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Title
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Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial
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Author
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Institution/Organisation
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ASTRONAUT Investigators
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Abstract
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| AIM The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95 CI: 0.640.99; DM: HR: 1.16, 95 CI: 0.911.47; P 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95 CI: 0.500.94; DM: HR: 1.64, 95 CI: 1.152.33; P 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium 6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95 CI: 0.711.93; DM: HR: 2.39, 95 CI: 1.304.42; P 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM. |
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Language
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English
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Source (journal)
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European heart journal. - London
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Publication
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London
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2013
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ISSN
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0195-668X
[Print]
1522-9645
[Online]
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DOI
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10.1093/EURHEARTJ/EHT342
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Volume/pages
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34
:40
(2013)
, p. 3117-3127
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ISI
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000326292600011
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Full text (Publisher's DOI)
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