The effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial

doi:10.1016/j.ahj.2018.03.019

American Heart Journal

Volume 201, July 2018, Pages 164-167

https://doi.org/10.1016/j.ahj.2018.03.019 Get rights and content

In older patients (70 ± 7 years) with chronic well-compensated heart failure with preserved ejection and controlled blood pressure, 6 months treatment with aliskiren (direct renin inhibitor) showed non-significant trends for modest improvements in peak exercise oxygen consumption (14.9 ± 0.2 mL kg⁻¹ min⁻¹ versus 14.4 ± 0.2 mL kg⁻¹ min⁻¹; P = .10, trend) and ventilatory anaerobic threshold (888 ± 19 mL/min versus 841 ± 18 mL/min; P = .08).

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The p-values for peak VO₂ (0.10) and for VAT (0.08) suggest the study may have been underpowered, particularly for the effect size we observed which was less than our sample size estimate. We performed additional analyses which indicated that if the number of completed patients in the trial had been 119, and other results remained the same (such as effect size and variability), then the study would have been positive on peak VO₂ at the 0.05 level of significance. Of course, that includes some

Acknowledgements / potential conflicts of interest

In addition to partial funding for the present study from Novartis (which had no role in study conduct, data analysis, interpretation, or manuscript generation), Dr. KItzman reports the following potential financial conflicts of interest: Consultant for Abbvie, Bayer, Merck, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer-Ingelheim, GSK, and Actavis, current research grant funding from Novartis, Bayer, and GSK, and stock ownership in Gilead Sciences. Dr. Upadhya has received research

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Patients with chronic kidney disease (CKD) and coincident heart failure with preserved ejection fraction (HFpEF) may constitute a distinct HFpEF phenotype. Osteopontin (OPN) is a biomarker of HFpEF and predictive of disease outcome. We recently reported that OPN blockade reversed hypertension, mitochondrial dysfunction, and kidney failure in Col4a3^−/− mice, a model of human Alport syndrome.
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OGDHL mRNA and protein were quantified in myocardial samples from patients with HFpEF, heart failure with reduced ejection fraction, and donor control subjects. OGDHL expression was quantified in hiPS-CMs treated with or without anti-OPN antibody. Cardiac parameters were evaluated in Col4a3^−/− mice with and without global OPN knockout or AAV9-mediated delivery of 2-oxoglutarate dehydrogenase-like (Ogdhl) to the heart.
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Col4a3^−/− mice present a model of HFpEF secondary to CKD wherein OPN and OGDHL are intermediates, and possibly therapeutic targets.
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: ClinicalTrials.gov Identifier: NCT00982033.

: Funding Sources: This study was funded, in part, by an investigator-initiated grant from Novartis Pharmaceuticals. However, Novartis had no role in study conduct, data analysis, interpretation, or manuscript generation. Also funded in part by: NIH R01AG18915 and R01AG045551; The Claude D. Pepper Older Americans Independence Center of Wake Forest University NIH P30AG21332; Clinical and Translational Science Institute of Wake Forest School of Medicine NIH UL1TR001420; and the Kermit G. Phillips II Chair in Cardiovascular Medicine of Wake Forest School of Medicine.

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Research LetterThe effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial

Section snippets

Limitations

Acknowledgements / potential conflicts of interest

J Am Coll Cardiol

Am J Cardiol

Renal protective effects of aliskiren beyond its antihypertensive property in a mouse model of progressive fibrosis

Am J Hypertens

A randomized, controlled, double-blinded trial of enalapril in older patients with heart failure and preserved ejection fraction; effects on exercise tolerance, and arterial distensibility

Circ Heart Fail

Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: a randomised clinical trial

JAMA

A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure

N Engl J Med

Research Letter
The effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial