Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE

A multicentre, randomised, double-blind trial

Faiez Zannad, Christopher P. Cannon, William Cushman, George L. Bakris, Venu Menon, Alfonso T. Perez, Penny R. Fleck, Cyrus R. Mehta, Stuart Kupfer, Craig Wilson, Hung Lam, William B. White

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2067-2076
Number of pages10
JournalThe Lancet
Volume385
Issue number9982
DOIs
StatePublished - May 23 2015
Externally publishedYes

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Type 2 Diabetes Mellitus
Heart Failure
Placebos
Mortality
Brain Natriuretic Peptide
Acute Coronary Syndrome
alogliptin
Unstable Angina
Cardiovascular Diseases
Stroke
Myocardial Infarction

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE : A multicentre, randomised, double-blind trial. / Zannad, Faiez; Cannon, Christopher P.; Cushman, William; Bakris, George L.; Menon, Venu; Perez, Alfonso T.; Fleck, Penny R.; Mehta, Cyrus R.; Kupfer, Stuart; Wilson, Craig; Lam, Hung; White, William B.

In: The Lancet, Vol. 385, No. 9982, 23.05.2015, p. 2067-2076.

Research output: Contribution to journalArticle

Zannad, F, Cannon, CP, Cushman, W, Bakris, GL, Menon, V, Perez, AT, Fleck, PR, Mehta, CR, Kupfer, S, Wilson, C, Lam, H & White, WB 2015, 'Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: A multicentre, randomised, double-blind trial', The Lancet, vol. 385, no. 9982, pp. 2067-2076. https://doi.org/10.1016/S0140-6736(14)62225-X
Zannad, Faiez ; Cannon, Christopher P. ; Cushman, William ; Bakris, George L. ; Menon, Venu ; Perez, Alfonso T. ; Fleck, Penny R. ; Mehta, Cyrus R. ; Kupfer, Stuart ; Wilson, Craig ; Lam, Hung ; White, William B. / Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE : A multicentre, randomised, double-blind trial. In: The Lancet. 2015 ; Vol. 385, No. 9982. pp. 2067-2076.
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T2 - A multicentre, randomised, double-blind trial

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AU - Cannon, Christopher P.

AU - Cushman, William

AU - Bakris, George L.

AU - Menon, Venu

AU - Perez, Alfonso T.

AU - Fleck, Penny R.

AU - Mehta, Cyrus R.

AU - Kupfer, Stuart

AU - Wilson, Craig

AU - Lam, Hung

AU - White, William B.

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N2 - 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.

AB - 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.

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