학술논문
Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial
Document Type
article
Author
Maggioni, AP; Greene, SJ; Fonarow, GC; Bohm, M; Zannad, F; Solomon, SD; Lewis, EF; Baschiera, F; Hua, TA; Gimpelewicz, CR; Lesogor, A; Gheorghiade, M; Ramos, S; Luna, A; Miriuka, S; Diez, M; Perna, E; Luquez, H; Pinna, JG; Castagnino, J; Alvarenga, P; Ibanez, J; Blumberg, ES; Dizeo, C; Guerrero, RA; Schygiel, P; Milesi, R; Sosa, C; Hominal, M; Marquez, LL; Poy, C; Hasbani, E; Vico, M; Fernandez, A; Vita, N; Vanhaecke, J; De Keulenaer, G; Striekwold, H; Vervoort, G; Vrolix, M; Henry, P; Dendale, P; Smolders, W; Marechal, P; Vandekerckhove, H; Oliveira, M; Neuenschwande, F; Reis, G; Saraiva, J; Bodanese, L; Canesin, M; Greco, O; Bassan, R; Marino, RL; Giannetti, N; Moe, G; Sussex, B; Sheppard, R; Huynh, T; Stewart, R; Haddad, H; Echeverria, L; Quintero, A; Torres, A; Jaramillo, M; Lopez, M; Mendoza, F; Florez, N; Cotes, C; Garcia, M; Belohlavek, J; Hradec, J; Peterka, M; Gregor, P; Monhart, Z; Jansky, P; Kettner, J; Reichert, P; Spinar, J; Brabec, T; Hutyra, M; Solar, M; Pietila, M; Nyman, K; Pajari, R; Cohen, A; Galinier, M; Gosse, P; Livarek, B; Neuder, Y; Jourdain, P; Picard, F; Isnard, R; Hoppe, U; Kaeaeb, S; Rosocha, S; Prondzinsky, R; Felix, S; Duengen, H-D; Figulla, H-R
Source
European Heart Journal. 34(40)
Subject
Language
Abstract
AimsThe 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 resultsASTRONAUT 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: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; 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: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; 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: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction).ConclusionThis 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.