Dataset Information

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.

SUBMITTER: Vaduganathan M

PROVIDER: S-EPMC6676477 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Vaduganathan Muthiah M Cheema Baljash B Cleveland Erin E Sankar Kamya K Subacius Haris H Fonarow Gregg C GC Solomon Scott D SD Lewis Eldrin F EF Greene Stephen J SJ Maggioni Aldo P AP Böhm Michael M Zannad Faiez F Butler Javed J Gheorghiade Mihai M

European journal of heart failure 20171116 4

<h4>Aims</h4>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.<h4>Methods and results</h4>This pre-specified neurohormonal substudy of ASTRONAUT analysed all patients hospitalized for HF with ejection ...[more]

PMID: 29143416

Similar Datasets

Project description:BackgroundFew contemporary data exist evaluating care patterns and outcomes in heart failure (HF) across the spectrum of kidney function.ObjectivesThis study sought to characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction.MethodsGuideline-directed medical therapies were evaluated among patients hospitalized with HF at 418 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry from 2014 to 2019 by discharge CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)-derived estimated glomerular filtration rate (eGFR). We additionally evaluated the risk-adjusted association of admission eGFR with in-hospital mortality.ResultsAmong 365,494 hospitalizations (age 72 ± 15 years, left ventricular ejection fraction [EF]: 43 ± 17%), median discharge eGFR was 51 ml/min/1.73 m2 (interquartile range: 34 to 72 ml/min/1.73 m2), 234,332 (64%) had eGFR <60 ml/min/1.73 m2, and 18,869 (5%) were on dialysis. eGFR distribution remained stable from 2014 to 2019. Among 157,439 patients with HF with reduced EF (≤40%), discharge guideline-directed medical therapies, including beta-blockers, were lowest in discharge eGFR <30 mL/min/1.73 m2 or dialysis (p < 0.001). "Triple therapy" with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor + beta-blocker + mineralocorticoid receptor antagonist was used in 38%, 33%, 25%, 15%, 5%, and 3% for eGFR ≥90, 60 to 89, 45 to 59, 30 to 44, <30 ml/min/1.73 m2, and dialysis, respectively; p < 0.001. Mortality was higher in a graded fashion at lower admission eGFR groups (1.1%, 1.5%, 2.0%, 3.0%, 5.0%, and 4.2%, respectively; p < 0.001). Steep covariate-adjusted associations between admission eGFR and mortality were observed across EF subgroups, but was slightly stronger for HF with reduced EF compared with HF with mid-range or preserved EF (pinteraction = 0.045).ConclusionsDespite facing elevated risks of mortality, patients with comorbid HF with reduced EF and kidney disease are not optimally treated with evidence-based medical therapies, even at levels of eGFR where such therapies would not be contraindicated by kidney dysfunction. Further efforts are required to mitigate risk in comorbid HF and kidney disease.

Project description:AimsTroponin levels are commonly elevated among patients hospitalized for heart failure (HF), but the prevalence and prognostic significance of early post-discharge troponin elevation are unclear. This study sought to describe the frequency and prognostic value of pre-discharge and post-discharge troponin elevation, including persistent troponin elevation from the inpatient to outpatient settings.Methods and resultsThe ASTRONAUT trial (NCT00894387; http://www.clinicaltrials.gov) enrolled hospitalized HF patients with ejection fraction ≤40% and measured troponin I prior to discharge (i.e. study baseline) and at 1-month follow-up in a core laboratory (elevation defined as >0.04 ng/mL). This analysis included 1469 (91.0%) patients with pre-discharge troponin data. Overall, 41.5% and 29.9% of patients had elevated pre-discharge [median: 0.09 ng/mL; interquartile range (IQR): 0.06-0.19 ng/mL] and 1-month (median: 0.09 ng/mL; IQR: 0.06-0.15 ng/mL) troponin levels, respectively. Among patients with pre-discharge troponin elevation, 60.4% had persistent elevation at 1 month. After adjustment, pre-discharge troponin elevation was not associated with 12-month clinical outcomes. In contrast, 1-month troponin elevation was independently predictive of increased all-cause mortality [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.18-2.13] and cardiovascular mortality or HF hospitalization (HR 1.28, 95% CI 1.03-1.58) at 12 months. Associations between 1-month troponin elevation and outcomes were similar among patients with newly elevated (i.e. normal pre-discharge) and persistently elevated levels (interaction P ≥ 0.16). The prognostic value of 1-month troponin elevation for 12-month mortality was driven by a pronounced association among patients with coronary artery disease (interaction P = 0.009).ConclusionsIn this hospitalized HF population, troponin I elevation was common during index hospitalization and at 1-month follow-up. Elevated troponin I level at 1 month, but not pre-discharge, was independently predictive of increased clinical events at 12 months. Early post-discharge troponin I measurement may offer a practical means of risk stratification and should be investigated as a therapeutic target.

