Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)

Nicolas F. Schroten; Kevin Damman; Marc H. Hemmelder; Adriaan A. Voors; Gerjan Navis; Carlo A. J. M. Gaillard; Dirk J. van Veldhuisen; Wiek H. van Gilst; Hans L. Hillege

doi:10.1016/j.ahj.2014.12.016

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)

Nicolas F. Schroten, Kevin Damman, Marc H. Hemmelder, Adriaan A. Voors, Gerjan Navis, Carlo A. J. M. Gaillard, Dirk J. van Veldhuisen, Wiek H. van Gilst, Hans L. Hillege^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

16 Citations (Scopus)

Abstract

AIMS: We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals.

METHODS AND RESULTS: Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007).

CONCLUSIONS: Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction.

Original language	English
Pages (from-to)	693-701
Number of pages	12
Journal	American Heart Journal
Volume	169
Issue number	5
DOIs	https://doi.org/10.1016/j.ahj.2014.12.016
Publication status	Published - May-2015

Keywords

CONVERTING-ENZYME-INHIBITION
CARDIORENAL END-POINTS
PROGNOSTIC VALUE
MYOCARDIAL-INFARCTION
RANDOMIZED-TRIAL
KIDNEY-FUNCTION
BASE-LINE
VAL-HEFT
MORTALITY
METAANALYSIS

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Schroten, N. F., Damman, K., Hemmelder, M. H., Voors, A. A., Navis, G., Gaillard, C. A. J. M., van Veldhuisen, D. J., van Gilst, W. H., & Hillege, H. L. (2015). Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction). American Heart Journal, 169(5), 693-701. https://doi.org/10.1016/j.ahj.2014.12.016

Schroten, Nicolas F. ; Damman, Kevin ; Hemmelder, Marc H. et al. / Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction). In: American Heart Journal. 2015 ; Vol. 169, No. 5. pp. 693-701.

@article{17cdae6fcec24f97a58b537ee16349be,

title = "Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)",

abstract = "AIMS: We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals.METHODS AND RESULTS: Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007).CONCLUSIONS: Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction.",

keywords = "CONVERTING-ENZYME-INHIBITION, CARDIORENAL END-POINTS, PROGNOSTIC VALUE, MYOCARDIAL-INFARCTION, RANDOMIZED-TRIAL, KIDNEY-FUNCTION, BASE-LINE, VAL-HEFT, MORTALITY, METAANALYSIS",

author = "Schroten, {Nicolas F.} and Kevin Damman and Hemmelder, {Marc H.} and Voors, {Adriaan A.} and Gerjan Navis and Gaillard, {Carlo A. J. M.} and {van Veldhuisen}, {Dirk J.} and {van Gilst}, {Wiek H.} and Hillege, {Hans L.}",

year = "2015",

month = may,

doi = "10.1016/j.ahj.2014.12.016",

language = "English",

volume = "169",

pages = "693--701",

journal = "American Heart Journal",

issn = "0002-8703",

publisher = "MOSBY-ELSEVIER",

number = "5",

}

Schroten, NF, Damman, K, Hemmelder, MH, Voors, AA , Navis, G, Gaillard, CAJM, van Veldhuisen, DJ , van Gilst, WH & Hillege, HL 2015, 'Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)', American Heart Journal, vol. 169, no. 5, pp. 693-701. https://doi.org/10.1016/j.ahj.2014.12.016

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction). / Schroten, Nicolas F.; Damman, Kevin; Hemmelder, Marc H. et al.
In: American Heart Journal, Vol. 169, No. 5, 05.2015, p. 693-701.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)

AU - Schroten, Nicolas F.

AU - Damman, Kevin

AU - Hemmelder, Marc H.

AU - Voors, Adriaan A.

AU - Navis, Gerjan

AU - Gaillard, Carlo A. J. M.

AU - van Veldhuisen, Dirk J.

AU - van Gilst, Wiek H.

AU - Hillege, Hans L.

PY - 2015/5

Y1 - 2015/5

N2 - AIMS: We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals.METHODS AND RESULTS: Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007).CONCLUSIONS: Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction.

AB - AIMS: We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals.METHODS AND RESULTS: Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007).CONCLUSIONS: Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction.

KW - CONVERTING-ENZYME-INHIBITION

KW - CARDIORENAL END-POINTS

KW - PROGNOSTIC VALUE

KW - MYOCARDIAL-INFARCTION

KW - RANDOMIZED-TRIAL

KW - KIDNEY-FUNCTION

KW - BASE-LINE

KW - VAL-HEFT

KW - MORTALITY

KW - METAANALYSIS

U2 - 10.1016/j.ahj.2014.12.016

DO - 10.1016/j.ahj.2014.12.016

M3 - Article

C2 - 25965717

SN - 0002-8703

VL - 169

SP - 693

EP - 701

JO - American Heart Journal

JF - American Heart Journal

IS - 5

ER -

Schroten NF, Damman K, Hemmelder MH, Voors AA , Navis G, Gaillard CAJM et al. Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction). American Heart Journal. 2015 May;169(5):693-701. doi: 10.1016/j.ahj.2014.12.016