Journal of Medicine in 2013.2 The study included patients with type 2 diabetes who had sustained acute coronary syndrome (ACS) within 15 to 90 days of enrollment (n=5380). They were then randomly assigned to placebo (n=2679) or alogliptin 25 mg (Nesina, Takeda) once daily (n=2701). The primary end point was time to major adverse CV event (MACE), which included CV death, nonfatal myocardial infarction (MI), and nonfatal stroke. Median follow-up was about 18 months.
The researchers' objective in this post-hoc analysis was to evaluate the risk for CV death in all EXAMINE participants as well as in those who experienced a nonfatal CV event during the study. Deaths and major nonfatal CV events were adjudicated.
During the study, 13.7% of patients experienced a first nonfatal CV event, including MI (5.9%), stroke (1.1%), hospitalization for heart failure (3.0%), and unstable angina (3.8%).3
Compared with those who had not experienced a nonfatal CV event, risk for death increased significantly after MI (adjusted HR=3.12; 95% CI, 2.13-4.58), hospitalization for heart failure (adjusted HR=4.96; 95% CI, 3.29-7.47), stroke (adjusted HR=3.08; 95% CI, 1.29-7.37), and unstable angina (adjusted HR=1.66; 95% CI, 0.81-3.37).3
Additionally, mortality rates were 4.5% in the alogliptin group and 4.9% in the placebo group. The risk for CV death slightly favored alogliptin over placebo, but the difference was not statistically significant (HR=0.85; 95% CI, 0.66-1.10).1
For those who were hospitalized for heart failure, however, mortality rates were 22.7% in the alogliptin group vs 34.1% in the placebo group (HR=1.02; 95% CI, 0.51-2.02).1
“The startling thing in this study is the effect for those hospitalized for heart failure,” study researcher Simon Heller, MD, professor at the University of Sheffield in the United Kingdom, said during a press conference.
Dr Heller's comments were echoed by lead investigator William B. White, MD, professor of medicine, The Pat and Jim Calhoun Cardiology Center, UConn Health.
“Heart failure is a powerful predictor of mortality in patients with both type 2 diabetes and coronary heart disease,” he said in a press release. “This study suggests that we have an important opportunity to evaluate and understand the factors underlying incident heart failure in order to improve prevention strategies. These findings emphasize how critical it is to aggressively make use of evidence-based, secondary preventive therapies, which should be considered a standard in the clinical management of patients with type 2 diabetes who are at high risk for cardiovascular disease.”
Disclosures: Dr Heller has received research support from, is a consultant for, or serves on a speaker's bureau for Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Takeda Development Center Americas Inc, Sanofi-Aventis Deutschland GmBH, Merck & Co, and Medtronic. Dr White is an employee of or has an other relationship with Takeda Development Center Americas Inc,
- White WB, Kupfer S, Cannon CP, et al. Abstract 1090-P. Mortality Findings from the EXAMINE Trial. Presented at: ADA 76th Scientific Sessions; June 10-14, 2016; New Orleans, LA.
- White WB, Cannon CP, Heller SR, et al; for the EXAMINE Investigators. Alogliptin after Acute Coronary Syndrome in Patients With Type 2 Diabetes. N Engl J Med. 2013;369:1327-1335.
- White WB, Kupfer S, Zannad F, et al; for the EXAMINE Investigators. Cardiovascular Mortality in Patients With Type 2 Diabetes and Recent Acute Coronary Syndromes From the EXAMINE Trial. Diabetes Care. 2016;doi:10.2337/dc16-0303.