Takeda to present results from global EXAMINE CV safety outcomes trial at ACC 2014

Mar 28 2014

Sub-analyses Investigate the Effects of Vipidia® (alogliptin) on Cardiovascular Mortality Rates and Hospitalization for Heart Failure in Type 2 Diabetes Patients with Recent Acute Coronary Syndrome

Takeda Pharmaceuticals Company Limited (Takeda) will present sub-analyses from the global EXAMINE (EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) cardiovascular (CV) safety outcomes trial in a poster session at the American College of Cardiology’s (ACC) 63rd Annual Scientific Session in Washington, DC. These sub-analyses specifically investigated the effects of the dipeptidyl peptidase-4 inhibitor (DPP-4i) alogliptin on rates of CV mortality and hospitalization for heart failure (HF).

Alogliptin is the first and only DPP-4i to demonstrate CV safety outcomes in Type 2 diabetes patients with recent acute coronary syndrome (ACS). Heart disease, or cardiovascular disease (CVD), is the leading cause of morbidity and mortality in patients with Type 2 diabetes, and is responsible for between 50 and 80 percent of deaths in people with diabetes.

Findings from the sub-analysis, “Cardiovascular mortality in patients with type 2 diabetes and recent acute coronary syndrome from the EXAMINE Trial,” demonstrated no effect on rates of CV mortality [hazard ratio (HR)= 0.85, 95% confidence interval (CI): 0.66, 1.10] in patients with Type 2 diabetes and recent ACS with alogliptin, compared to placebo (n=112, 4.1% and n=130, 4.9%, respectively). There was also no increase in sudden cardiac death with alogliptin (n=59, 2.2%) versus placebo (n=73, 2.7%) [HR=0.80, 95% CI: 0.57, 1.12].

The other sub-analysis, “Alogliptin in patients with type 2 diabetes after acute coronary syndromes: Heart failure outcomes and cardiovascular safety in heart failure patients,” demonstrated that in patients with Type 2 diabetes and recent ACS, the pre-specified composite CV outcome of first occurrence of all-cause mortality, nonfatal MI and stroke, urgent revascularization due to unstable angina, and hospitalization for HF was similar for alogliptin compared with placebo [HR=0.98, 95% CI, 0.86-1.12]. Within this composite endpoint, hospitalized HF occurred in 3.1 percent of patients on alogliptin versus 2.9 percent on placebo [HR=1.07, 95% CI, 0.79-1.46]. Additionally, alogliptin neither induced new onset HF nor worsened HF outcomes in patients with a history of HF and / or with markers for HF (elevated NT-pro-BNP levels).

“Cardiovascular events are by far the commonest cause of death in patients with Type 2 diabetes.It is important, therefore that anti-diabetes therapies are not only efficacious in improving glycaemic control but also do not increase cardiovascular risk, ” said Prof. Anthony H. Barnett BSC (Hons) MD FRCP from the University of Birmingham and the Heart of England NHS Foundation Trust, Birmingham, UK. “Based on the data from the EXAMINE trial presented, alogliptin showed no difference from placebo when added to standard of care on rates of cardiovascular mortality and cardiovascular events. There was also no increase in hospitalized heart failure in this high risk population. This agent offers the NHS good value and should make an important addition to our therapeutic armamentarium.” 

Results from EXAMINE, a global, large, randomized, double-blind, placebo-controlled clinical trial, were published in the New England Journal of Medicine in September 2013. The trial was designed to evaluate CV safety following treatment with alogliptin in addition to standard of care, versus placebo in addition to standard of care, in patients with Type 2 diabetes and a recent ACS.5 The EXAMINE trial’s primary composite endpoint of non-inferiority compared to placebo in addition to standard of care was met, showing no increase in CV risk in a Type 2 diabetes patient population at high risk for CV events, including CV death, nonfatal myocardial infarction and nonfatal stroke.

“Takeda is committed to working with key investigators to continue analyzing and publishing relevant findings from the EXAMINE trial,” said Ajay Ahuja, MD, vice president, Medical Affairs, Takeda. “Findings from such sub-analyses provide further important information about alogliptin for this patient population.”