Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial.
By F. Zannad, C. Cannon, W. Cushman, G. Bakris, V. Menon, Alfonso T. Perez, P. Fleck, C. Mehta, S. Kupfer, C. Wilson and 2 more. The Lancet, 2015
676 citations recorded by the source corpus.
BACKGROUND The EXAMINE trial showed non-inferiority of the DPP-4 inhibitor alogliptin to placebo on major adverse cardiac event (MACE) rates in patients with type 2 diabetes and recent acute coronary syndromes. Concerns about excessive rates of in-hospital heart failure in another DPP-4 inhibitor trial have been reported. We therefore assessed hospital admission for heart failure in the EXAMINE trial. METHODS Patients with type 2 diabetes and an acute coronary syndrome event in the previous 15-90 days were randomly assigned alogliptin or placebo plus standard treatment for diabetes and cardiovascular disease prevention. The prespecified exploratory extended MACE endpoint was all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, urgent revascularisation due to unstable angina, and hospital admission for heart failure. The post-hoc analyses were of cardiovascular death and hospital admission for heart failure, assessed by history of heart failure and brain natriuretic peptide (BNP) concentration at baseline. We also assessed changes in N-terminal pro-BNP (NT-pro-BNP) from baseline to 6 months. This study is registered with ClinicalTrials.gov, number NCT00968708. FINDINGS 5380 patients were assigned to alogliptin (n=2701) or placebo (n=2679) and followed up for a median of 533 days (IQR 280-751). The exploratory extended MACE endpoint was seen in 433 (16·0%) patients assigned to alogliptin and in 441 (16·5%) assigned to placebo (hazard ratio [HR] 0·98, 95% CI 0·86-1·12). Hospital admission for heart failure was the first event in 85 (3·1%) patients taking alogliptin compared with 79 (2·9%) taking placebo (HR 1·07, 95% CI 0·79-1·46). Alogliptin had no effect on composite events of cardiovascular death and hospital admission for heart failure in the post hoc analysis (HR 1·00, 95% CI 0·82-1·21) and results did not differ by baseline BNP concentration. NT-pro-BNP concentrations decreased significantly and similarly in the two groups. INTERPRETATION In patients with type 2 diabetes and recent acute coronary syndromes, alogliptin did not increase the risk of heart failure outcomes. FUNDING Takeda Development Center Americas.
Subfields: Cardiology and Cardiovascular Medicine, Endocrinology, Diabetes and Metabolism
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In Endocrinology, Diabetes and Metabolism
Citations in the corpus
- Update on the treatment of type 2 diabetes mellitus. (2016, background): “In a post hoc analysis of the data, there was no significant difference in the rate of hospitalization for heart failure (3.1% and 2.9% in the branches of alogliptin and placebo, respectively; HR = 1.07, 95%CI: 0.79-1.46) [133 ] .”
- Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction (2016, neutral): “9) Left ventricular ejection fraction, % 25 (20-33) 25 (19-32) Left ventricular end-diastolic volume index, mL/m2 140 (112-173) 137 (115-174) Left ventricular end-systolic volume index, mL/m2 104 (78-130) 100 (80-133) Ratio of early mitral inflow velocity to early diastolic medial mitral annular vel”
- Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and Clinical Considerations (2016, neutral): “Hospitalization for heart failure was not increased in the alogliptin-treated group in those with history of heart failure or higher baseline B-type natriuretic peptide (BNP) concentration.(485) Increased risk of hospitalization for heart failure was not consistent across SAVOR-TIMI 53, EXAMINE, and”