1. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial
- 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, and Figulla, H-R
- Subjects
Heart Disease ,Clinical Research ,Clinical Trials and Supportive Activities ,Diabetes ,Cardiovascular ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Metabolic and endocrine ,Administration ,Oral ,Amides ,Cardiotonic Agents ,Death ,Sudden ,Cardiac ,Diabetic Cardiomyopathies ,Double-Blind Method ,Female ,Fumarates ,Heart Failure ,Hospitalization ,Humans ,Kaplan-Meier Estimate ,Male ,Middle Aged ,Prospective Studies ,Renin ,Treatment Outcome ,Aliskiren ,Outcomes ,Post-discharge ,ASTRONAUT Investigators and Coordinators ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology - 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.
- Published
- 2013