Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction

Scott D Solomon; Sung Hee Shin; Amil Shah; Hicham Skali; Akshay Desai; Lars Kober; Aldo P Maggioni; Jean L Rouleau; Roxzana Y Kelly; Allen Hester; John J V McMurray; Marc A Pfeffer; Aliskiren Study in Post-MI Patients to Reduce Remodeling (ASPIRE) Investigators

doi:http://dx.doi.org/10.1093/eurheartj/ehq522

Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction

Scott D Solomon, Sung Hee Shin, Amil Shah, Hicham Skali, Akshay Desai, Lars Kober, Aldo P Maggioni, Jean L Rouleau, Roxzana Y Kelly, Allen Hester, John J V McMurray, Marc A Pfeffer, Aliskiren Study in Post-MI Patients to Reduce Remodeling (ASPIRE) Investigators

120 Citationer (Scopus)

Abstract

Aims Direct renin inhibitors provide an alternative approach to inhibiting the reninangiotensinaldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infarction receiving stable, individually optimized therapy, including another inhibitor of the RAAS. Methods and resultsWe randomly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infarction, with the left ventricular ejection fraction (LVEF) ≤45%, and regional wall motion abnormalities (≥20% akinetic area), to receive aliskiren (n = 423), titrated to 300 mg, or matched placebo (n = 397), added to the standard therapy. All patients were required to be on a stable dose of an ACE-inhibitor or ARB, and beta-blocker unless contraindicated or not tolerated. Echocardiograms were obtained at baseline, and following 26-36 weeks of treatment. The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks, and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group. We observed no difference in the primary endpoint of end-systolic volume change between patients randomized to aliskiren (-4.4 ± 16.8 mL) or placebo (-3.5 ± 16.3 mL), or in secondary measures of end-diastolic volume, or LVEF. We also observed no differences in a composite endpoint of cardiovascular death, hospitalization for heart failure, or reduction in LVEF >6 points. There were more investigator reported adverse events in the aliskiren group, including hypotension, increases in creatinine and hyperkalaemia. Conclusion Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects. These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients.

Originalsprog	Engelsk
Tidsskrift	European Heart Journal (English Edition)
Vol/bind	32
Udgave nummer	10
Sider (fra-til)	1227-34
Antal sider	8
ISSN	0195-668X
DOI	https://doi.org/10.1093/eurheartj/ehq522
Status	Udgivet - maj 2011

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http://dx.doi.org/10.1093/eurheartj/ehq522

Citationsformater

Solomon, S. D., Shin, S. H., Shah, A., Skali, H., Desai, A., Kober, L., Maggioni, A. P., Rouleau, J. L., Kelly, R. Y., Hester, A., McMurray, J. J. V., Pfeffer, M. A., & Aliskiren Study in Post-MI Patients to Reduce Remodeling (ASPIRE) Investigators (2011). Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction. European Heart Journal (English Edition), 32(10), 1227-34. https://doi.org/10.1093/eurheartj/ehq522

Solomon, SD, Shin, SH, Shah, A, Skali, H, Desai, A, Kober, L, Maggioni, AP, Rouleau, JL, Kelly, RY, Hester, A, McMurray, JJV, Pfeffer, MA & Aliskiren Study in Post-MI Patients to Reduce Remodeling (ASPIRE) Investigators 2011, 'Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction', European Heart Journal (English Edition), bind 32, nr. 10, s. 1227-34. https://doi.org/10.1093/eurheartj/ehq522

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title = "Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction",

abstract = "Aims Direct renin inhibitors provide an alternative approach to inhibiting the reninangiotensinaldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infarction receiving stable, individually optimized therapy, including another inhibitor of the RAAS. Methods and resultsWe randomly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infarction, with the left ventricular ejection fraction (LVEF) ≤45%, and regional wall motion abnormalities (≥20% akinetic area), to receive aliskiren (n = 423), titrated to 300 mg, or matched placebo (n = 397), added to the standard therapy. All patients were required to be on a stable dose of an ACE-inhibitor or ARB, and beta-blocker unless contraindicated or not tolerated. Echocardiograms were obtained at baseline, and following 26-36 weeks of treatment. The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks, and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group. We observed no difference in the primary endpoint of end-systolic volume change between patients randomized to aliskiren (-4.4 ± 16.8 mL) or placebo (-3.5 ± 16.3 mL), or in secondary measures of end-diastolic volume, or LVEF. We also observed no differences in a composite endpoint of cardiovascular death, hospitalization for heart failure, or reduction in LVEF >6 points. There were more investigator reported adverse events in the aliskiren group, including hypotension, increases in creatinine and hyperkalaemia. Conclusion Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects. These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients.",