Project description:ObjectivesThe purpose of this study was to evaluate in-hospital outcomes among patients with a history of heart failure (HF) hospitalized with coronavirus disease-2019 (COVID-19).BackgroundCardiometabolic comorbidities are common in patients with severe COVID-19. Patients with HF may be particularly susceptible to COVID-19 complications.MethodsThe Premier Healthcare Database was used to identify patients with at least 1 HF hospitalization or 2 HF outpatient visits between January 1, 2019, and March 31, 2020, who were subsequently hospitalized between April and September 2020. Baseline characteristics, health care resource utilization, and mortality rates were compared between those hospitalized with COVID-19 and those hospitalized with other causes. Predictors of in-hospital mortality were identified in HF patients hospitalized with COVID-19 by using multivariate logistic regression.ResultsAmong 1,212,153 patients with history of HF, 132,312 patients were hospitalized from April 1, 2020, to September 30, 2020. A total of 23,843 patients (18.0%) were hospitalized with acute HF, 8,383 patients (6.4%) were hospitalized with COVID-19, and 100,068 patients (75.6%) were hospitalized with alternative reasons. Hospitalization with COVID-19 was associated with greater odds of in-hospital mortality as compared with hospitalization with acute HF; 24.2% of patients hospitalized with COVID-19 died in-hospital compared to 2.6% of those hospitalized with acute HF. This association was strongest in April (adjusted odds ratio [OR]: 14.48; 95% confidence interval [CI]:12.25 to 17.12) than in subsequent months (adjusted OR: 10.11; 95% CI: 8.95 to 11.42; pinteraction <0.001). Among patients with HF hospitalized with COVID-19, male sex (adjusted OR: 1.26; 95% CI: 1.13 to 1.40) and morbid obesity (adjusted OR: 1.25; 95% CI: 1.07 to 1.46) were associated with greater odds of in-hospital mortality, along with age (adjusted OR: 1.35; 95% CI: 1.29 to 1.42 per 10 years) and admission earlier in the pandemic.ConclusionsPatients with HF hospitalized with COVID-19 are at high risk for complications, with nearly 1 in 4 dying during hospitalization.

Project description:BackgroundBlack patients have higher rates of hospitalization for acute heart failure than other race/ethnic groups. We sought to determine whether diuretic efficiency is associated with racial differences in risk for rehospitalization after acute heart failure.MethodsA post hoc analysis was performed on 721 subjects (age, 68±13 years; 22% black) enrolled in 3 acute heart failure clinical trials: ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure), DOSE-AHF (Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure), and CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Repeated-measures ANOVA was used to test for a race×time effect on measures of decongestion. Diuretic efficiency was calculated as net fluid balance per total furosemide equivalents. In a subset of subjects, Cox regression was used to examine the association between race and rehospitalization according to plasma renin activity (PRA).ResultsCompared with nonblack patients, black patients were younger and more likely to have nonischemic heart failure. During the first 72 to 96 hours, there was greater fluid loss (P=0.001), decrease in NT-proBNP (N-terminal pro-B-type natriuretic peptide; P=0.002), and lower levels of PRA (P<0.0001) in black patients. Diuretic efficiency was higher in black than in nonblack patients (403 [interquartile range, 221-795] versus 325 [interquartile range, 154-698]; P=0.014). However, adjustment for baseline PRA attenuated the association between black race and diuretic efficiency. Over a median follow-up of 68 (interquartile range, 56-177) days, there was an increased risk of all-cause and heart failure-specific rehospitalization in nonblack patients with increasing levels of PRA, while the risk of rehospitalization was relatively constant across levels of PRA in black patients.ConclusionsHigher diuretic efficiency in black patients with acute heart failure may be related to racial differences in activity of the renin-angiotensin-aldosterone system.

Dataset Information

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

Aims

Methods and results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets