Plasma renin activity, response to aliskiren, and clinical outcomes in patients hospitalized for heart failure: the ASTRONAUT trial.

Abstract

AIMS:

The direct renin inhibitor, aliskiren, is known to reduce plasma renin activity (PRA), but whether the efficacy of aliskiren varies based on an individual's baseline PRA in patients hospitalized for heart failure (HF) is presently unknown. We characterized the prognostic value of PRA and determined if this risk is modifiable with use of aliskiren.

METHODS AND RESULTS:

This pre-specified neurohormonal substudy of ASTRONAUT analysed all patients hospitalized for HF with ejection fraction (EF) ≤40% with available baseline PRA data (n = 1306, 80.9%). Risk associated with baseline PRA and short-term changes in PRA from baseline to 1 month was modelled with respect to 12-month clinical events. Median baseline PRA was 3.0 (interquartile range 0.6-16.4) ng/mL/h. Aliskiren significantly reduced PRA early after treatment initiation through 12-month follow-up compared with placebo (P < 0.001). The lowest baseline PRA quartile (<0.6 ng/mL/h) was independently predictive of lower all-cause mortality [adjusted hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.81] and the composite of cardiovascular mortality and HF hospitalization (adjusted HR 0.57, 95% CI 0.40-0.79). Delta log-normalized PRA (from baseline to 1 month) was not predictive of either primary endpoint at 12 months (P ≥ 0.43). The prognostic value of baseline PRA and short-term changes in PRA did not vary by randomization to aliskiren or placebo (interaction P ≥ 0.13).

CONCLUSIONS:

Plasma renin activity is reduced early and durably by aliskiren, but this did not translate into improved clinical outcomes in ASTRONAUT. Baseline PRA or short-term reduction in PRA do not identify a subgroup who may preferentially benefit from direct renin inhibition. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387.

• Authors: Muthiah Vaduganathan, Baljash Cheema, Erin Cleveland, Kamya Sankar, Haris Subacius, Gregg C Fonarow, Scott D Solomon, Eldrin F Lewis, Stephen J Greene, Aldo P Maggioni, Michael Böhm, Faiez Zannad, Javed Butler, Mihai Gheorghiade
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 20 Issue 4 Pg. 677-686 (04 2018) ISSN: 1879-0844 [Electronic] England
• PMID: 29143416 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Chemical References

• Amides
• Fumarates
• aliskiren
• Renin

Topics

• Aged
• Amides (administration & dosage)
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Fumarates (administration & dosage)
• Heart Failure (blood, drug therapy, physiopathology)
• Humans
• Inpatients
• Male
• Middle Aged
• Prospective Studies
• Renin (blood, drug effects)
• Renin-Angiotensin System (drug effects)
• Stroke Volume (physiology)
• Treatment Outcome