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Total cardiovascular events analysis of the EXAMINE trial in patients with type 2 diabetes and recent acute coronary syndrome.

ABSTRACT: Alogliptin, a dipeptidyl peptidase-4 inhibitor, is approved for the treatment of patients with type 2 diabetes (T2DM). EXAMINE was a randomized controlled clinical trial designed to demonstrate the cardiovascular (CV) safety of alogliptin. In the trial, 5380 patients with established T2DM who had a recent acute coronary syndrome event (between 15 and 90 days) were randomized to treatment with either alogliptin or placebo. To better understand and describe the CV safety of alogliptin, we analyzed data from the EXAMINE trial to determine whether treatment with alogliptin affected recurrent and total CV events. Poisson regression analysis compared the total number of occurrences of CV death, MI, stroke, unstable angina, and coronary revascularization between all patients randomized to alogliptin vs placebo groups. Patients with recurrent CV events were older and more likely to have renal disease and history of heart failure. There were 1100 first CV events and an additional 666 recurrent events over a median of 18 months of follow-up. There were no significant differences with regard to total number of events in patients treated with alogliptin (n = 873) or placebo (n = 893; P = 0.52). Furthermore, there were no differences in the types of events seen in patients treated with alogliptin or placebo. Alogliptin did not increase the risk of either first or recurrent CV events when compared with placebo in patients with T2DM and recent acute coronary syndrome. These data support the CV safety of alogliptin in patients who are at increased risk of future CV events.

SUBMITTER: Cavender MA

PROVIDER: S-EPMC6489788 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Total cardiovascular events analysis of the EXAMINE trial in patients with type 2 diabetes and recent acute coronary syndrome.

Cavender Matthew A MA White William B WB Liu Yuyin Y Massaro Joseph M JM Bergenstal Richard M RM Mehta Cyrus R CR Zannad Faiez F Heller Simon S Cushman William C WC Cannon Christopher P CP

Clinical cardiology 20180816 8

Alogliptin, a dipeptidyl peptidase-4 inhibitor, is approved for the treatment of patients with type 2 diabetes (T2DM). EXAMINE was a randomized controlled clinical trial designed to demonstrate the cardiovascular (CV) safety of alogliptin. In the trial, 5380 patients with established T2DM who had a recent acute coronary syndrome event (between 15 and 90 days) were randomized to treatment with either alogliptin or placebo. To better understand and describe the CV safety of alogliptin, we analyzed ...[more]

PMID: 29652078

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Project description:ImportanceBromodomain and extraterminal proteins are epigenetic regulators of gene transcription. Apabetalone is a selective bromodomain and extraterminal protein inhibitor targeting bromodomain 2 and is hypothesized to have potentially favorable effects on pathways related to atherothrombosis. Pooled phase 2 data suggest favorable effects on clinical outcomes.ObjectiveTo test whether apabetalone significantly reduces major adverse cardiovascular events.Design, setting, and participantsA randomized, double-blind, placebo-controlled trial, conducted at 190 sites in 13 countries. Patients with an acute coronary syndrome in the preceding 7 to 90 days, type 2 diabetes, and low high-density lipoprotein cholesterol levels were eligible for enrollment, which started November 11, 2015, and ended July 4, 2018, with end of follow-up on July 3, 2019.InterventionsPatients were randomized (1:1) to receive apabetalone, 100 mg orally twice daily (n = 1215), or matching placebo (n = 1210) in addition to standard care.Main outcomes and measuresThe primary outcome was a composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke.ResultsAmong 2425 patients who were randomized (mean age, 62 years; 618 women [25.6%]), 2320 (95.7%) had full ascertainment of the primary outcome. During a median follow-up of 26.5 months, 274 primary end points occurred: 125 (10.3%) in apabetalone-treated patients and 149 (12.4%) in placebo-treated patients (hazard ratio, 0.82 [95% CI, 0.65-1.04]; P = .11). More patients allocated to apabetalone than placebo discontinued study drug (114 [9.4%] vs 69 [5.7%]) for reasons including elevations of liver enzyme levels (35 [2.9%] vs 11 [0.9%]).Conclusions and relevanceAmong patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events.Trial registrationClinicalTrials.gov Identifier: NCT02586155.

Project description:Background Improved heart failure (HF) risk stratification after a recent acute coronary syndrome may identify those who can benefit from therapies that reduce HF risk. We aimed to identify clinical and biomarker predictors for expanded HF outcomes in patients with type 2 diabetes mellitus after recent acute coronary syndrome. Methods and Results The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial was a multicenter, non-inferiority, double-masked, placebo-controlled study which randomized 5380 patients with type 2 diabetes mellitus after recent acute coronary syndrome to alogliptin or placebo. Baseline biomarkers were measured in 5154 patients: NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin I, adiponectin, growth-differentiation-factor-15, and galectin-3. Our primary outcome was cardiovascular) death, HF hospitalization, elevated NT-proBNP during follow-up, or loop diuretics initiation. The association between clinical variables, biomarkers, and outcomes were assessed using Cox regression models. In the study population, the median age was 61.0 years, 67.7% were men, and 28.0% had baseline HF (median follow-up was 18 months). In multivariable analyses, NT-proBNP had the strongest association with the primary outcome (per log2, hazard ratio 1.24; Wald ?2 67.4; P<0.0001) followed by a prior HF history (hazard ratio 1.42; Wald ?2 20.8; P<0.0001). A model with clinical variables and biomarkers allowed for risk prediction for expanded HF outcomes (C-statistic=0.72). Discrimination results were similar for cardiovascular death or HF hospitalization. Conclusions Among patients with type 2 diabetes mellitus after recent acute coronary syndrome, the use biomarkers such as N-terminal pro-B-type natriuretic peptide and clinical variables enables risk stratification for expanded HF outcomes. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00968708.

Dataset Information

Total cardiovascular events analysis of the EXAMINE trial in patients with type 2 diabetes and recent acute coronary syndrome.

Publications

Total cardiovascular events analysis of the EXAMINE trial in patients with type 2 diabetes and recent acute coronary syndrome.

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