A review of the latest clinical trial data from the American Diabetes Association's 76th Scientific Sessions in New Orleans, USA.
People with type 2 diabetes and heart disease who experience non-fatal cardiovascular events are at increased risk of cardiovascular-related death, and those previously hospitalised for heart failure are at highest risk, according to new analysis of data from the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial. The study is published online in Diabetes Care and was presented at the ADA conference.
Initial results from the EXAMINE trial, one of the first major cardiovascular outcomes studies of people with type 2 diabetes and coronary heart disease, were previously reported in 2013. The initial findings demonstrated that the DPP-4 inhibitor alogliptin did not increase risk of death or non-fatal cardiovascular events, such as stroke, myocardial infarction, hospitalisation for heart failure (HHF) or unstable angina (UA), compared to placebo.
In this new analysis, the same group of researchers evaluated the subsequent risk of cardiovascular mortality for EXAMINE’s 5,380 patients with type 2 diabetes, randomised to alogliptin (n=2,701) or placebo (n=2,679), beginning 15 to 90 days following an acute coronary syndrome—a broad term for any condition in which the heart's blood supply is blocked. Patients received standard care for both type 2 diabetes and cardiovascular risk factors throughout the study and were seen at outpatient visits every three months during the first year and every four months for the remainder of their participation in the trial—a median duration of 18 months.
During the course of the trial, 736 patients (13.7%) experienced at least one non-fatal cardiovascular event, including heart attacks (5.9%, n=316), stroke (1.1%, n=57), hospitalisation for heart failure (HHF) (3.0%, n=159) and unstable angina (UA) (3.8%, n=204). In total, 326 patients died during EXAMINE. The majority of deaths (n= 233) in the EXAMINE trial were among patients who did not experience a non-fatal cardiovascular event. However, those patients who did experience non-fatal cardiovascular events were at increased risk of cardiovascular-related death compared to those who did not experience nonfatal cardiovascular events. Cardiovascular-related deaths were defined as deaths from cardiac and cerebrovascular causes, as well as any other death without a known cause.
Patients with type 2 diabetes admitted to the hospital for heart failure during the trial (n=159) were at the highest increased risk for death due to cardiovascular causes. The data indicates their cardiovascular morbidity was more than four times higher: 20.1% (n=32) died of cardiovascularrelated causes, compared to 3.7% of the total 4,644 patients (n=172) who did not experience a non-fatal cardiovascular event during the trial.
The subsequent mortality rates for those who experienced a non-fatal stroke (8.8% of 57 patients, n= 5) or non-fatal heart attack (8.2% of 316, n= 26) during follow-up were twice as high compared to those who did not experience a non-fatal cardiovascular event. Of the 204 patients who were admitted to the hospital for unstable angina (UA), 3.4% (n=7) subsequently died from cardiovascular related causes.
Patients treated with the DPP-4 inhibitor alogliptin experienced no significant difference in mortality rates (4.1%), compared to those treated with placebo (4.9%, HR = 0.85, 95% CI, 0.66-1.10).