author = "Solomon, {Scott D} and Shin, {Sung Hee} and Amil Shah and Hicham Skali and Akshay Desai and Lars Kober and Maggioni, {Aldo P} and Rouleau, {Jean L} and Kelly, {Roxzana Y} and Allen Hester and McMurray, {John J V} and Pfeffer, {Marc A} and K{\o}ber, {Lars Valeur}",

year = "2011",

month = may,

doi = "http://dx.doi.org/10.1093/eurheartj/ehq522",

language = "English",

volume = "32",

pages = "1227--34",

journal = "European Heart Journal",

issn = "0195-668X",

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}

TY - JOUR

T1 - Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction

AU - Solomon, Scott D

AU - Shin, Sung Hee

AU - Shah, Amil

AU - Skali, Hicham

AU - Desai, Akshay

AU - Kober, Lars

AU - Maggioni, Aldo P

AU - Rouleau, Jean L

AU - Kelly, Roxzana Y

AU - Hester, Allen

AU - McMurray, John J V

AU - Pfeffer, Marc A

AU - Aliskiren Study in Post-MI Patients to Reduce Remodeling (ASPIRE) Investigators

PY - 2011/5

Y1 - 2011/5

N2 - Aims Direct renin inhibitors provide an alternative approach to inhibiting the reninangiotensinaldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infarction receiving stable, individually optimized therapy, including another inhibitor of the RAAS. Methods and resultsWe randomly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infarction, with the left ventricular ejection fraction (LVEF) ≤45%, and regional wall motion abnormalities (≥20% akinetic area), to receive aliskiren (n = 423), titrated to 300 mg, or matched placebo (n = 397), added to the standard therapy. All patients were required to be on a stable dose of an ACE-inhibitor or ARB, and beta-blocker unless contraindicated or not tolerated. Echocardiograms were obtained at baseline, and following 26-36 weeks of treatment. The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks, and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group. We observed no difference in the primary endpoint of end-systolic volume change between patients randomized to aliskiren (-4.4 ± 16.8 mL) or placebo (-3.5 ± 16.3 mL), or in secondary measures of end-diastolic volume, or LVEF. We also observed no differences in a composite endpoint of cardiovascular death, hospitalization for heart failure, or reduction in LVEF >6 points. There were more investigator reported adverse events in the aliskiren group, including hypotension, increases in creatinine and hyperkalaemia. Conclusion Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects. These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients.

AB - Aims Direct renin inhibitors provide an alternative approach to inhibiting the reninangiotensinaldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infarction receiving stable, individually optimized therapy, including another inhibitor of the RAAS. Methods and resultsWe randomly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infarction, with the left ventricular ejection fraction (LVEF) ≤45%, and regional wall motion abnormalities (≥20% akinetic area), to receive aliskiren (n = 423), titrated to 300 mg, or matched placebo (n = 397), added to the standard therapy. All patients were required to be on a stable dose of an ACE-inhibitor or ARB, and beta-blocker unless contraindicated or not tolerated. Echocardiograms were obtained at baseline, and following 26-36 weeks of treatment. The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks, and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group. We observed no difference in the primary endpoint of end-systolic volume change between patients randomized to aliskiren (-4.4 ± 16.8 mL) or placebo (-3.5 ± 16.3 mL), or in secondary measures of end-diastolic volume, or LVEF. We also observed no differences in a composite endpoint of cardiovascular death, hospitalization for heart failure, or reduction in LVEF >6 points. There were more investigator reported adverse events in the aliskiren group, including hypotension, increases in creatinine and hyperkalaemia. Conclusion Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects. These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients.

U2 - http://dx.doi.org/10.1093/eurheartj/ehq522

DO - http://dx.doi.org/10.1093/eurheartj/ehq522

M3 - Journal article

SN - 0195-668X

VL - 32

SP - 1227

EP - 1234

JO - European Heart Journal

JF - European Heart Journal

IS - 10

ER -

Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction

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